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Metabolism

Terms in this set (118)

principles of metabolic pathways
irreversible, first committed step, regulated, occurs in specific cellular locations
enzymes that control rate limiting steps are regulated by:
allosteric modulators, covalent modification, substrate concentration, enzyme concentration
gibbs free energy at equilibrium
Zero
coupling of reactions
by coupling an energetically unfavorable reaction with one that gives off extra energy
energy charge has to do with:
ratios between ATP, ADP and AMP in the cell
High energy charge = 1.0
ATP
Low energy charge = 0
AMP
High energy charge favors
anabolic reactions
low energy charge favors
catabolic reactions
hydrolysis of ATP
Releases energy
ATP synthesis
oxidative phosphorilation, glycolysis, citric acid cycle
enzyme complexes of respiratory chain
4 enzyme complexes: I) NADH-Q reductase, II) succinate-Q reductase, III) cytochrome reductase, IV) Cytochrome oxidase
mobile carries of respiratory chain
Q (ubiquinone), citochrome c
enzyme complexes that pump protons
I, III, IV
electron carriers in oxidative phosphorilation
NADH, FADH2
final electron acceptor
O2
electrons moving along electron transport chain
each complex is reduced as they accept an electron and oxidized as it passes electrons to the next complex
proteins that channel electrons into the electron transport chain
succinate dehydrogenase, glycerol 3-phosphate dehydrogenase
oxidative phosphorylation is controlled by:
availability of substrates: NADH, O2, ADP, and phosphate
blocked NADH-Q reductase by amytal rotenone
Oxidative phosphorylation can still take place, because electrons can be fed into ubiquinone
antimycin A blocks complex III
oxidative phosphorylation will be shut down because there is no other complex to accept electrons
ATP synthase
Head place for ATP synthesis, pore proton channel
Synthesis of ATP
as protons go through pore, catalytic sites change conformation, need 3 protons for each ATP formed
Yield of ATP in oxidative phosphorylation
NADH = 2.5 ATP, FADH = 1.5 ATP; for each glucose = 30(32) ATP
can NADH cross the mitochondrial membrane?
No
transporter in muscle
Glycerol-3 phosphate shuttle
transporter in liver and heart
malate-aspartate shuttle
oligomycin
binds to ATPase and blocks proton channel
uncouplers
disrupt the electrochemical gradient by the diffusion of protons across inner membrane, generating heat instead of producing ATP
thermogenin
uncoupling protein in brown adipose tissue.
thermogenin function
transports protons from cytosolic side of inner mitochondrial membrane back into the mitochondrial matrix without ATP generation, generating heat.
glycogenin
dimer that initiates glycogen synthesis by catalyzing the attachment of glucose to a tyrosine residue on itself
enzymes for synthesis of glycogen
glycogen synthase, branching enzyme
glycogen synthase
UDP-Glucose used to add a glucose residue to main chain. a-1,4 linkage
branching enzyme
breaks a-1,4 linkage and forms a-1,6 linkage. transfers 7 glucose residues at a time
substrates for glycogen synthesis
UDP-glucose
UDP-Glucose
used to add glucose to main glycogen chain
enzymes used during glycogen degradation
glycogen phosphorylase, debranching enzyme (transferase, and a-1,6 glucosidase)
glycogen phosphorylase
uses phosphate to break a-1,4 linkage and release glucose 1-phosphate. continues until 4 residues are left
debranching enzyme
bifunctional enzyme, transferase and a-1,6 glucosidase
transferase enzyme
transfers 3 glucose residues leaving single glucose linked via a-1,6 linkage
a-1,6 glucosidase
release of the a-1,6 linked glucose as free glucose by hydrolysis reaction
products of glycogen degradation
glucose 1-phosphate and free glucose
t/f: glucose 6-phosphate can travel in blood
false. needs to be converted to free glucose by glucose 6-phosphatase found only in liver
glycogen phosphorylase regulation
inactive when dephosphorylated, active when phosphorylated
glycogen synthase regulation
inactive when phosphorylated, active when dephosphorylated
glycogen degradation promoted by hormones
glucagon and epinephrine
regulation of glycogen metabolism by glucagon and epinephrine
hormones bind to receptors and activate adenylate cyclase --> elevated cAMP activates protein kinase A (PKA) --> degradation of glycogen by activating phosphorylase and inhibition of glycogen synthesis by inhibiting synthase
insuline promotes glycogen synthesis
activates PPI --> deactivates phosphorylase kinase & phosphorylase, and activates glycogen synthase
where does the breakdown of glycogen to glucose occurs?
