Lipid bilayer, separates cell contents from exterior, controls movement in and out of cell
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Cytoplasm
Highly organized network inside cell, liquid portion called cytosol, many biochemical processes occur here
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Nucleus
Information center of cell, DNA & RNA synthesis (transcription)
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Mitochondria
Produces 90% of energy for cell, has 2 membranes, has some genetic info here.
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Endoplasmic Reticulum
2 Parts:
Smooth ER - Produces lipids -- think smooth like butter
Rough ER - Studded with ribosomes that make protein
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Golgi Complex
Makes proteins from RER more specific and sorts them
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Secretory Granule
Vesicle budded off from golgi complex, waits for extracellular signal to fuse with plasma membrane and release contents
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Endosome
Vesicle formed from contents taken in by cell (endocytosis)
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Lysosome
Contains digestive enzymes
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Peroxisome
Contains oxidative enzymes used to protect cell
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Which cell organelle is responsible for synthesizing lipids?
Smooth ER
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Which organelle is the digestive system of the cell?
Lysosome
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What are the 2 ways to evaluate cells?
In vitro - Experiments performed in glass
*helps determine cellular mechanisms, doesn’t tell the whole story*
\ In vivo - Experiments done in whole, living organisms
*Difficult to control all variables*
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99% of mass of cell is made of what?
Hydrogen, oxygen, nitrogen, and carbon.
\ *the lightest elements form the strongest bonds*
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What are the 4 universal classes of biomolecules?
Proteins → Made of amino acids, signaling molecules, receptors, enzymes, structure, immunity.
\ Nucleic Acids → Information keepers of the cell; deoxyribonucleic acid (DNA) & ribonucleic acid (RNA)
\ Lipids → Important for membranes; energy storage
\ Carbohydrates → Made of sugar, important source of energy; cell recognition.
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What is a functional group?
A compound’s structure and function (aka personality) is determined by the functional groups it contains.
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What are the 4 types of hydrocarbons?
Alkanes - only has single bonds
\ Alkenes - has a double bonded carbon
\ Alkynes - has a tripple bonded carbon
\ Aromatics - contains 6 carbons with alternating single and double bonds in circle.
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Alcohol
Contains a hydroxyl group (OH)
\ ex. Ethanol
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Aldehyde
Contains a carbonyl on the *end* of the molecule
\ O=C-H
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Ketone
Contains a carbonyl in the *middle* of the molecule
\ C=O
\ Ex. Propan__one__ or acet__one__
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Carboxylic Acid
Contains a carbonyl and hydroxyl at the *end* of the molecule
\ O=C-OH
\ Carboneal & Alcohol
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Pentanoic Acid
COOH
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What do you do when acids are ionized?
Replace “-ic acid” with “ate”
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Ester
Acid + Alcohol
\ Carbonyl and oxygen in the *middle* of the molecule
\ O-C=O
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What does it mean to be esterified?
Contains an ester bond
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Ether
Reaction of 2 alcohols
\ Oxygen connecting 2 carbon chains
\ R-O-R
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What is Organic vs Inorganic
Organic → Contains hydrocarbon (C & H)
\ Inorganic → Does NOT contain hydrocarbon
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Why is configuration and conformation important?
The 3D structure is determined by a molecule’s configuration and conformation
\ The 3D structure determines how it will interact or “fit” with other biomolecules
\ Configuration is the spatial arrangement of atoms based on presence of double bonds or chiral centers
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Stereochemistry - Chirality
If they are not superimposable, they have a chiral center - Carbon with 4 different groups bonded to it.
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Isomer Types
Structural Isomers → Same formula, different order of attachment
\ Stereoisomers → Same formula & order of attachment, different 3D arrangement
\
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What are the two types of Stereoisomers?
Entantiomers → Nonsuperimposable mirror images
\ Diastereomers → NOT mirror images
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What are the two types of Diastereomers?
Geometric Isomers → Different rotation around a double bond
\ Epimers → Different rotation around 1 carbon (C1)
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Oxidation & Reduction
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Where are oxidation reactions found in?
Metabolism
\ Formation of heart disease (LDL oxidation)
\ Cancer (oxidation of DNA can initiate cancer)
\ Aging (oxidation can damage tissues and cause wrinkles)
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Reduction Example
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Dehydration
Removal of water → Water is a product!
