Citric Acid Cycle/TCA cycle Flashcards
What kind of process do cells need to generate ATP?
a process that generates electricity in the mitochondria
How do we create electricity?
electron-rich molecules must transfer electrons to chain of complexes (electron transport chain)
what is the final electron acceptor in ETC?
Oxygen!
electron donor molecules (2)
NADH
FADH2
how do we produce NADH and FADH2?
dehydrogenase enzymes!
in the citric acid cycle (Krebs cycle)
CAC overview
8 rxns
acetyl-coa –> CO2
oxidation of pyruvate to CO2
starving state (what is our source of acetyl-coa and what are hormone levels like)
increase in glucagon, epinephrine, and cortisol
fatty acids are source of acetyl-coa
fed state (what is our source of acetyl-coa and what are hormone levels like)
increase in insulin
have plenty of acetyl-coa from breaking down glucose (mainly), fructose, and galactose
in the liver (source of acetyl-coa?)
alcohol!
external sources of acetyl-coA?
proteins
CAC starting with glucose
1) glycolysis converts 1 glucose to 2 pyruvate
2) 2 pyruvate enter mitochondria
3) pyruvate dehydrogenase makes acetyl-CoA, CO2, and NADH (from NAD+)
*this links glycolysis and CAC
what inhibits isocitrate dehydrogenase
high ATP and high NADH inhibit isocitrate dehydrogenase
what stimulates isocitrate dehydrogenase
high ADP stimulates isocitrate dehydrogenase because it tells the cell more energy is needed
high Ca2+ levels (calcium rises during work, work requires energy)
rate-limiting step of CAC
isocitrate dehydrogenase step!
what does alpha-ketoglutarate dehydrogenase require to function?
5 cofactors T-rex Loves + Cares For Nachos 1. Thiamine (vitamin B1) 2. Lipoic acid 3. Coenzyme A (vitamin B5/pantothenate) 4. FAD+ (vitamin B2/riboflavin) 5. NAD+ (vitamin B3/niacin)
what can disrupt CAC?
vitamin deficiency
what else is succinate dehydrogenase a part of?
the ETC
it is complex II!
what do we do with oxaloacetate product?
oxaloacetate can join a new acetyl-CoA and start new cycle
control of CAC
speeds up when there is need for energy
slows down when there is a lot of energy
do hormones control CAC?
NO!
how does fatty acid synthesis fit into this?
Fatty acid oxidation produces acetyl-CoA which can enter CAC
pyruvate dehydrogenase complex
combines pyruvate with CoASH
1 CO2 released, 1 NADH produced
PDC enzymes and co-enzymes
pyruvate dehydrogenase (TPP) dihydrolipoyl transacetylase (lipoic acid and coenzyme A) dihydrolipoyl dehydrogenase (NAD and FAD)
TPP
decarboxylation of alpha-keto acids
NAD+
hyrdride transfer rxns
FAD+
flavin coenzymes exist in 3 redox states
coenzyme A
has reactive sulfhydryl group that carries acyl groups
very favorable
lipoic acid
couples acyl-group transfer with electron transfer
PDC is a…
multi-enzyme complex
they are catalytically efficient
series of rxns occurs more rapidly
regulation of PDC
product inhibition or covalent modification
regulation of PDC by product inhibition
high acetyl-CoA or NADH allosterically inhibit PDC
regulation of PDC by covalent modification
pyruvate dehydrogenase kinase is part of mammalian PDC
pyruvate dehydrogenase kinase is activated by NADH and acetyl-CoA (leads to phosphorylation and inactivation of E1)
citrate synthase regulation
oxaloacetate binds, induces conformational change and facilitates binding of acetyl-CoA
NADH and succinyl-CoA allosterically inhibit citrate synthase
fluoroacetate
converted to fluorocitrate (potent inhibitor of aconitase)
blocks TCA cycle
succinate dehydrogenase…why is it unique?
it’s the only membrane-bound enzyme in the CAC
FAD is covalently bound to it and electrons stored in FADH2 are sent directly to ETC
malate dehydrogenase rxn energy
very unfavorable
it occurs because citrate synthase rxn is very favorable
ATP from 1 glucose
38 ATP
glycolysis: 2ATP + 2NADH (2 ATP + 6 ATP = 8 ATP)
PDC: 1 NADH per pyruvate (3 ATP x 2 = 6 ATP)
TCA: 3 NADH + FADH2 + GTP per acetyl-CoA (9+2+1)x2 = 24
succinyl-CoA
feedback inhibitor of CAC
enzymes of TCA associate as…
a metabolon
channels substrates
enables higher metabolic flux
is CAC catabolic or anabolic?
catabolic bc endpoint is oxidative degradation of fuel
BUT, intermediates of CAC can be removed for biosynthetic processes (this makes it amphibolic - BOTH!)
cataplerotic reactions
reactions that use CAC intermediates
anaplerotic
reactions that replenish CAC intermediates
glyoxosomes
plants use glyoxylate cycle to synthesize sugars from acetyl-CoA and to make oxaloacetate (they also use TCA cycle)
