Untitled Flashcards Set

Levels of organization in body: 

1. Chemical level

• various atoms and molecules make up the body 

2. Cellular level

• cells are the basic units of life

3. Tissue level 

• tissues are groups of cells of similar specialization

• four primary types: muscle, nervous, epithelial, and connective

4. Organ level

• an organ is a unit made up of several tissue types

5. Body system level 

• a body system is a collection of related organs 

6. Organism level

• the body systems are packaged into a functional whole body 

What is lumen?

• A lumen is the cavity within a hollow organ or tube – like the digestive tract lumen

Know properties and examples of epithelial tissue, connective tissue, exocrine glands, endocrine glands.

1. Epithelial tissue

• Consists of cells specialized for exchanging materials between the cell and its environment

• Any substance that enters or leaves the body must cross an epithelial barrier

• Epithelial tissue is organized into two types of structures: epithelial sheets and secretory glands 

• Ex. the outer layer of the skin is epithelial tissue, as is the lining of the digestive tract 

• Membrane cell junctions: tight junction and desmosome are in the epithelial tissue

2. Connective tissue

• Connective tissue connects, supports, and anchors various body parts

• By having relatively few cells dispersed within an abundance of extracellular material 

• Ex. the loose connective tissue that attaches epithelial tissue to underlying structures; tendons, which attach skeletal muscles to bones; bone, which gives the body shape, support, and protection; and blood, which transports materials from one part of the body to another.

Glands are made up of epithelial tissue specialized for secreting.

There are two types of glands:

1. Exocrine glands

• Secrete through ducts to the outside of the body 

• (exo means “external”; crine means “secretion”)

• Ex. sweat glands and glands that secrete digestive juices

2. Endocrine glands

• Lack ducts and release their secretory products, known as hormones, internally into the blood

• (endo means “internal”; crine means “secretion”)

• Ex. the pancreas secretes insulin into the blood, which transports this hormone to its sites of action throughout the body. Most cell types depend on insulin for taking up glucose (sugar)

1. Homeostasis : processes to maintain a relatively stable internal environment 

2. Intracellular fluid (ICF) :  the fluid inside of our cells 

3. Extracellular fluid (ECF) :  the fluid outside of our cells 

   1. Plasma is one compartment of extracellular fluid 

   2. Interstitial fluid (IF) 

   3. (Transcellular fluid) - isolated pockets of ECF 

What is the “internal environment” which is maintained in homeostasis? 

• Both interstitial fluid (IF) and plasma 

Two main compartments of the ECF:

1. Plasma is one compartment of extracellular fluid 

2. Interstitial fluid (IF) 

Third smaller compartment of ECF:

3. (Transcellular fluid) - isolated pockets of ECF 

In which compartment (ECF vs. ICF) is sodium concentration high? In which compartment is potassium concentration high?

High sodium outside the cell — low sodium inside 

High potassium inside the cell — low potassium outside 

* Sodium and potassium are always opposite… if its high sodium outside, the potassium is opposite

Control Systems

1. Negative feedback (self-regulating)

• Negative feedback is the most common. 

• In negative feedback, the response moves the variable in the opposite direction of the stimulus. 

• In negative feedback, a control system’s output is regulated to resist change so that the controlled variable is kept at a relatively steady set point. 

Example of negative feedback (including set point, effector, sensors (receptors), integrating center):

• A common example of negative feedback is control of room temperature. Room temperature is a controlled variable, a factor that can vary but is held within a narrow range by a control system. In our example, the control system includes a thermostat, a furnace, and all their electrical connections. The room temperature is determined by the activity of the furnace, a heat source that can be turned on or off. To switch on or off appropriately, the control system as a whole must “know” what the actual room temperature is, “compare” it with the desired room temperature, and “adjust” the output of the furnace to bring the actual temperature to the desired level. A thermometer in the thermostat provides information about the actual room temperature. The thermometer is the sensor, which monitors the magnitude of the controlled variable. The sensor typically converts the original information regarding a change into a “language” the control system can “understand.” For example, the thermometer converts the magnitude of the air temperature into electrical impulses. This message serves as the input into the control system. The thermostat setting provides the desired temperature level, or set point. The thermostat acts as an integrator, or control center: It compares the sensor’s input with the set point and adjusts the heat output of the furnace to bring about the appropriate response to oppose a deviation from the set point. The furnace is the effector, the component of the control system commanded to bring about the desired effect. 

• These general components of a negative-feedback control system are summarized:

2. Positive feedback ( “self-propagating”  and self-amplifying” )

• The output enhances or amplifies a change so that the controlled variable continues to move in the direction of the initial change.

• Ex. the heat generated by a furnace triggering the thermostat to call for even more heat output from the furnace so that the room temperature continuously rises.

• Because the major goal in the body is to maintain stable, homeostatic conditions, positive feedback does not occur nearly as often as negative feedback.

3. Feedforward control (anticipatory) 

• Initiates responses in anticipation of a change 

Afferent pathway, efferent pathway. 

• The sensory receptor (receptor for short) responds to a stimulus, which is a detectable change in the environment of the receptor. In response to the stimulus, the receptor produces an action potential that is relayed by the afferent pathway to the integrating center (usually the CNS) for processing. The integrating center processes all information available to it from this receptor, and from all other inputs, and then “makes a decision” about the appropriate response. The instructions from the integrating center are transmitted via the efferent pathway to the effector organ—a muscle or gland—that carries out the desired response.

Homeostatic control systems can be grouped into two classes: 

1. Intrinsic controls (local)

• Built into or are inherent in an organ (intrinsic means “within”). 

• Intrinsic controls serve only the organ in which they occur

2. Extrinsic controls (systemic)

• Most factors in the internal environment are maintained by extrinsic controls

• Regulatory mechanisms initiated outside an organ to alter the organ’s activity (extrinsic means “outside of ”)

• Extrinsic control permits coordinated regulation of several organs toward a common goal

Thermoregulation in the body: 

Where is the body’s thermoregulation center (thermostat)? 

• Hypothalamus regulates body temperature 

Where are the body’s thermoreceptors, and what does each type specifically monitor? 

1. Central thermoreceptors 

• Central thermoreceptors monitor core temperature 

• Located in the hypothalamus, abdominal organs, elsewhere 

2. Peripheral thermoreceptors

• Peripheral thermoreceptors monitor skin temperature throughout the body

• Located in the skin 

What are the effectors? 

• The component of the control system commanded to bring about the desired effect

• In the response loop for controlling body temperature… when you are sweating, what is the effector? 

  • The effector is sweat glands

Explain the body’s response to cold exposure and a decrease in core body temperature. 

What if thermoreceptors detect temp. too low? 

• → shivering

• → vasoconstriction in skin (and relatively dilated blood vessels in core) 

• → (goosebumps)

Processes to create a fever:

• Brain (thermostat went up for the brain) (38 degrees)

• But blood remains the same temp (37 degrees)

• The hypothalamus thinks you’re too cold → so shivering to generate heat 

• Vasoconstriction in the skin (less blood going to the surface to retain the heat)

• This will bring your blood up to 38 degrees 

• The fever is created for the blood to match the temp in the brain 

What is non-shivering thermogenesis, and where in the body does this process occur? (contrast the role of the mitochondrion in this process to the role of the mitochondrion in glucose metabolism such as in Question #9 below.) 

Explain the body’s response to heat exposure and an increase in core body temperature. 

What if temp. too high? 

→ sweating 

→ vasodilation in skin (to redirect blood flow) 

In the response loop for controlling body temperature… when you are sweating, what is the effector? 