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Hydration
Addition of water across a double bond.
\ Water is a reactant!
\ Double bond is broken by water to form a single bond. Product is a secondary alcohol
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Hydrolysis
Water is used to break a single bond.
\ Water is a reactant!
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Digestion of all macronutrients occurs via what?
Hydrolysis
\ Carbs, lipids, and proteins must all be digested prior to absorption.
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What is the formation of soap from vegetable oil called?
Saponification
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What is Methylation?
Addition of a methyl group
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Phosphorylation
Addition of a phosphate group
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Phosphorylation
ATP to ADP
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What is equilibrium?
Reaction where the forward and reverse reaction are occurring at the same rate resulting in no net change in amounts of reactants & products
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What is steady state?
Rate of intake or synthesis occurs at the same rate that it is being used up
\ maintaining steady state (constant blood glucose or oxygen concentration) requires constant investment in energy.
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What is the first law of thermodynamics?
Energy is neither created nor destroyed → Energy is transferred within the system.
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Endergonic Vs Exergonic
Endergonic = Requires energy
Delta G = positive
\ Exergonic = Energy releasing
Delta G = negative
\ *for a reaction to spontaneously occur, we want the sum of delta G to be negative*
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What is Energy Coupling?
When two molecules are combined and their combined charges equate a charge. If that combined charge is negative, then the reaction will happen spontaneously (exergonic).
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Catabolic vs Anabolic Pathways
Enzymes speed up chemical reactions.
\ Catabolic = Breakers
Anabolic = Builders
\ Catabolic + anabolic = metabolic
*Metabolic enzymes are highly regulated*
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What is the 3 legged stool of Evidence-Based Clinical Practice (EBCP)
Clinical Expertise + Patient Values + Current Best Evidence
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How do you appraise clinical trials?
See image
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Measurement of Risk
Absolute Risk (AR) → True incidence of disease, also called risk difference
Subtraction - (control/100) minus (trial/100)
ex. 40/100 - 30/100 = .10 = 10%
\ Relative Risk (RR) → Aka risk ratio, measure of probability of risk. Only used in cohort studies.
Division - (trial/100) divided by (control/100)
ex. 30/100 / 40/100 - .75 = 1-.75 = .25 = 25%
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Interpreting RR
If RR = 1
No association, risk in exposed = risk in non-exposed
\ If RR>1
Positive association (increased risk), risk in exposed > risk in non-exposed
\ If RR
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Interpreting OR
If OR = 1
No association, exposure is not related to disease
\ If OR >1
Exposure is positively related to disease, positive association (increased risk)
\ If OR
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How to tell if a result is significant?
What to look for?
Confidence Interval (CI) → 95% CI says that I’m 95% sure that the actual result falls in the calculated range.
\ If the CI crosses the referent number, it is not significant. It can touch or come near line, but cannot cross it. If it crosses 1, it is not significant.
\ ex. (1.02-1.65) = significant
(.99 - 1.25) = NOT significant
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What is Number Needed to Treat (NNT)?
How many patients need to receive the treatment for one patient to benefit. You want a small NNT.
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Correlation vs Causation
Correlation
Can find an association.
NOT cause & effect
Closer correlation coefficient is to 1, the greater the association
Results from cohort studies
\ Causation
Can tell true cause and effect
Only determined by randomized control trials
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Water
The most abundant substance in living systems
\ Human body is \~65% water by weight, typical call is 70% water
\ Electronegativity can also help determine which element is more polar and less polar - called dipoles
\ Biomolecules are held together by strong (covalent) interactions
\ *Water’s ability to form weak (non-covalent) interactions is extremely important to function*
Although weak, there is stability in numbers.
Transient weak changes allow for dynamic interactions.
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Types of Interactions
Covalent and Noncovalent
Covalent → True Bonds; determined by electronegativity difference
Noncovalent → Not true bonds, but intermolecular forces (IMF)
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Hydrogen Bonds
*Not true bonds, attractive forces between compounds*
\ Between H and O or N
\ Important in the double helical structure of DNA and 3D folding of proteins
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Electrostatic Interactions
Forces between ions (cations and anions)
\ Can be attractive or repulsive
\ Charged molecules dissolve readily in water
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Hydrophobic Interactions
Between nonpolar compounds
\ Hydrophobic molecules cluster together in a polar solution
\ Called “Hydrophobic effect”
\ Not because they like each other
Due to highly ordered structure of water surrounding nonpolar clusters
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What drives the formation of the lipid bilayer in membranes?