liver and muscle by phosphorolysis
rate limiting step in fatty acid synthesis
acetyl coa --> malonyl coa
enzyme in rate limiting step of fatty acid synthesis
acetyl coa carboxylase with cofactor biotin
fatty acid synthesis characteristics
NADPH is the reductant, at the end two carbons are added, cytoplasm, intermediates linked to ACP, enzymes joined in single polypeptide chain (fatty acid synthase), require energy, regulation: acetyl coa carboxylase
beta-oxidation characteristics
NAD and FAD are the oxidants, mitochondria, intermediates linked to coenzyme A, enzymes different polypeptides, yield energy, regulation: acetyl coa availability
fatty acid synthesis process
condensation - reduction (NADPH) - dehydration - reduction (NADPH)
acetyl coa carboxylase regulation
activated by: citrate, high insulin, induction (fed state)
inactivated by: long fatty acid chains, low energy charge, induction (starvation state)
beta-oxidation regulation
inhibition of carnitine acyl tranferase, availability of substrates, stimulation of adipose tissue lipases
ketone bodies
produced from acetyl coa when fat breakdown predominates
T/F: liver can use ketone bodies
false. because it lacks the enzyme beta-ketoacyl-CoA transferase
beta hydroxybutyrate
ketone body that can be used by muscles and reform acetyl coa for metabolism by citric acid cycle
glycolysis takes place in
cytosol
rate limiting steps of glycolysis
hexokinase, PFK-1, pyruvate kinase
hexokinase
glucose + ATP --> glucose 6-phosphate + ADP
PFK-1 (Phosphofructokinase 1)
committed step // F6P + ATP --> F1,6BP + ADP
pyruvate kinase
final step // phosphoenolpyruvate + ADP --> pyruvate +ATP
Hexokinase regulation
inhibited by: glucose 6-phosphate
PFK-1 regulation
activators: AMP, F2,6-BP
inhibitors: ATP, citrate and H+
Pyruvate kinase regulation
activator: F1,6-BP
inhibitors: ATP and alanine
regulation in liver
high glucose -> inc F2,6BP -> inc glycolysis
starvation -> dec F2,6BP -> inc gluconeogenesis
overall function of glycolysis
to convert glucose into two molecules of pyruvate
ATP and NADH produced during glycolysis
4 ATP - 2 used, 2 NADH
substrate level phosphorylation vs oxydative phosphorylation
SLP during glycolysis, refers to the phosphorylation of ADP to ATP independent of electron transport.
ox ph is the process in which ATP is formed as a result of the transfer of electrons from NADH/FADH2 to O2 by a series of electrons carriers
products produced during anaerobic conditions in glycolysis
lactate acid (humans, ethanol (non-humans) + energy
products produced during aerobic conditions in glycolysis
CO2 + H2O + energy
citric acid cycle substrates
can i keep selling sex for money, officer?
citrate, isocitrate, alpha-ketoglutarate, succinyl-coa, succinate, fumarate, malate, oxaloacetate
Citric acid cycle enzymes
so again david dances silly dances for diana
citrate Synthase, Aconitase, isocitrate Dehydrogenase, alpha-ketoglutarate Dehydrogenase, succinyl-CoA Synthetase, succinate Dehydrogenase, Fumarase, malate Dehydrogenase
key regulatory enzymes of citric acid cycle
citrate synthase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase
citrate synthase regulation
inhibited by: citrate and ATP
isocitrate dehydrogenase regulation
activated by: ADP
inhibited by: ATP and NADH
alpha-ketoglutarate dehydrogenase
inhibited by: succinyl coa, ATP, and NADH
pyruvate dehydrogenase regulation
inhibited by acetyl coA, NADH, and ATP
pyruvate dehydrogenase cofactors
thiamine phytophosphate, lipoamide, and FAD
thiamine phytophosphate
oxidative decarboxylation of pyruvate
lipoamide
transfers acetyl group to CoA
FAD as cofactor for pyruvate dehydrogenase
regenerates oxidized lipoamide
one round of citric acid cycle yields:
1 GTP, 3NADH, 1 FADH2, 2 CO2
Gluconeogenesis
synthesis of glucose from non-carbohydrate precursors such as (aa) alanine, lactate and glycerol
gluconeogenesis vs glycolysis
gluconeogenesis is not a direct reversal of glycolysis, but there are three reactions bypassed
first bypass reaction of gluconeogenesis