→ Body temperature is high which activates sweat glands (the effector) 

Processes to reduce a fever: 

• Sweating (gets rid of the heat and bring temperature down) 

• Increased blood flow to the skin so the heat can escape 

• Body temperature is one example of a controlled variable.

Pyrogens 

• Reset set point in hypothalamus 

(“turn up the thermostat”)

• Pyrogens are setting you up to have a fever 

Q:       Where do pyrogens come from? 

A:  -    From certain bacterial infections 

(exogenous pyrogens)

• From certain types of somatic cells, such as macrophages 

(endogenous pyrogens)

Processes to create a fever:

• Brain (thermostat went up for the brain) (38 degrees)

• But blood remains the same temp (37 degrees)

• The hypothalamus thinks you’re too cold → so shivering to generate heat 

• Vasoconstriction in the skin (less blood going to the surface to retain the heat)

• This will bring your blood up to 38 degrees 

• The fever is created for the blood to match the temp in the brain 

Heat and Cold Related Disorders

1. Heat exhaustion

• A state of collapse, usually manifested by fainting; profuse sweating

• Caused by reduced blood pressure brought about as a result of overtaxing the heat-loss mechanisms

• Heat exhaustion serves as a safety valve to help prevents heat stroke 

2. Heat stroke

• Failure of the temperature control center in the hypothalamus; hot, dry skin

3. Hypothermia 

• A fall in body temperature, occurs when generalized cooling of the body exceeds the ability of the normal heat-producing and heat-conserving regulatory mechanisms to match the excessive heat loss

4. Hyperthermia 

• Rapidly rising body temperature 

• No sweating occurs, despite a markedly elevated body temperature, because the hypothalamic thermoregulatory control centers are not functioning properly and cannot initiate heat-loss mechanisms

Control of Blood Sugar  (from lecture, pp. 689-699, and lecture slides)

Which molecule is “blood sugar”? 

• Glucose is “blood sugar”

In humans, which complex carbohydrate is the storage form for this blood sugar?

• The complex carbohydrate that acts as the storage form for glucose is Glycogen.  

The island of cells (purple clumps) is called an Islet of Langerhans.

Islet of Langerhans

When blood sugar is too high: 

• Beta cells secrete insulin,

a hormone, which then acts on any target cell which has receptors for insulin 

( a hormone is a signal molecule that’s released into the bloodstream; the blood carries it all throughout the body )

When blood sugar is too low: 

• alpha cells secrete glucagon, a hormone 

***tip to remember : glucagon is when glucose is gone  

What is the role of insulin? 

• Insulin lowers blood glucose

• Insulin is controlled by negative-feedback

Three prime examples of target cells for insulin:

1. Liver cells

2. Skeletal muscle cells

3. Adipose tissue 

Three prime examples of target cells for insulin:

1. Liver cells

• Liver stores glucose from blood as glycogen

2. Skeletal muscle cells

• Skeletal muscle cells store glycogen and build protein 

3. Adipose tissue 

• Adipose tissue uses glucose from blood to form fat 

End result: Glucose level drops to maintain homeostasis.  

1. From which cells, and from which organ, does insulin come, and what stimulates its release?

• Insulin comes from:

  • Beta cells 

  • Pancreas

  • When blood sugar is too high it stimulates insulin 

2. Which body cells respond to insulin (and how do these cells “know” that insulin is there)?

1. Liver cells

2. Skeletal muscle cells 

3. Adipose tissue

• These cells know that insulin is there because they have insulin receptors

3. What do the responding cells do when insulin arrives? 

Three prime examples of target cells for insulin:

1. Liver cells

• Liver stores glucose from blood as glycogen

2. Skeletal muscle cells

• Skeletal muscle cells store glycogen and build protein 

3. Adipose tissue 

• Adipose tissue uses glucose from blood to form fat 

End result: Glucose level drops to maintain homeostasis.  

Glucagon

When blood sugar is too low: 

• alpha cells secrete glucagon, a hormone 

***tip to remember : glucagon is when glucose is gone  

Glucagon comes from:

• Alpha cells

• Pancreas (Islet of Langerhans)

• When blood sugar is too low alpha cells secrete glucagon

Two prime examples of target cells for glucagon:

1. Liver cells 

• Liver breaks down glycogen to glucose. Glucose enters blood. 

2. Adipose tissue 

• Adipose tissue breaks down fat 

If you have high glucose, you have to inhibit your alpha cells so you do not produce glucagon. 

Diabetes mellitus 

Common initial symptoms: 

• Excessive urination

• Excessive thirst 

• Very hungry

• Unexplained weight loss

• Very tired 

Type 1 Diabetes  - diagnosed in childhood (not born w)

• autoimmune disease (immune system is attacking your own beta cells - which secrete insulin)

• pancreas does not release insulin

• treatment: insulin injections 

Type 2 Diabetes - most common type of diabetes in the US and globally

• # cases on the rise 

• linked to various risk factors

  • (obesity, sedentary lifestyle, individuals that are POC because of health disparities) 

• body’s target cells (esp. liver and skeletal muscle) are insulin resistant 

• treatment: 

  • lifestyle changes 

  • medications to increase insulin sensitivity, decrease amount of sugar released by liver, etc. 

• may need insulin (because consistently high glucose damages beta cells) 

• cannot be cured, but can be reversed 

Gestational diabetes

• in mom, during pregnancy 

• (once the baby is born, the diabetes goes away)

• risk factors: overweight, family history, previously had a big baby (9 lbs or bigger)

• is a risk factor for developing Type 2 diabetes later on (both mom and baby)

Functions of the following organelles and cell structures:

• Cell membrane – encloses the cells, keeps the ICF within the cells from mingling with the ECF outside the cells 

• Nucleus – contains the cell’s genetic material

• Mitochondrion – generates ATP

• Cytoplasm – the portion of the cell’s interior no occupied by the nucleus 

• Cytoskeleton – interconnected system of protein fibers and tubes 

• Ribosomes – carry out protein synthesis

• Rough ER – synthesizes proteins 

• Smooth ER – does not contains ribosomes, instead it packages new proteins in transport vesicles

• Transport vesicles –carry their cargo to the Golgi complex for further processing

• Golgi complex – (Think Fedex… package and ship from the cell) – packages secretory vesicles for release

• Lysosomes – small, break down organic molecules and remove worn-out organelles

• Secretory vesicles – contains proteins to be secreted

• Peroxisomes – produce and decompose hydrogen peroxide

Adenosine triphosphate (ATP)

• Mitochondria plays a major role in generating ATP

• Consists of adenosine with three phosphate groups attached (tri means “three”)

• When the high-energy bond that binds the terminal phosphate to adenosine is split, a substantial amount of energy is released

• ATP has high energy bonds in it, and the cell can access that energy from the high energy bond 

1.  How does ATP provide energy to the cell? 

• Cells can “cash in” ATP to pay the energy “price” for running the cell machinery

2. How and where does the cell make ATP? 

• The cell makes ATP through cellular respiration within the mitochondrial matrix 

3. What is the relationship between ATP and ADP?

• To obtain immediate usable energy, cells split the terminal phosphate bond of ATP, which yields adenosine diphosphate (ADP)

Stages of Cellular Respiration:

1. Glycolysis – in the cytosol

2. Citric acid cycle – in the mitochondrial matrix

3. Oxidative phosphorylation (electron transport chain) – in the mitochondrial inner membrane

Glucose Metabolism 

    (to provide cells with energy) 

Glucose Metabolism

1. Glycolysis 

2. “Conversion step” 

