Control of Enzyme Activity—Introduction to Metabolism Flashcards
What is metabolism ?
highly integrated network of chemical reactions
catabolism
catabolism : fuel to energy
anabolism
anabolism: energy + simple precursor to complex molecule
Ways of Regulating Metabolic Processes (Pathways)?
contolling amount of enzymes,catalytic activity and compartmentalization of substrates
5 Ways of Controlling Enzyme Activity
Amount of enzyme in the cell Allosteric control of enzymes Through existence of ISOZYMES Reversible covalent modification Proteolytic activation
allosteric enzymes? (4 things it does)
exhibit cooperativity in responses to substrate
obey the Monod-Wyman-Changeux (MWC) model
Often serve as control points in pathways
Subject to feedback inhibition
Monod-Wyman-Changeux (MWC) model of allosteric behavior
Equilibrium between “T” and “R” states exists; allosteric effectors shift equilibrium
what Catalyzes first committed step of pyrimidine synthesis (in E. coli):
ATCase
in the 1st committed step of pyrimidine synthesis, what compound controls allosteric inhibition and activation? (2 separate things)
CTP inhibit
ATP activate
two subunits seen in Aspartate Transcarbamoylase, ATCase
C (catalytic site)and
R (regulatory site)
Which site does ATP and CTP bind too
R site
what is a Competitive inhibitor of both substrates, aspartate and carbamoyl phosphate?
PALA -N-(Phosphonacetyl)–L-Aspartate
Upon binding PALA will place ATCase in the __ state ?
R
in absence of substrate aspartate, ATCase will exist in what kind of state ?
Low activity T state
in the presence of CTP ATCase will exist in what kind of state ?
Low activity T state
Higher levels of aspartate increasingly shift equilibrium from
T” to “R”
Inhibitor CTP shifts equilibrium toward __ state ?
T
Activator ATP shifts equilibrium toward __ state?
R
Why ATP would activate ATCase?
why is ATP used in this reaction
Pyrimidine-purine balance needed for mRNA or DNA synthesis
Isozymes are Homologous enzymes that catalyze same reaction BUT
Are encoded by different genes
Hve similar AAs
Are often expressed in a tissue-specific or developmental stage-specific manner
An example of an isozyme is ?
LDH
Combitations of teramers possible by LDH
M4, M3H, M2H2, MH3, H4
6 Different Post-Translational Covalent Modification of Enzymes/ Proteins?
phosphorylation, acetylation, carboxylation, ubiquitylation, lipidation, glycosylation
in phosphorylation what catalyzes the attachment and removal of phosphate?
protein kinase
removal- protein phosphatase
In phosphorylatipn what different residues do phosphates attach too ?
serine, threonine, or tyrosine
Acetylation activates __?
gene transcription / opens up DNA
Ubiquitylation In cytoplasm targets proteins for destruction via the
proteaosome
In the nucleus this type of modificationcan alter properties of histones and other proteins involved in gene expression
ubiquitylation
which covalent Modification allows the clotting factors to chelate calcium and adhere to vessel wall near site of injury ?
carboxylation
Allows the subunits to move along the cytoplasmic face of membrane; speeds up their interaction with downstream effectors
lipidation
Gs(alpha) with adenylyl cyclase is seen in this type of covalent modification
lipidation
Attachment of carbohydrate groups, including modified sugars (GlcNAc) and oligosaccharide groups is seen in this type of covalent modification ?
glycosylation
Which residues (AA) does glycosylation attach to ?
Covalent attachment is to serine, threonine or asparagine residues
in glycosylation, modification is directed to (3 things ) ?
Modification is to extracellular domain of transmembrane proteins, or secreted proteins (e.g., EPO), or proteins destined for lysosome
chelate ?
compound containing a ligand bonded to a central metal atom at 2 more points? “grab and bond to “
phosphorylation and glycosyation are the only reversible reactions in Post-Translational Covalent Modification of Enzymes/ Proteins?
Falce : phosphoylation AND aceylation
ATP provides energy by simple hydrolysis. T/F?
False. ATP provides energy by group transfer.
what is used to lower ADP levels during periods of intense demand for ATP
Adenylate kinase
reasons why there is a large (-) delta G of hydrolysis of ATP?
- More resonance forms
- less bond strain (repulsion) in ADP
- Greater degree of solvation (hydration) in products
Coupled reactions
refers to coupling unfavorable and favorable reactions to drive reaction forward
coupled reaction examples
- Unactivated vs activated conformations of a motor protein
- hydrolysis of ATP
- ATPase
what compound has 2 phosphoanhydride bonds that, when hydrolyzed, yield a lot of free energy
ATP
Phoshpoanhydride bond?
links a ribose sugar and. three phosphate groups
High energy compound thar rapidly synthesizes ATP when low in the muscle
creatine phosphate
In exercise __ ttansfers phosphryl group to ADP to generate ATP
Creatine phosphate
In enol phosphates such as phosphoenolpyruvate what will give the product more stabiulty than reactant
the ability to tautomerize
tautomerism
isomers of a compound which differ only in the position of the protons and electrons. usually seen as a PROTON TRANSFER
ATP generating pathways are __ by high energy charge
inhibited : seen in catabolic
ATP utilizing pathways are __ by high energy charge
activated :seen in anabolic
activated carriers of electrons for fuel oxidation
NAD+, NADH and FAD
activated carriers of elctons for reductive biosynthesis
NADP+, NADPH .
[NADP+]/[NADPH] is kept low or high ?
low so hydride trasfer favors [NADPH]
[NAD+]/[NADH] is kept low or high ?
HIGH low so hydride trasfer favors [NAD+]
this type of covalent modification is seen in the alpha and beta/gamma subunits of heterotrimeric G-proteins
lipidation