pyruvate -pyruvate carboxylase-> OAA -PEP carboxykinase-> PEP
pyruvate carboxylase cofactor
biotin
allosteric activator of pyruvate carboxylase
acetyl coa. high acetyl coa signals need for OAA
second bypass reaction of gluconeogenesis
F1,6-BP + H2O --F1,6-BPase-> F6-P + Pi
third bypass reaction of gluconeogenesis
glucose 6-ph + H2O --glucose 6-phosphatase--> glucose + Pi
transport of oxaloacetate out of mitochondria to the cytosol
since pyruvate carboxylase is the only enzyme of gluconeogenesis found in the mitochondria, OAA needs to be converted into malate (by NADH-linked malate dehydrogenase), exit the mitochondria via malate transporter and then be converted back to OAA by NAD-linked malate dehydrogenase in the cytosol
cori cycle purpose
pyruvate and NADH accumulates in muscles during anaerobic glycolysis so lactate is produced. NAD+ is required for glycolysis to continue, so lactate is transported to liver, converted back to glucose and returned to muscles (check)
pentose phosphate pathway
generates:
- NADPH for fatty acid synthesis
- ribose-5-ph for DNA, RNA and nucleotide synthesis
- sugar phosphate intermediates for glycolytic and gluconeogenesis pathways
branches of PPP:
Oxidative branch
non-oxidative branch
oxidative branch of PPP:
enzyme glucose 6-ph dehydrogenase converts: glucose 6-ph into ribulose 5-ph with the formation of 2 molecules of NADPH

enzyme phosphopentose isomerase converts ribulose 5-ph into ribose 5-ph
non oxidative branch of PPP:
Excess ribose-5-phosphate is converted to glycolytic intermediates glyceraldehyde-3-ph and fructose-6-ph

enzymes: 2 transketolases & 1 transaldolase
products of non-oxidative branch of PPP
can be used as intermediates to other pathways
biosynthesis of cholesterol
cholesterol synthesized from acetyl coA
rate limiting step in cholesterol biosynthesis
occurs in the ER, HMG-CoA reductase
HMG-CoA Reductase regulation
synthesis of ketone bodies,
- high levels of glucagon phosphorylates it and turns it off
- high levels of insulin dephosphorylates it and activates it
- inc [steroids] --> activation of proteolytic degradation of enzyme
- mRNA level regulated by cholesterol level: low cholesterol inc mRNA;
high cholesterol dec mRNA
statins
inhibit cholesterol synthesis by competitive inhibition for the active site of HMG-CoA reductase
synthesis of bile salts
- exclusively in liver
RLS: cholesterol converted to 7alpha-hydroxycholesterol by 7alpha-hydroxylase.
- uses NADPH
- inhibited by bile salts
steroid hormones derived from cholesterol
cholesterol is converted to pregnenolone
- requires 3 NADPH and O2
pregnenolone
precursor of all steroids
amino acid metabolism
proteins are broken down to AA
- alpha-amino group is removed and excreted as urea
- remaining c-skeleton used as precursor
remaining c-skeleton from AA can be used as precursor for:
TCA cycle, gluconeogenesis, fatty acids and ketone bodies
transamination:
removal of alpha-amino group
- transfer alpha-amino group to alpha-ketoglutarate to form glutamate
- glutamate + NAD + H2O forms ammonia (NH4) and NADH
enzymes that transfer alpha-amino group fom AA to form alpha-keto acid
transaminases
- aspartate transaminase
- alanine transaminase
NH2 transported to liver for excretion by
alanine and glutamate
rate limiting step of urea cycle
formation of carbamoyl phosphate by carbamoyl phosphate synthethase 1
regulation of rate limiting step of urea cycle
carbamoyl phosphate synthethase 1
- requires 2 ATP, so ATP (+), ADP (-)
- increased ([S]) (+)
- allosteric: N-acetylglutamate (NAG) (+)
Lesch-Nyhan disease
X-linked, almost always men, compulsive, aggressive, self-mutilating behavior, elevated PRPP ->excess purines -> excess uric acid = gout + neuro symptoms
Lipoproteins transportation
transport fatty acids from the intestine to the peripheral tissues and to the liver
VLDL transportation
transport fatty acids from the liver to the surrounding tissues
apoproteins are recognized by
LDL receptors during endocytosis
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