3. Krebs cycle = citric acid cycle 

        = tricarboxylic acid cycle 

        = TCA cycle 

4. Electron transport chain = oxidative phosphorylation 

1. Glycolysis: 

• Glycolysis is happening in the cytoplasm of a cell 

• 6 carbon glucose molecule to start with, and we end up with 2 pyruvates 

• NADH is carrying high energy electrons

  • The whole point of this is to get energy out of the glucose and pack it into ATP 

• You get 2 ATP from glycolysis 

• Plus, you get 2 NADH

2. Conversion Step:

• Pyruvate goes into the mitochondrial matrix 

• When it goes through the matrix, it's going to be converted into something else 

• The pyruvates get converted to 2 Acetyl CoA

• NADH are holding the high energy electrons 

• 2 CO2

• You get 2 NADH

3. Krebs Cycle: 

• 2 Acetyl CoA go thru the krebs cycle 

• High energy electrons are going to get picked up so we get 6 more NADH’s 

• NADH and FADH2 both pick up high energy electrons 

• 4 CO2 

• One molecule of ATP is generated for each molecule of acetyl-CoA that enters the citric acid cycle, for a total of two molecules of ATP for each molecule of processed glucose

• ( 1 Acetyl CoA = 1 ATP so 2 Acetyl CoA = 2 ATP )

• You get 6 NADH and 2 FADH2

• You get 2 ATP from krebs cycle 

4. Electron Transport Chain (oxidative phosphorylation): 

• Electrons carried by NADH and FADH2 from the matrix → Now entering the inner mitochondrial membrane and cristae 

• The electrons dropped off and going down the chain, and as its going down, the energy is being used to make ATP 

• The energy came from the electron from NADH and FADH2 

• When the electrons make it to the end of the chain, they get collected by oxygen 

• You get 2 FADH2 and 10 NADH

• You get A LOT of ATP from the electron transport chain 

In summary…

• This is directly related to our respiratory system 

• We produce ATP to get picked up by oxygen 

• In this process, gets rid of CO2

What is the purpose of FADH₂ and NADH? 

• FADH₂ and NADH transports electrons from the Krebs cycle and Glycolysis to the electron transport chain 

Which processes stop if there is no oxygen?

• The electron transport chain and the krebs cycle stops if there is no oxygen 

• If no O2 is available, pyruvate is converted to lactate instead of an acetyl group

Which processes release carbon dioxide?

• The Krebs cycle releases carbon dioxide 

Aerobic Metabolism vs. Anaerobic Metabolism 

(oxygen is used) (oxygen is not used) 

Aerobic metabolism (aerobic respiration):

• Glucose metabolism works fine. 

Anaerobic metabolism (no oxygen available): 

• Can’t do the electron transport chain → NADH and FADH2 are stuck holding onto those high energy electrons 

  • If there is no oxygen, the electron transport chain stops. The krebs cycle stops too. 

  • The NADH and the FADH2 are building up. Which means, we don’t have NAD. You need to get rid of the electrons in NADH and FADH2, in order to go back into NAD and FAD →  in order to start up the cycle again. 

• The pyruvate stays out in the cytoplasm and it's going to be used to regenerate NAD. This reaction happens to regenerate NAD!

  • The pyruvate is going to get converted to lactic acid. 

  • In the process of doing this, it uses NADH so we can go back to NAD 

  • Lactate dehydrogenase is the enzyme that converts pyruvate to lactate 

  • It’s a way to keep glycolysis working. But if a cell has to resort to anaerobic metabolism, the disadvantage is that it doesn’t produce as much ATP 

Exam Question: 

What occurs during oxidative phosphorylation (the electron transport chain)? 

1. Each molecule of glucose is broken down to form two molecules of carbon dioxide 

(no glucose in electron transport chain)

2. NAD+ is reduced to NADH 

(this is backwards)

3. ATP is formed in the cytoplasm

(mitochondria)

4. Oxygen donates electrons to power ATP production

(NADH is the ones that donated the electrons, oxygen collects it)

5. None of the above

a) When a cell doesn’t have many mitochondria, what would be the primary purpose for the cell to convert pyruvate to lactate? 

• The primary purpose for the cell to convert pyruvate to lactate is – if no O2 is available, pyruvate is converted to lactate instead of an acetyl group

b) Later, if the cell can make more mitochondria, some of the lactate is converted back to pyruvate. Explain this in terms of the Law of Mass Action.

• If the cell can make more mitochondria, some of the lactate is converted back to pyruvate. According to the law of mass action, if the concentration of one substance involved in a reversible reaction is increased, the reaction is driven toward the opposite side

Functions of the Plasma Membrane:

• Regulate the passage of substances into and out of cells and between cell organelles and cytosol 

• Detect chemical messengers arriving at the cell surface

• Link adjacent cells together by membrane junctions 

• Anchor cells to the extracellular matrix 

Describe the fluid mosaic model of the cell membrane, and the locations and roles of each molecule type: phospholipids, proteins, cholesterol, carbohydrates on glycoproteins or glycolipids. 

“Fluid Mosaic Model of the Cell Membrane” 

Molecular components of cell membrane:

1. Phospholipids (phospholipid bilayer)

• In water, phospholipids self-assemble into a lipid bilayer, a double layer of lipid molecules 

2. Proteins

• Membrane proteins are inserted within or attached to the lipid bilayer

• The fluidity of the lipid bilayer enables many membrane proteins to float freely like “icebergs” in a moving “sea” of lipids. This view of membrane structure is known as the fluid mosaic model, in reference to the membrane fluidity and the ever-changing mosaic pattern of the proteins embedded in the lipid bilayer. 

3. Carbohydrates (on glycoproteins/glycolipids)

• Located on the outer surface of cells, “sugar coating” them

4. Cholesterol  

• Contributes to both the fluidity and the stability of the membrane

• Cholesterol molecules are tucked between the phospholipid molecules

Phospholipid molecule

• Polar heads are hydrophilic

• Nonpolar tails are hydrophobic 

Membrane (cell) Junctions 

1. Tight junction

• proteins (like occludins and claudins) fuse two cells together 

• mainly in epithelial tissue 

• prevents materials from crossing through the extracellular gap 

• forces transport to be transcellular

2. Desmosome 

• allows tissue stretching (mechanical stress) without tearing the cell or tissue 

• e.g., in cardiac muscle tissue (heart)

in epithelial tissue such as epidermis of skin 

and wall of the bladder 

3. Gap junction 

• connexon forms a ‘communicating junction’

• allows water, ions, signal molecules to go from cytoplasm to cytoplasm  

FYI… a tissue can have more than one type of membrane junction

Which cell junction consists of connexons? 

• Gap junction are made up of connexons, which permit passage of ions and small molecules between cells

Which cell junction involves cadherins? 

• Desmosome junction 

Which type of junctions are “communicating junctions”?

• Gap junction are communicating junctions 

Exam Question

Q: Where is the concentration of K+ (potassium) higher?

1. ECF

2. ICF

3. Neither; because of homeostasis, the concentration of K+ is equal in the ECF and the ICF

A: The concentration of K+ is higher in the ICF. 

High sodium outside the cell — low sodium inside 

High potassium inside the cell — low potassium outside 

• If a substance can cross the membrane, the membrane is permeable to that substance

• If a substance cannot pass, the membrane is impermeable to it

• The plasma membrane is selectively/semi permeable: It permits some particles to pass through while excluding others

Concentration gradient

• A difference in concentration of a particular substance between two adjacent areas

Net movement

• The overall direction of particle movement

•  In both areas, individual molecules move randomly and in all directions, but the net movement of molecules by diffusion is from the area of higher concentration to the area of lower concentration.

