Exam 2: Macromolecules: Proteins Flashcards
Functions of proteins (8)
- structure, hormones/signaling, neurotransmitters, blood clotting, viscosity, antibodies, transport, enzymes
What is the monomer of a protein and what is the chiral isomer?
amino acid
L-form
What does a monomer of a protein consist of
amino group, carboxyl group, R group (variation)
What type of rxns form peptide bonds?
dehydration rxns
Characteristics of peptide bonds (3)
- trans configuration
- planar
- rotation at bond
4 levels of protein structure
primary, secondary, tertiary, quaternary
Primary protein structure
amino acid sequence stabilized by peptide bonds
Secondary protein structure
alpha helix, beta pleated sheets
stabilized by interactions with primary carbonyl and amine groups forming domains
Tertiary protein structure
interaction between R groups
- covalent bonding, ionic interaction, hydrophobic interaction, hydrogen bonding
3D shape
Quaternary protein structure
interactions between peptide chains
same bonding types as tertiary
Chaperone proteins
first identified as heat shock proteins
- provide favorable environment for correct folding, prevents unfolding or unfolded proteins from forming aggregates, being degraded, or folding into toxic molecules
What diseases exhibit abnormal folding?
prion diseases
What are prions and what are some diseases they cause?
infectious proteins
cause: bovine spongiform encephalopathy, Creutzfeldt-Jakob, kuru, fatal familial insomnia
Where do prion proteins most commonly occur?
brain
What role do normal cellular PrPc prions have?
protective role
What PrPsc (scrapes)
abnormally folded proteins that form insoluble aggregates
What is the problem with protein aggregates?
they damage neurons and are resistant to degradation
PrPsc induce PrPc prions to convert…
increasing the number of dangerous prions
How did cows get mad cow (bovine)?
from calcium supplements (from bones of sheep) , sterilization can not kill off prions
Tissue Damage from prion diseases
holes in the brain, damaged brain tissue
motor function effected
prevents cell from functioning
What 2 diseases has research about prion diseases shed light on?
Alzheimer’s disease and Huntington’s Chorea
- all of these diseases involve neurotoxicity
- all have amyloid plaque formation
- misfolding exposes hydrophobic groups
Enzymes
- protein based
- highly specific for substrate
- catalyze all metabolic reactions by lowering the Ea
What type of reaction do you get when you have a negative change in free energy?
spontaneous reaction
How would a positive change in free energy make a rxn go forward?
if it was linked to a strongly negative reaction (hydrolysis of ATP)
Enzymatic factors that affect rates (4)
- with unlimited substrate, the enzyme concentration willl continue to rise
- reaction continues until all the enzyme is in the enzyme substrate complex, Vmax
- pH : affects charge and reactivity of active site
- T: rate increases until denaturation occurs
Holoenzyme
apoenzyme and a prosthetic group
apoenzymes
enzymes that need prosthetic groups in order to be functional
cofactors
inorganic
usually metal ions (Mg, Fe, Zn) that are required by certain enzymes
example of a cofactor
ATPases:
- require Mg2+ cofactor to put stress on the high energy bonds, it weakens the bond so it can be broken to get energy
coenzymes
organic
vitamins and carrier molecules
example of a coenzyme
pyruvate dehydrogenase:
- requires thiamine (B1) to act as electron sink for carboxylation of pyruvate
- alcoholics have issues with B1
Enzymes : Inhibitors
either prevent the binding of E to S or prevent the E from converting S to P
Competitive inhibitors
resemble S and bind to active site
Noncompetitive inhibitors
bind to allosteric site and alter the shape of or access to the active site
Inhibition can be…
reversible or irreversible
substrate level inhibition
occurs when an enzyme has 2 binding sites for the substrate (active and allosteric)
active site vs allosteric site
have diff Km and have diff affinities, bind at diff concentrations
binding at the allosteric site_____ at the active site
decreases the binding/conversion
What is substrate level inhibition useful for?
metabolic regulation and toxin mitigation
lower Km what affinity binds to it
higher affinity
higher km what affinity binds to it
low affinity
When you have a little bit of substrate…
it will go to the higher affinity, lower Km
When you have lots of substrate…
it will bind to the lower affinities since there is more of it and a higher Km
Application of substrate level inhibition: Phosphofructose Kinase
- if ATP increases, it will bind to the active site and the allosteric site making it harder to move forward
- do not put energy into it until there is a dec in ATP
What happens if you run out of ATP (substrate level inhibition)
the allosteric site does not pick it up and the rxn goes forward
- there is not enough to bind to the inhibitor site
What molecule level is being stabilized in substrate level inhibition of phosphofructose kinase?
ATP
- when more than enough ATP process slows to not waste energy
Application: Substrate Level Inhibition: Toxin Mitigation
What catalyzes the first step in the detoxification of alcohol?
alcohol dehydrogenase
acetate
nontoxic
alcohol
strong substrate level inhibition
acetaldehyde
highly toxic, vomiting, damage liver and heart, CNS
What happens when you get a build of acetaldehyde ?
you get nauseous quickly after drinking, skin flushes, enzymes not working well (Sami)
What happens when the conversion to the intermediate is slowed down?
most negative effects can be somewhat mitigated
increase in alcohol, it binds to the _____…..
allosteric site slowing it down to mitigate dangerous effects of intermediate , minimizes toxicity
product level inhibition
product binds to an allosteric site on the enzyme to slow the reaction
- involved in metabolic regulation
Example of product level inhibition
hexokinase and Kreb’s cycle enzymes
inhibition ensures glucose will not be dedicated to ATP production unless the cell is utilizing it
Km
affinity of E for S
lower the Km, higher the affinity
[S] at 1/2 Vmax
Vmax
capacity of E to handle fluctuations in S
when all E is in the ES complex
isoenzymes
catalyze the same reaction but have different activity levels due to minor structural changes
Isoenzymes are ____ specific
tissue specific
hexokinase vs glucokinase
glucokinase is a type of hexokinase
hexokinase: found in most tissues (brain, muscle) and is the “maintenance” enzyme - hard to upregulate
glucokinase: found primarily in the liver upregulated more than hexokinase
Application isoenzymes: what can G-6-P be directed to
glycolysis and cellular respiration
under conditions of high ATP and low ADP, Kreb’s cycle enzymes will ______
not move the process forward
Build up of citrate will stimulate…
biosynthesis of fatty acids
What would happen to the liver in a consistently high sugar environment?
- build up of fat in liver
- liver can make G6P, no inhibition , pushing glycolysis get to Krebs, it says no and you can make fat and glycogen
liver trying to process extra sugar
What does an increase in an isoenzyme in the bloodstream indicate?
you have had tissue damage
- dying cells released into bloodstream
CPK1
brain, lungs
CPK2
heart
CPK3
skeletal muscle