Hydrophobic Interactions
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What drives the folding of proteins as they associate in the interior of the protein?
Nonpolar amino acids in protein.
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Van der Walls Interactions
Aka London Dispersion Forces (LDF)
\ Weakest of all the attractive forces
\ Interaction between 2 uncharged compounds in close proximity
\ Found in all polar and nonpolar compounds
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Passive (simple) Diffusion
Molecules move from high to low concentration gradient
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Osmosis
Diffusion of water molecules from a higher to lower water concentration
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Facilitated diffusion
Moves from high to low concentration gradient with help of transport protein
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Hypotonic
Solution with a lower solute concentration
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Hypertonic
Solution with a higher solute concentration
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Isotonic
Equal solute concentrations
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How do cells remain isotonic?
Large amounts of albumins and other proteins in blood
\ Cells being able to actively pump Na+ and other ions out of cells
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Cell Permeability
See image
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How are weak acids measured?
By the acid dissociate constant (Ka)
\ Stronger acids have a bigger Ka (more likely to dissociate)
Weaker acids have smaller Ka (less likely to dissociate)
\ pKaa = -logKa
When pH = pKa, there is equal amounts of a weak acid and its conjugate base.
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pKaa General Rules
pKaa is a lab determined number that is relatively constant
\ pH will change substantially throughout body fluids
\ If pH is below pKaa = H is still attached.
\ If pH is at pKa = half attached, half lost.
\ If pH is above pKaa = H is lost.
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Biochemical Acids
Acids are substances that can donate H+ to lover the pH
\ Volitile acids - can be turned into a gas & eliminated through lungs
*most important is carbonic acid*
\ Nonvolatile acids - cannot be turned into gas, must be eliminated through kidneys
*end products of carb, protein, and lipid metabolism*
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Biochemical Bases
Bases are substances that can accept a H+ to increase the pH
\ Most important base in vivo = bicarbonate (HCO3-)
Primarily regulated by the kidneys
\ Fruits and vegetables are also basic in nature when metaboliced.
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pH Imbalances
Acidosis
Accumulation of acid or loss of base
\ Alkalosis
Accumulation of base or los of acid
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Buffers
Usually a weak acid and its conjugate base
\ A buffer is anything that can reversibly bind protons (H+)
\ Chemical solution designed to resist a change in pH despite addition of acids or bases
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What is the buffer for extracellular fluid?
Bicarbonate-carbonic acid buffer system
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What is the buffer for intracellular functions?
Protein buffer system (ex. hemoglobin in RBC), phosphate buffer
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What is the buffer for kidneys
Phosphate buffer system and bicarbonate-carbonic acid buffer system
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Chemical buffers in body fluids
Bicarbonate/carbonic acid system, phosphate buffering and proteins
\ Takes seconds to minutes
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Respiratory Buffers
Regulate CO2 concentrations
\ Takes minutes
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Kidney buffering systems
Excrete acidic or basic urine
\ Takes hours to days
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T/F - Acid production increases the free H+ pool, thus decreasing the pH
True
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T/F - Base production pulls free H+ from the pool, thus increasing the pH
True
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Proteins are amphoteric, what does that mean?
They can act as an acid or a base
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Phosphate Buffers
Intracellular
\ Found inside all cells
Resits changes in pH between 5.9 and 7.9
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How do you buffer an excessive acid?
Base and protein
\ Carboxylate and protein
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How do you buffer and excessive base?
Acid and protein
\ Amine and protein
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Bicarbonate buffering system
Respiratory & renal pH regulation
\ Respiratory buffers → control concentrations of carbon dioxide
Renal buffers → control concentration of H+ or bicarbonate
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Respiratory Control of Bicarbonate Buffer System
Lungs and brain stem control CO2 concentrations by dictating breathing rate = Respiratory buffers
\ Increase in CO2 signals the brain to increase breathing rate
Decrease in CO2 signals the brain to decrease breathing rate
\ Too much CO2 = Respiratory Acidosis
Too little CO2 = Respiratory Alkalosis
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Metabolic Acidosis
Caused by any other mechanism other than increased CO2
\ Usually due to loss of bicarbonate or excessive nonvolatile acids
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