Equilibrium

• Equilibrium means there is no more net movement 

Membrane transport mechanisms

1. Simple diffusion (high to low, no energy needed)

• solute moves from an area of high concentration of that solute to an area of low concentration of that solute 

• passive process 

“down the concentration gradient” 

• continues until equilibrium (no more net movement)

Variables which affect simple diffusion through the cell membrane: 

      Fick’s Law of Diffusion 

ΔC → concentration gradient 

• bigger concentration gradient, the faster it will go 

A → surface area 

• the bigger the surface area, the higher the rate of diffusion 

𝛽 + the other variables → permeability (P)

• describing how easily can the solute cross the membrane 

𝛽 → partition coefficient 

• a number that indicates how (relatively) lipid soluble the solute is 

(the cell membrane is all lipids) 

experimentally derived: 

partition coefficient number = lipid solubility/water solubility

• the bigger the partition coefficient, the higher the rate of diffusion 

√㎿ → size of solute 

• the bigger the solute, the slower the rate of diffusion

ΔX → distance solute must travel

• the longer the distance is, the slower the rate of diffusion 

if it has to travel farther, it's going to take longer

• the distance is how thick the membrane is

• diffusion is only practical over very short distances, otherwise it takes too long

The slightly negative oxygen is attracted to the positive ion, such as sodium (Na+) or potassium (K+).  Water is polar. It has a hydration shell = a ring of water molecules around it. 

• When it’s picked up water, the hydrated sodium is bigger than the hydrated potassium. 

• They both have the same 1+ charge. 

• However, the positive charge for sodium is in 0.9 angstrom space — a smaller space. Therefore, it attracts a lot of water and you get a larger hydration shell. 

• However, the potassium is in 1.3 angstroms — a bigger space. It is more dilute so it doesn't attract as much water and you get a smaller hydration shell. 

  • Potassium would move faster because it is smaller in size. If it's smaller, the membrane will be more permeable to it and it'll have an easier time crossing. 

Trivia: The cell membrane is 50x more permeable to potassium than to sodium. If everything else was equal, the potassium can go 50x faster than sodium. 

Assuming concentration gradients, etc. are equal, which will move faster across the cell membrane?

1. sodium

2. potassium 

→ potassium would move faster because it is smaller in size

Membrane transport mechanisms

1. Simple diffusion (“diffusion”) 

1. through phospholipid bilayer 

• (very limiting - only a few can get through the phospholipid bilayer, such as O2, CO2, small nonpolar solutes) 

2. through channel proteins 

(for example, for ions to diffuse across membrane)

• open to both sides of the membrane simultaneously (ECF & ICF side)

• specific and selective for what can go through the pipe (ex. only sodium can go through, not any other ion)

1. Simple diffusion 

1. through phospholipid bilayer

2. through channel proteins 

1. leak channels (permanently open) 

• every single cell in the body has leak channels for sodium and potassium

If Na+ is moving through a leak channel, in which direction would it be “leaking”? 

1. Into the cell

2. Out of the cell 

→ Sodium is leaking into the cell. Why? It’s HIGH SODIUM OUTSIDE THE CELL. 

Membrane transport mechanisms

1. Simple diffusion (high to low, no energy needed) 

1. through phospholipid bilayer

2. through channel proteins 

1. leak channels (permanently open) 

2. gated channels (sometimes open, sometimes not) 

• there is something that is regulating whether the gate of the channel is open or closed 

• certain cells have gated channels 

• some gated channels are either: 

ligand-gated (chemically-gated) 

voltage-gated (electrically gated) 

mechanically gated (force or pressure) 

Q: Temperature is another variable which could influence diffusion rate. The higher the temperature, the faster the particles move. Why isn’t temperature listed as one of the variables in Fick’s Law? Why do you think that I didn’t emphasize it as a common variable affection diffusion in the human body? 

• Homeostasis – our body regulates temperature to maintain a relatively stable internal environment so its not a major variable that affects diffusion

Variables which affect simple diffusion through the cell membrane: 

1. Concentration gradient

2. Surface area of membrane 

3. Permeability

4. Partition coefficient

5. Size of solute

6. Distance solute must travel

What is partition coefficient?

• 𝛽 → partition coefficient 

• a number that indicates how (relatively) lipid soluble the solute is 

(the cell membrane is all lipids) 

experimentally derived: 

partition coefficient number = lipid solubility/water solubility

• the bigger the partition coefficient, the higher the rate of diffusion 

During diffusion, either simple or facilitated, the movement of the substance is powered by its own concentration gradient. During active transport, energy input is required to move a substance against its concentration gradient. In direct active transport, ATP hydrolysis directly powers substance movement. In indirect active transport, substance movement is powered by the concentration gradient of another substance.

Only small nonpolar molecules can directly pass through the lipids of the plasma membrane. This type of movement is an example of simple diffusion. Note that simple diffusion occurs only if a concentration gradient exists.

Integral membrane proteins play an important role in the transport of many substances across the membrane. For example, cotransporters are indirect active transport proteins. In a cotransport system, integral membrane proteins move two substances at the same time, using the energy stored in the concentration gradient of one substance to power the movement of a second substance against its concentration gradient. Cotransporters do not use ATP as a power source, as occurs in direct active transport.

Diffusion (based on the particle's own concentration gradient) and electrical forces (based on the total charge concentration gradient) combined determine which way a charged particle will move if the membrane becomes permeable to it. Notice that neither of these processes requires ATP. The two gradients combined constitute the electrochemical gradient.

Week 4 

Name some examples of substances which can undergo simple diffusion directly across the phospholipid bilayer. (Why is it a short list of examples?)

• very limiting - only a few can get through the phospholipid bilayer, such as 

O2, CO2, small nonpolar solutes

Channel Proteins

Membrane transport mechanisms

1. Simple diffusion (“diffusion”) 

1. through phospholipid bilayer

2. through channel proteins 

(for example, for ions to diffuse across membrane)

• open to both sides of the membrane simultaneously (ECF & ICF side)

• specific and selective for what can go through the pipe (ex. only sodium can go through, not any other ion)

1. leak channels (permanently open) 

• every single cell in the body has leak channels for sodium and potassium

2. gated channels (sometimes open, sometimes not) 

• there is something that is regulating whether the gate of the channel is open or closed 

• certain cells have gated channels 

• some gated channels are either: 

ligand-gated (chemically-gated) 

voltage-gated (electrically gated) 

mechanically gated (force or pressure) 

Cystic Fibrosis (CF)

• The most common fatal genetic disease 

• Symptoms are characterized by the production of abnormally thick, sticky mucus — lungs and pancreas 

• CF is caused by one of a number of genetic defects that lead to production of a flawed version of a protein known as cystic fibrosis transmembrane conductance regulator (CFTR)

• Treatment consists of physical therapy and mucus-thinning aerosols to help clear the airways of excess mucus and antibiotic therapy to combat respiratory infections

Channel Protein vs Carrier Protein

1. Channel proteins simply provide a pore for molecules to passively diffuse through without binding to them; open to both sides of the membrane (ICF & ECF) simultaneously

• Channel proteins are specific, selective and cannot get saturated 

2. Carrier proteins are membrane proteins that bind to specific molecules on one side of the cell membrane and then release it on the other side

• Carrier proteins are specific and can get saturated 

Membrane transport mechanisms 

1. Simple diffusion

2. Mediated transport 

• uses a carrier protein (transporter) 

1. only open on one side of membrane at a time 

2. has a binding site(s) for solute

• this transporter can get saturated

Membrane transport mechanisms 

1. Simple diffusion

2. Mediated transport 

1. Facilitated Diffusion 

• uses a carrier protein to shuttle glucose from High to low across the membrane  

• e.g., glucose transport using GLUT 

(GLUT = the name of the carrier protein) 

BUT … if GLUTs get saturated, how can the cell increase glucose transport into the cell, for example, when blood sugar is high? 

