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Lectures 2-4
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What is homeostasis?
a condition of equilibrium/balance in the body’s internal environment that is maintained by the body’s regulatory processes
To maintain homeostasis, a control system must be able to:
1) _________________ in the internal environment that need to be held within narrow limits
2) _________________ with other relevant information
3) _________________ to restore a factor to its desired value
detect deviations from normal, integrate this information, make appropriate adjustments
What is the set point?
the normal range for a given system
What monitors the set point?
the control center for that particular system
_______________ is a major regulatory factor for nearly all physiological activities and its disorder can have severe consequences on human health
the circadian rhythm
What are the 2 classes of homeostatic control systems?
1) intrinsic controls → local controls that are inherent to an organ
2) extrinsic controls → regulatory mechanisms initiated outside an organ, accomplished by the nervous + endocrine systems
What are feedback loops?
responses made after a change (negative or positive feedback loop)
What are feedforward loops?
responses made in anticipation of a change
What are the basic components of a feedback loop?
stimulus → sensor → control center → effector → response
What is a negative feedback loop?
primary type of homeostatic control that opposes the initial change
What are the components of a negative feedback loop + what does each component do?
sensor → monitors magnitude of a controlled variable
control center → compares sensor’s input with a set point
effector → makes a response to produce a desired effect
The main goal of a negative feedback loop is to keep the internal environment stable. What are some examples of what a negative feedback loop might control?
body temperature
nutrients/wastes
O2/CO2 levels
pH
water/electrolytes
blood volume
blood pressure
What is a positive feedback loop?
feedback loop that amplifies an initial change (response reinforces the stimulus) + therefore does not truly contribute to homeostasis
What is the difference between disorder + disease?
disorder → general term for any abnormality of function
disease → more specific term for an illness characterized by a recognizable set of signs + symptoms
___________ is a normal process characterized by a progressive decline in the body’s ability to restore homeostasis.
Aging
What is an example of a feedforward mechanism?
saliva production prior to eating (mechanism to prepare for breakdown of carbohydrates)
Feedforward regulation occurs through _________________, priming the body for the changes that are about to take place.
central command
Energy balance can be represented by what equation?
Energy intake = internal heat produced + external work + internal work + energy storage
Why is there a balance between energy input + energy output?
the law of thermodynamics → energy cannot be created or destroyed
What is energy input?
energy from ingested food → cells capture portion in high energy bonds of ATP, which allows us to have energy output
What are the components of energy output?
external work
energy expended when skeletal muscles are contracted to move external objects or to move the body in relation to the environment (only about 25%)
energy from nutrients that is not used to perform work
transformed into thermal energy/heat (about 75% of energy)
What is internal work?
all other forms of biological energy expenditure that do not accomplish mechanical work outside the body:
skeletal muscle activity used for purposes other than external work (postural contractions, shivering)
continuous activities to sustain life
What are the 3 possible states of energy balance?
1) neutral energy balance → energy input = energy output (bodyweight remains constant)
2) positive energy balance → energy input > energy output (bodyweight increases, excess energy stored as adipose)
3) negative energy balance → energy input < energy output (bodyweight decreases, body uses stored energy to supply energy needs)
What is metabolic rate?
total amount of energy we need to expend (both internal + external) to perform a given task
What is basal metabolic rate (BMR)?
the minimal energy expenditure we need to maintain in order to meet the basic physiological functions in our body
What are the factors that influence metabolic rate?
thyroid hormone levels (primary determinant of BMR)
sympathetic stimulation: epinephrine/norepinephrine
exercise (muscles burn more calories at rest)
daily activities
sex/gender
age
What is metabolism?
the set of life-sustaining chemical processes that enables organisms to transform the chemical energy stored in molecules (carbs, lipids, proteins) into energy that can be used for cellular processes
What is the difference between anabolic and catabolic?
anabolic: building of molecules
catabolic: breaking down of molecules
How do enzymes act as catalysts for chemical reactions?
they lower the activation energy
Since each enzyme is only able to control a single type of chemical reaction, if an enzyme is not active, what happens?
the entire pathway will stop working
What is competitive inhibition?
an inhibitor molecule binds to the enzyme’s active site + prevents the substrate from binding
What is non-competitive inhibition?
an inhibitor molecule binds to the enzyme at a different site than the active site (allosteric site) and changes the shape of the enzyme so it is no longer in optimal position to catalyze the reaction (substrate can still bind to the active site)
What happens to the reaction rate when substrate concentration is increased in the presence of a competitive inhibitor?
The reaction rate increases, eventually reaching the same maximum velocity (Vmax) as an uninhibited reaction, but requiring a higher substrate concentration to do so. This is because the substrate molecules outcompete the inhibitor for the active site on the enzyme, and at a high enough substrate concentration, the substrate effectively displaces the inhibitor, allowing the enzyme to function at its maximum capacity
What happens to the reaction rate when substrate concentration is increased in the presence of a non-competitive inhibitor?
Increasing substrate concentration does not increase the reaction rate to the normal maximum. This is because the number of active enzyme molecules is reduced by binding to a site distinct from the active site, effectively "poisoning" a portion of the enzyme regardless of substrate availability. Consequently, the reaction's maximum velocity is permanently lowered
What is an allosteric activator?
molecules that can bind to an allosteric site on an enzyme which causes a conformational change that increases the affinity of the enzyme’s active site for its substrate, thus increasing the reaction rate
Many enzymes only work if bound to non-protein helper molecules called __________ and __________.
cofactors, coenzymes
What is the main function of cofactors + coenzymes?
on/off switch, binding to these molecules promotes optimal conformation + function for their respective enzymes
What are the most common coenzymes?
dietary vitamins
What is feedback inhibition?
when a reaction product is used to regulate its own further production (product stimulates or inhibits further activity)
Of the 4 major macromolecular groups (carbs, lipids, proteins, nucleic acids), which is most common source of energy to fuel the body?
carbs
_________________ are one category of reactions important in energy transfer. Where in these reactions is energy captured?
oxidation-reduction (redox) reactions, energy is captured from the energy released during oxidation reactions when ATP is formed
What are the 3 main phases to cellular respiration?