Review… 

• Islets of Langerhans 

• When blood sugar is too high: beta cells secrete insulin 

• The beta cells secrete insulin into the blood 

1. One option to increase glucose transport is to ensure that there is still a concentration gradient 

• this occurs in the liver,  GLUT 6 

2. Another option to increase glucose transport is to insert more carrier proteins into the membrane 

• this occurs in the skeletal muscle cells and adipose tissue. There are GLUT 4 proteins that are already made sitting in storage inside the cell, but they're not up in the cell membrane yet. When insulin arrives, that's a signal we need more transporters and the transporters are maxed out and saturated. So… there are more transporters to bring in more glucose. 

Membrane transport mechanisms 

1. Simple diffusion

2. Mediated transport 

1. Facilitated Diffusion 

2. Active transport 

• solute moves against its concentration gradient (“uphill”)

• requires input of energy 

2. Active transport 

1. primary active transport 

(carrier protein uses ATP) 

e.g., sodium-potassium pump = Na+/K+ ATPase pump

• very important carrier protein 

• Sodium-potassium pump is pumping sodium OUT and pumping potassium IN 

• this pump is the reason why its high concentration sodium outside the cell and high potassium inside the cell 

Steps of Sodium-Potassium Pump: 

• Pump picked up 3 sodium ions. ATP is attached to the pump, and when the 3 sodium ions bind, it activates the built in enzyme which CUTS ATP. the ADP floats away, and the phosphate stays attached to the pump. 

• The pump has been phosphorylated. This causes it to change shape and now it drops off the 3 sodium to the outside of the cell. 

• Pumped the 3 sodium ions from LOW to HIGH 

• Now it picks up 2 potassium from the low side, this causes the phosphate to fall off. The pump is dephosphorylated. This causes the pump to change shape and open to the inside of the cell where it drops off 2 potassium. It's now moved 2 potassium from low to high.

• The cycle repeats.

Review: 

• The pump is actively transporting 3 sodium ions outside of the cell, and 2 potassium ions inside of the cell. 3 sodium out, 2 potassium in. 

• Every single cell in the human body has sodium-potassium pumps, working NONSTOP. which is using a LOT of ATP. 

• Every single cell has leak channels for sodium and potassium, but the sodium-potassium pump is always pumping it back in. These are both happening at the same time. 

2. Active transport 

1. primary active transport 

2. secondary active transport 

(carrier protein uses an ion gradient) 

as the sodium goes downhill, the solute gets a ride and goes uphill

symport (cotransport)

antiport (countertransport) 

e.g., secondary active transport of glucose using SGLT

SGLT = sodium glucose transporter

• sodium goes high to low, 

Luminal membrane vs. Basolateral membrane 

***important luminal membrane↓

↑basolateral membrane 

• Having these tight junctions there are also keeping the proteins in the luminal membrane on the luminal side, and keeping the proteins in the basolateral membrane on the basolateral side

• The green structure in the luminal membrane is SGLT (sodium glucose transporter) brings sodium downhill so glucose can go uphill

• The red circle in the basolateral membrane is the sodium potassium pump 

• Yes, SGLT brings in sodium, but the pump is pumping the sodium back out.

• The sodium potassium pump uses ATP, and that is working behind the scenes to maintain a sodium gradient. If the sodium potassium pump stopped working and no longer pumping sodium out of the cell, there would be too much sodium, no high to low balance, so glucose won’t be carried in anymore. 

• The point is to bring the glucose through the membrane 

Which kind of transport is the glucose transport in the figure? (The glucose is going from high to low) 

→ facilitated diffusion, GLUT 

This one cell in the figure has all of these transport mechanisms to accomplish the absorption of glucose:

Passive transport: 

• Simple diffusion (through lipid bilayer & channel protein)

• Osmosis 

• Facilitated diffusion

Active transport:

• Primary active transport

• Secondary active transport (symport or antiport)

• Endocytosis 

Carrier-mediated transport: 

• Facilitated diffusion

• Primary active transport

• Secondary active transport (symport or antiport)

For a particular cell, how can the rate of transport via a specific carrier protein be increased? 

1. Mediated transport 

1. Facilitated Diffusion 

• uses a carrier protein to shuttle glucose from High to low across the membrane  

• e.g., glucose transport using GLUT 

(GLUT = the name of the carrier protein) 

BUT … if GLUTs get saturated, how can the cell increase glucose transport into the cell, for example, when blood sugar is high? 

The rate of glucose transport can be increased through concentration gradient and inserting more carrier proteins into the membrane. 

How do liver cells increase glucose transport?

1. One option to increase glucose transport is to ensure that there is still a concentration gradient 

• this occurs in the liver, GLUT 6 

How does resting skeletal muscle increase glucose transport?

2. Another option to increase glucose transport is to insert more carrier proteins into the membrane 

• this occurs in the skeletal muscle cells and adipose tissue. There are GLUT 4 proteins that are already made sitting in storage inside the cell, but they're not up in the cell membrane yet. When insulin arrives, that's a signal we need more transporters and the transporters are maxed out and saturated. So… there are more transporters to bring in more glucose.

Exercising muscle, glucose transport, & diabetes

• Insulin is not responsible for the increased transport of glucose into exercising muscles, however, because blood insulin levels fall during exercise

• Instead muscle cells insert more glucose carriers in their plasma membranes in direct response to exercise

• Because insulin enhances the facilitated diffusion of glucose into most cells, an exercise-induced increase in insulin sensitivity is one of the factors that makes exercise a beneficial therapy for controlling diabetes 

GLUT (Glucose Transporter) 

• glucose cannot cross plasma membranes on its own because it is not lipid soluble and is too large to fit through a channel

• function of GLUT – glucose carrier molecules that facilitate membrane transport of glucose

• GLUT is used for facilitated diffusion 

Distinguish between GLUT-1, GLUT-2, GLUT-3, and GLUT-4

1. GLUT-1 transports glucose across the blood-brain barrier

2. GLUT-2 transfers into the adjacent bloodstream the glucose that has entered the kidney and intestinal cells by means of the sodium and glucose cotransporter

3. GLUT-3 is the main transporter of glucose into neurons

4. The transporter responsible for glucose uptake by most body cells is GLUT-4, which operates only at the bidding of insulin

Na⁺/K⁺ ATPase (pump) = Primary Active Transport 

         moving substances into or out of a cell requiring energy (ATP) 

          (carrier protein uses ATP) 

Pumps force molecules or ions to move from an area of low concentration to an area of high concentration

this is commonly referred to as “ against the concentration gradient ”

Sodium-Potassium Pump = Na+/K+ ATPase pump *

   (very important carrier protein) 

• Sodium-potassium pump is pumping sodium OUT of the cell and pumping potassium IN the cell

• this pump is the reason why its high concentration sodium outside the cell and 

high potassium inside the cell 

Remember this pattern… 

High sodium outside the cell — low sodium inside 

High potassium inside the cell — low potassium outside 

Steps of Sodium-Potassium Pump: 

• Pump picked up 3 sodium ions. ATP is attached to the pump, and when the 3 sodium ions bind, it activates the built in enzyme which CUTS ATP. the ADP floats away, and the phosphate stays attached to the pump. 

• The pump has been phosphorylated. This causes it to change shape and now it drops off the 3 sodium to the outside of the cell. 

• Pumped the 3 sodium ions from LOW to HIGH 

• Now it picks up 2 potassium from the low side, this causes the phosphate to fall off. The pump is dephosphorylated. This causes the pump to change shape and open to the inside of the cell where it drops off 2 potassium. It's now moved 2 potassium from low to high.

• The cycle repeats.

Review: 

• The pump is actively transporting 3 sodium ions outside of the cell, and 2 potassium ions inside of the cell. 

3 Na+ sodium OUT, 2 K+ potassium IN 

• Every single cell in the human body has sodium-potassium pumps, working NONSTOP. which is using a LOT of ATP. 

• Every single cell has leak channels for sodium and potassium, but the sodium-potassium pump is always pumping it back in. These are both happening at the same time. 

Absorption of Glucose in the Small Intestine

Luminal membrane vs. Basolateral membrane 

luminal membrane↓

↑basolateral membrane 

• Having these tight junctions there are also keeping the proteins in the luminal membrane on the luminal side, and keeping the proteins in the basolateral membrane on the basolateral side

The green structure in the luminal membrane is SGLT (sodium glucose transporter) brings sodium downhill so glucose can go uphill

The red circle in the basolateral membrane is the sodium potassium pump 

• Yes, SGLT brings in sodium, but the pump is pumping the sodium back out.

• The sodium potassium pump uses ATP, and that is working behind the scenes to maintain a sodium gradient. If the sodium potassium pump stopped working and no longer pumping sodium out of the cell, there would be too much sodium, no high to low balance, so glucose won’t be carried in anymore. 

• The point is to bring the glucose through the membrane 

Which kind of transport is the glucose transport system in the intestinal cell membrane? (The glucose is going from high to low) 

→ facilitated diffusion, GLUT 2

This one cell in the figure has all of these transport mechanisms to accomplish the absorption of glucose:

Osmosis is the mechanism for water to cross the membrane.

• Aquaporins are a type of channel protein

Membrane transport mechanisms 

1. Simple diffusion

2. Mediated transport 

3. Osmosis

• “diffusion of water”

• aquaporin (a type of channel protein)

• movement of water from an area of low concentration of solute particles to an area of high concentration of solute particles

• water follows solute — water goes from low solute to high solute 

When the membrane is permeable to BOTH water and solute … 

• The water goes from low to high, solute goes from high to low 

• Water concentration equal

• Solute concentration equal 

• No changes in volume of both sides 

When the membrane is NOT permeable to solute … 

• The solute cannot cross, but the water can.. so water moves from low solute to high solute 

• What changes is the water volume on two sides of the membrane

• Equilibrium means there is no more net movement 

• So, it reaches an equilibrium because of hydrostatic pressure

• The column of fluid got taller and taller on one side, which exerted hydrostatic pressure pushing back the other way. It reaches the point where osmosing (the water moving one way) was pushed back by the hydrostatic pressure (moving the other way) 

Hydrostatic pressure 

(the pressure exerted by a fluid due to gravity) 

• The steeper the gradient, the faster the diffusion. 

• Volume exerts more hydrostatic pressure, which pushes against the water trying to come across by osmosis 

• Osmosis is counterbalanced by hydrostatic pressure 

• It does reach equilibrium because there is no more net movement 

Osmotic Pressure ( 𝝅 )

• Osmotic pressure is the minimum pressure needed to prevent the flow of solvent molecules through a semipermeable membrane 

  • Osmotic pressure is how much do I have to push down to prevent the water from crossing, that means there more osmotic pressure 

• The bigger the concentration gradient, the harder you have to work to not have that water come across, so the bigger the osmotic pressure 

  • The bigger the solute gradient, the higher the osmotic pressure 

“Solute concentration” 

• depends on the number of dissolved particles (or the number of osmoles) in that solution 

• So… when you are thinking about water crossing the membrane, you talk about osmolarity 

Osmolarity = concentration of dissolved particles 

        = osm/L (osmoles per liter) = Osm (osmolar) 

        = mosm/L (milliosmoles per liter) = mOsm (milliosmolar) 

What is the difference between molarity and osmolarity?

• Osmolarity is different to Molarity because it measures OSMOLES OF SOLUTE PARTICLES rather than MOLES OF SOLUTE

• We make this distinction b/c some compounds can dissociate or separate in solution, whereas others cannot

For a solution, molarity and osmolarity may not be the same thing! 

1 M glucose = 1 Osm

(for glucose, its the same) 

1 NaCl = 2 Osm 

(for sodium chloride, it splits into two particles) 

1 M CaCl2 = 3 Osm 

(you get a calcium, a chlorine, and a chlorine) 

What is the normal osmolarity of a human cell? (You should have this number memorized!)

0.3 Osm is the “normal osmolarity” of the body 

 GIVEN: The following are the atomic masses of elements used in Questions #30-31:

                     C = 12            H = 1           O = 16                      

30. Calculate the osmolarity of a 2% glucose solution (C₆H₁₂O₆). (Answer: 0.11 OsM)

(in notebook)

31. What % solution is a 0.022 OsM glucose solution? (Answer: 0.4%)

  (in notebook)

Isosmotic = equal osmolarity to the cell 

Hypoosmotic = lower osmolarity than the cell

Hyperosmotic = higher osmolarity than the cell 

Lysis = cell swells  Crenate = shrinks

Nonpenetrating  = the solutes that cannot cross the membrane 

• Isotonic = the cell does not change size 

      cell stays the same 

• Hypotonic = lower osmolarity of nonpenetrating solutes than the cell does 

           water moves into the cell, which makes the cell grow larger

           cell swells/lyses 

• Hypertonic = higher osmolarity of nonpenetrating solutes than the cell does 

water leaves the cell

the cell shrinks/crenates in size

Tonicity means what happens to the cell when you put it in water.

Just because a solution is isosmotic, does not necessarily mean its isotonic

• In a solution of mixed solutes, only the concentration of nonpenetrating solutes contributes to the tonicity of the solution 

GIVEN: The following are the atomic masses of the elements used in Question #34:

                         Na = 23            Cl = 35             Mg = 24

34. Assuming the membrane is relatively impermeable to the following substances, what will happen to RBCs placed in these solutions? (HINT: need to think in terms of osmolarity!):

         a) 0.2 M MgCl₂   (Answer: it shrinks or crenates)

         b) 0.2% NaCl   (Answer: it swells and perhaps lyses)

Vesicular Transport 

(the movement of large molecules into or out of a cell within a vesicle)

1. Endocytosis (transport into the cell)

• the plasma membrane surrounds the substance to be ingested and then fuses over the surface, pinching off a membrane-enclosed vesicle so that the engulfed material is trapped within the cell

• in most instances, lysosomes fuse with the vesicle, degrading and releasing its contents into the ICF

2. Exocytosis (transport out of the cell)

• in exocytosis, almost the reverse of endocytosis occurs. A membrane-enclosed vesicle formed within the cell fuses with the plasma membrane, then opens up and releases its contents to the exterior

• provides a mechanism for secreting large polar molecules

Both processes of exocytosis and endocytosis are active – requiring energy.

3 forms of endocytosis, depending on the material internalized: 

1. pinocytosis (non selective uptake of a sample of ECF)

2. receptor-mediated endocytosis (selective uptake of a large molecule)

3. phagocytosis (selective uptake of a multimolecular particle)

Cholera:

• Diarrhea-inducing microorganisms such as Vibrio cholera, which causes cholera, are the leading cause of death in children younger than age 5 worldwide

• Cholera toxin prevents the involved G protein from converting GTP to GDP, thus keeping the G protein in its active state

Treatment for Cholera:

• Oral rehydration therapy (ORT)

the uncomplicated remedy that has been developed to combat potentially fatal diarrhea by exploiting the symporters located at the luminal border of the villus epithelial cells

Blood (Ch. 11) 

Your blood’s primary job is to transport things. 