1) glycolysis
2) Kreb’s cycle (TCA cycle)
3) electron transport chain (ETC)
What process of cellular respiration is the quickest way to get energy?
glycolysis
Glycolysis is the breakdown of glucose into ____________
pyruvate
In the liver, hepatocytes either pass the glucose on through the circulatory system or store excess glucose as ______________.
glycogen
What is glycogenolysis?
the breakdown of glycogen into glucose
Where does glycolysis mainly occur?
in the cytosol of the cell
Through the process of glycolysis, how many ATP molecules and NAD+ molecules are used to convert one glucose molecule? What are the products?
2 ATP and 2 NAD+ are used to convert 1 glucose into 2 pyruvate, 4 ATP (net 2) and 2 NADH
What step of glycolysis is the first committed step? What enzyme catalyzes this step?
the 3rd step, phosphofructokinase
What are up-regulation + down-regulation?
up-regulation is when cellular components such as receptors or genes increase to enhance a cell’s response/sensitivity
down-regulation is when cellular components such as receptors or genes decrease to reduce a cell’s response/sensitivity
What causes up-regulation in glycolysis?
high levels of AMP mean that the cell is low in energy (ATP), so this stimulates phosphofructokinase (PFK) so glycolysis continues (makes more ATP)
What causes down-regulation in glycolysis?
high levels of ATP (ATP is a negative regulator or PFK) lets cell know that glycolysis doesn’t need to continue
citrate build-up (first product of the citric acid cycle) is a sign for glycolysis to slow down b/c citric acid cycle is backed up + doesn’t need more fuel
Why are mature mammalian red blood cells not capable of aerobic respiration? What is their sole source of ATP?
they do not contain mitochondria, so glycolysis is their only source of ATP
What happens to red blood cells if glycolysis is interrupted?
the cells lose their ability to maintain their Na+/K+ pumps, so eventually they die
When does the Kreb’s/TCA cycle take place?
if oxygen is available
What happens to the pyruvate molecules produced by glycolysis?
transported into the matrix of the mitochondria (site of oxidative cellular respiration) + transformed into acetyl CoA
The TCA cycle is a closed-loop series of __________ and ___________ reactions that remove ___________ and ____________.
redox, decarboxylation, high-energy electrons, CO2
Why does the Kreb’s cycle occur twice for 1 glucose molecule?
b/c 2 pyruvate molecules are produced from 1 glucose molecule
How many NADH and FADH2 molecules are produced from each round of the TCA cycle?
3 NADH, 1 FADH2
What is the yield from 1 glucose molecule that has gone through glycolysis + the TCA cycle?
2 ATP + 2 NADH from glycolysis
2 NADH come from conversion of 2 pyruvate into 2 acetyl CoA molecules
each round of the Kreb’s cycle:
1 ATP
3 NADH
1 FADH2
CO2
all x2 b/c of 2 pyruvate
TOTAL YIELD:
4 ATP
10 NADH
2 FADH2
CO2
Where does most of the ATP generated during aerobic metabolism of glucose come from?
the electron transport chain
The electron transport (ETC) is the only part of the glucose metabolism that uses ____________.
atmospheric oxygen
The ETC functions as a series of _____________ that enables electrons to be passed from one component to the next. The protons expelled into the intermembrane space from the ETC are used to form ATP through ____________.
4 redox reactions, chemiosmosis
What happens during chemiosmosis in the ETC?
protons diffuse down the gradient through ATP synthase, which harnesses this energy from the flow of the protons to catalyze the pairing of a Pi with ADP, to form ATP
How much ATP comes from NADH and FADH2?
NADH → 3
FADH2 → 2
What is the total net ATP from one glucose molecule by the end of aerobic respiration? Where does it come from? Is all of it used?
Total: 4 ATP, 10 NADH, 2 FADH2
Total net ATP: 4 ATP, 30 ATP (from 10 NADH), 4 ATP (from 2 FADH2)
TOTAL: 38 ATP
never use all of it, only ~30-32 ATP is used
What is fermentation?
metabolism without oxygen
When oxygen is not present, NADH produced through glycolysis must be ________________ to ________ for reuse as an electron carrier for the _________________ to continue.
re-oxidized, NAD+, glycolytic pathway
What is the fermentation method used by humans? When and where is this type of fermentation used?
lactic acid fermentation
used in red blood cells + skeletal muscle that has an insufficient oxygen supply to allow aerobic respiration to continue
In muscles, lactate accumulation through fermentation must be removed via the _________________, which brings the lactate to the ____________, where it is further metabolized.
circulatory system, liver
What occurs during fermentation?
pyruvate molecules are converted to lactate, this process creates NAD+ from NADH
What is the function of the NAD+ produced from converting pyruvate to lactate?
NAD+ can now be recycled to allow glycolysis to continue
To obtain energy from fat, triglycerides must be broken down by _____________ into their two principal components: ____________ and ____________
hydrolysis, fatty acids, glycerol
How are the fatty acids from fats converted into acetyl CoA?
fatty acids are oxidized by beta-oxidation, which is used by the Kreb’s cycle
Is beta-oxidation fast or slow?
slow
What is the body’s last choice for energy production?
protein
How can protein be used as a fuel source?
can be broken down into amino acids which can enter cellular respiration at the pyruvate/acetyl CoA or TCA cycle stages