Hematocrit (HCT)  = percentage of blood taken up by the red blood cells (RBC)

Plasma (ECF)

• mainly water 

with solutes (ions, amino acids, vitamins, glucose, hormones, etc.) 

with plasma proteins (most as made by the liver) : 

→ albumins 

(most common plasma protein)

(maintain the osmotic pressure of the blood) 

→ globulins ( ɑ , β , gamma ) 

→ fibrinogen 

Formed Elements of the Blood 

1. Platelets 

fragments of cytoplasm, not an actual cell

involved in blood clotting 

2. White blood cells (leukocytes) = WBC 

involved in defending against foreign invaders (a bacteria, virus, cancer cell, & more) 

3. Red blood cells (erythrocytes) = RBC

no nucleus

red because they are just a sack of hemoglobins 

→ Hemoglobin 

a protein 

4 polypeptide chains 

heme groups 

right in the middle of the heme group is an iron atom – Fe

primary job is to carry oxygen

→ Anemia 

the blood is not carrying enough oxygen

its a symptom, not a disease 

maybe they don’t have enough hemoglobin inside the red blood cells to carry oxygen 

→ Red blood cells (RBCs) 

only live 80-120 days (bc they don’t have a nucleus) 

1. Where do they go to “die”?

in the spleen and in the liver, the hemoglobins are broken apart 

the spleen gets rid of old RBCs  

bilirubin ends up in the liver, and put into a liquid called bile 

Bile: 

bile helps the body in the digestion of fats 

goes into the gallbladder, then into small intestine 

bile is colorful because it contains bilirubin

bile should only be in: the liver, gallbladder, bile duct, small intestine

→ Jaundice is a symptom where bile is in the blood

→ Gallstones are where bile has crystallized and may be blocking the bile duct, so the bile can’t get out 

Transferrin

(a plasma protein, made by the liver, for transporting iron) 

Ferritin

(mainly intracellular, to store excess iron; small amount in plasma)

a protein inside cells, especially liver cells, so that it can store iron 

The body is going to re-use the iron to make new RBCs. 

Red Blood Cells (RBCs) - only live 80 - 120 days 

1. Where do they go to “die”?

2. Where (and how) are new RBCs made? 

Hematopoiesis → process for making all the formed elements of the blood 

for adults, in the bone marrow (of certain bones)

Undifferentiated cell - not a specialized type of cell yet 

Stem cell - a cell that has retained its ability to divide

stem cells are in bone marrow

stem cells have multiple possibilities in what formed elements to become

b) Where (and how) are new RBCs made? 

→ Hematopoiesis 

→ Erythropoiesis 

(process to make RBCs; one part of the hematopoiesis picture)

erythropoiesis is a process where it loses the nucleus, which then becomes a red blood cell

partially regulated by erythropoietin (EPO)

Erythropoietin (EPO)

(a hormone produced by the kidneys during hypoxia) 

Hypoxia means there's low oxygen 

• if there's low oxygen in the blood, the kidneys are going to release this hormone called EPO into the blood 

• Erythropoietin travels to the bone marrow, which stimulates erythropoiesis 

• EPO operates under negative feedback 

Blood doping 

(doing various things to try to increase your oxygen carrying capacity of the blood)

• Athletes will take erythropoietin 

• They take EPO to increase red blood cell production, to have more oxygen, so the muscles can make more ATP – athletes can have more energy and endurance in these competitions 

What is the composition of Plasma (ECF)?

• mainly water 

with solutes (ions, amino acids, vitamins, glucose, hormones, etc.) 

with plasma proteins (most as made by the liver) : 

→ albumins 

(most common plasma protein)

(maintain the osmotic pressure of the blood) 

→ globulins ( ɑ , β , gamma ) 

→ fibrinogen 

Where are most plasma proteins made?

• Most are made by the liver

• The most common plasma protein are albumins 

Anemia

• the blood is not carrying enough oxygen

• its a symptom, not a disease 

• maybe they don’t have enough hemoglobin inside the red blood cells to carry oxygen

6 types of anemia

1. Nutritional anemia

2. Pernicious anemia 

3. Aplastic anemia

4. Renal anemia

5. Hemorrhagic anemia 

6. Hemolytic anemia

Sickle cell anemia

• caused by a genetic mutation that changes a single amino acid in the 146-long amino acid chain that makes up the β chain of hemoglobin

Malaria 

• caused by protozoan parasites introduced into a victim’s blood by the bite of a carrier mosquito

Polycythemia

• in contrast to anemia

• characterized by too many circulating RBCs and an elevated hematocrit

1. Primary polycythemia

• caused by a tumorlike condition of the bone marrow in which erythropoiesis proceeds at an excessive, uncontrolled rate instead of being subject to the normal erythropoietin regulatory mechanism

2. Secondary polycythemia

• an appropriate erythropoietin-induced adaptive mechanism to improve the blood’s O2-carrying capacity in response to a prolonged reduction in O2 delivery to the tissues

3. Relative polycythemia

• caused by the loss of body fluid, but not erythrocytes; the number of RBCs is not increased 

Signal Molecule

= ligand (this molecule is going to bind to a receptor)

= first messenger 

Signal transduction = where a signal molecule creates a response 

• This means, what are all the steps that has to happen between when a signal molecule shows up and actually having a response 

• This depends on your signal molecule

One classification system for signal molecules 

(classify based on where they act, as compared to where they came from)

→ autocrine 

• auto means self – it came from the cell and it acts on the same cell

• the signal molecule is acting on the cell that released it in the first place

→ paracrine 

• the signal molecule acts locally – on a neighboring cell in that tissue nearby

   (neurotransmitter) 

• neurotransmitters are paracrine, they act very locally on a neighboring cell 

→ endocrine = hormone 

• the signal molecule is released into the blood

• long-distance communication 

Alternate classification of signal molecules 

(classify based on their action) 

→ agonist 

• you’re getting the normal signal molecules response 

→ antagonist 

• something that will block the normal response – you are not getting the normal response 

• the doctor will prescribe an antagonist specifically because they want to block xyz

Another classification of signal molecules 

       (classify based on their chemistry) 

1. Lipid-soluble or hydrophobic 

• receptor is inside the cell (in nucleus or in cytoplasm)

2. Water-soluble or hydrophilic 

• receptor is in the cell membrane 

1. the receptor is an ion channel (specifically a ligand-gated channel)

2. receptor is a tyrosine kinase 

• Kinase = enzyme that phosphorylates molecules, such as proteins 

Review from Lecture 10: 

Membrane transport mechanisms

1. Simple diffusion (high to low, no energy needed) 

1. through phospholipid bilayer

2. through channel proteins 

1. leak channels (permanently open) 

2. gated channels (sometimes open, sometimes not) 

• there is something that is regulating whether the gate of the channel is open or closed 

• certain cells have gated channels 

• some gated channels are either: 

ligand-gated (chemically-gated) 

voltage-gated (electrically gated) 

mechanically gated (force or pressure) 

Exam Question: We have previously discussed phosphorylation. Which of the following membrane protein relies on phosphorylation? 

1. SGLT

• moving glucose uphill, its secondary active transport of glucose. The driving force for glucose going uphill is because sodium goes downhill, the glucose goes uphill. This has no phos

2. Na+/K+ pump

• active transport: moving sodium and potassium against their gradients

• it does this using ATP because the P stands for phosphorylation

3. GLUT

• glucose going downhill, no ATP

4. Na+ leak channel 

• sodium going downhill leaking through a pipe, no ATP

    Another classification of signal molecules 

(classify based on their chemistry) 

1. Lipid-soluble or hydrophobic 

2. Water-soluble or hydrophilic 

1. the receptor is an ion channel (specifically a ligand-gated channel)

2. receptor is a tyrosine kinase 

• Kinase = enzyme that phosphorylates molecules, such as proteins 

• Cascade = A phosphorylates B, then B phosphorylates C, then C phosphorylates D, etc. 

= amplifies the response!

How does the response end? 

• signal molecule goes away and 

phosphatases = dephosphorylate proteins and therefore deactivate them 

    Another classification of signal molecules 

(classify based on their chemistry) 

1. Lipid-soluble or hydrophobic 

2. Water-soluble or hydrophilic 

1. the receptor is an ion channel (specifically a ligand-gated channel)

2. receptor is a tyrosine kinase 

3. receptor is a G-Protein coupled

• there’s a G-protein attached to the receptor 

  • 3 subunits: alpha, beta, gamma 

• the alpha is attached to GDP

• the signal molecule attaches to the receptor, then activates the G protein, the GDP is released and replaced with GTP 

• now, G-Protein has been activated – now that its activated the alpha is going to separate from the beta & gamma 

• the alpha slides along the membrane & activates the effector protein

examples of effector proteins:

• an ion channel 

• adenylyl cyclase 

Next… 

• adenylyl cyclase (enzyme) converts ATP to cAMP 

Review:

• The first messenger is outside the cell 

• The second messenger is inside the cell 

cyclic AMP (cAMP)

  second messenger

• it activates protein kinase A 

  • cell-type specific 

• then phosphorylates proteins

• cascade reaction which amplifies the response!

How does the cAMP response end? 

1. signal molecule goes away 

2. cAMP phosphodiesterase 

• this is the enzyme to get rid of cAMP and changes it to plain AMP 

3. protein phosphatases 

• to get rid of all these activated proteins 

• removes the phosphates so the protein goes back to being inactive 

Distinguish first messenger from second messenger. 

Signal molecule = first messenger

The first messenger is outside the cell 

The second messenger is inside the cell 

First messengers directly bind to receptors on the cell membrane, while second messengers amplify and transmit the signal within the cell. 

• Ex of second messenger – cyclic AMP (cAMP)

  • cAMP has a cascade of reactions which amplifies the response

Many diseases can be linked to malfunctioning receptors or to defects in the ensuing signal transduction pathways. For example:

1. Laron dwarfism

• tissues cannot respond normally to growth hormone due to defective receptors

2. Chronic elevation of insulin

• leads to a reduction in the number of insulin receptors, thus reducing the responsiveness of this hormone’s target cells to its high levels

As another example, the toxins released by some infecting bacteria, such as those that cause cholera and whooping cough, keep second-messenger pathways “turned on” at a high level. For example:

1. Cholera

• prevents the involved G protein from converting GTP to GDP, thus keeping the G protein in its active state

2. Pertussis (whooping cough)

• blocks the inhibition of adenylyl cyclase, thereby keeping the ensuing second-messenger pathway continuously active

Ch. 3 : Electrical Properties of the Membrane 

Ions are crossing the membrane and that is what’s creating electrical properties of the membrane 

Ionic Equilibrium 

1. Scenario #1

• Permeable = can cross the membrane 

• Since K+ and Cl- goes does the concentration gradient, it reaches an equilibrium on both sides 

• The membrane is permeable (can cross the membrane) to K+, but A- (anionic protein) cannot cross 

• The concentration of K+ on side 1 is still higher than the concentration on side 2

• Anionic proteins have no change because the membrane was not permeable to A-

• However: K+ is at equilibrium because there's equal movement on both sides 

• This is Simple Diffusion

Review Question: What is the transport mechanism by which K+ would be crossing the membrane in this scenario? 

1. Simple diffusion 

• Ions move through simple diffusion, specifically through channel proteins. 

2. Facilitated diffusion 

• Facilitated diffusion is moving other solutes like glucose, things that are too big 

3. Primary active transport 

• these go from low to high 

4. Secondary active transport 

• these go from low to high 

5. More than one of the above 

Scenario #2 

• Even though the concentration of K+ is not equal on two sides of the membrane, the electric charge being equal on both sides 

electrochemical gradient

      is determined by 

chemical driving force + electrical driving force 

(concentration gradient) (the response to charge) 

Ions move because of the concentration gradient AND electrical properties. 

*** Because of differential permeability, there is a membrane potential, a separation / difference of charges across the membrane. 

(if charges are equal on both sides of the membrane, then the membrane has no potential) 

Membrane Potential 

• measured as voltage 

• common units: millivolts (mV)

• this measurement gives us an idea of how big the membrane potential is 

the more charges that are separated, the bigger the membrane potential 

(bigger number = higher voltage = higher membrane potential)

• How they measure membrane potential is using electrodes. They put one electrode ICF and one ECF

• Whatever your voltage is (negative or positive) , that's telling you the inside of the cell is negative or the inside of the cell is positive – the orientation of the charges

• Whether it's positive or negative, that's telling you what the inside of the membrane is. 

• sometimes it is a positive #

sometimes it is a negative #

-30mV vs. +20 mV

Q: which voltage is bigger?

A: -30mV is the bigger voltage 

(whether it is a negative or positive, it has nothing to do with the size of the voltage)

• because 30 is a bigger number than 20

Nernst Equation: 

• to calculate the membrane potential (mV) when an ion is at equilibrium 

• in other words, to calculate equilibrium potential

Nernst Equation: 

• Eion 

• 61 

• z = valence of the ion (what is the charge)

  • if you were going to run this calculation of z for sodium or potassium, you would plug in +1

• log

• Co = concentration outside ECF (TOP)

• Ci = concentration inside ICF (BOTTOM)

Calculation: 

• Plug in 61 divided by the valence (charge)

• Then multiply that answer by log (ECF on top / ICF on bottom) 

• Round answer and don't forget to include - or + 

Equilibrium potential:

• When the chemical driving force and electrical force cancel each other out, there’s no more net movement – so we are at equilibrium (positive #)

Exam Question: 

1. If sodium ions are always moving into the cell because of a chemical driving force, why doesn’t the concentration gradient change over time? 

• even though sodium is always leaking in, the Sodium-Potassium Pump is pumping it back out

2. Which ion do you think is more responsible for (in other words, contributes more to) getting the membrane to a resting membrane potential of -70 mV?

1. Na+

2. K+

• -70 mV is close to K+ equilibrium potential

      3.   How would we determine/know potassium’s equilibrium potential?

K+ contributes more to resting membrane potential b/c…

The membrane is MUCH MORE permeable to K+ than to Na+

1. The hydrated k+ ion is smaller than the hydrated Na+ ion

2. There are more leak channels for K+ than for Na+

Besides K+ contributing more to the resting membrane potential than Na+ … 

There are the Na+/K+ pumps!

1. Which is a bigger potential: -90 mV or +30 mV? 

• -90 mV

2. What is the distinction between -70 mV and +70 mV?

• Whatever your voltage is (negative or positive) , that's telling you the inside of the cell is negative or the inside of the cell is positive 

• Since -70 mV is the first one, it tells you that the membrane potential is negative on the inside ICF and positive on the outside ECF