TCA Cycle Flashcards
where does the citric acid cycle?
in mito
the oxidation of 2 carbon units will produce?
2 CO2 molecules
1 GTP
high nrg e-‘s ( NADH, FADH2)
characteristics of acetyl CoA
active form of acetate
obtained from 2 nrg nutrients – carbs, lipids, proteins
formation of acetyl coA from pyruvate
decarboxylation
oxidation
transfer acetyl group to CoA
rxns are coupled to preserve nrg to drive formation of NADH and acetyl CoA
MPC
mitochondrial pyruvate carrier
pyruvate uses to get into mito for aerobic glycolysis
PDC
pyruvate dehydrogenase complex
catalyzes the decarboxylation of pyruvate
pyruvate dehydrogenase rxn
requires 3 enzymes
—-E1, E2, E3
5 coenzymes
- –catalytic cofactors
1. thiamine pyrophosphate
2. lipoic acid
3. FAD - –stoichiometric cofactors
4. CoA
5. NAD+
PDH links glycolysis to TCA
converts pyruvate to acetyl CoA
pyruvate dehydrogenase regulation
regulated by
- -allosteric interactions
- -reverse phosphorylation
high [acetyl coA] inhibits E2
- products increase
- phosphorylation of E2
- accumulation of ADP and pyruvate activate phosphatases
the TCA occurs under ?
aerobic conditions
and produces more nrg from glucose than glycolysis
first step of TCA
condensation of 4-carbon oxaloacetate and 2-carbon acetyl group of acetyl coA
oxaloacetate reacts w/ acetyl coA + water = citrate and CoA
catalyzed by citrate synthase
citrate isomerizes …….
to isocitrate
hydroxyl group of citrate is not in proper location for oxidative decarboxylation
dehydra/hydration moves -OH via enzyme aconitase
intermediate product
cis-aconitase
aconitase
used to move the -OH group on citrate
isocitrate dehydrogenase
1st of 4 redox rxns
unstable intermediate = oxalosuccinate
—loses CO2 while bound to enzyme
**rate limiting step
isocitrate —-> a-ketoglutarate
a-ketoglutarate dehydrogenase
similar to pyruvate dehydrogenase
decarboxylate an a-ketoacid
and
creates a thioester linkage w/ CoA
rxn
a-ketoglutarate —> succinyl CoA
succinyl CoA synthetase
this is only step that directly yields a high nrg phosphor compound (GTP/ATP)
2 isozymic forms
- –1. in liver, produce GTP
- –2. in skeletal and heart muscles, produce ATP
rxn
succinyl CoA –> succinate
succinate dehydrogenase
catalyzes formation of fumarate while generating FADH2
located in inner mito memb - directly assoc w/ ETC
FADH2 is not released from enzyme but the e-‘s are passed to Co-Q in ETC
rxn
succinate —> fumarate
fumarase
catalyzes the hydration of fumarate to form L-malate
fumarate –> L-Malate
malate dehydrogenase
final step
- -oxidation of malate has + G nrg
- -enzyme specifically recognizes L-malate
rxn is driven by the consumption of its products
- oxaloacetate – by citrate synthase
- NADH – by ETC
list the rxns of the TCA
- oxaloacetate —> citrate
- —> isocitrate
- —> a-ketoglutarate
- —> succinyl CoA
- —> succinate
- —> fumarate
- —> L-Malate
- —> oxaloacetate
list the enzymes of TCA in order
citrate synthase aconitase isocitrate dehydrogenase a-ketoglutarate dehydro succinyl CoA synthetase succinate dehydrogenase fumarase malate dehydrogenase
list the byproducts of the rxns in the TCA
- H2O + S-CoA = CoA
- NAD+ = NADH + CO2 + H+
- NAD+ + CoA = NADH, CO2, H+
- GDP + Pi = GTP + CoA
- FAD = FADH2
- H2O in
- NAD+ = H+, NADH
citric acid cycle regulation
high [acetyl coA] directly inhibits PDH complex subunit E2
nrg charge of cell dictates PDH complex activity
—high nrg = neg feedback
TCA regulation – insulin
can stim fatty acid synthesis by activating phosphatases and increasing the conversion of pyruvate to acetyl CoA
which is the precursor for fatty acids
TCA regulation – citrate synthase step
citrate synthase prevents wasteful hydrolysis of acetyl coA
oxaloacetate binds to the enzyme first, then the enzyme changes configuration to bind acetyl coA
TCA regulation – isocitrate dehydrogenase step
allosterically stim by ADP
–enhances enzyme affinity for substrate
rxn product NADH also inhibits by directly displacing NAD+
control here leads to build up of citrate
which transports to cytosol
signals phosphofructokinase
glycolysis halts
TCA - regulation – a-ketoglutarate dehydrogenase complex step
complex similar to PDH
similar to PDH in regulation
–allosterically inhibited by its products = succinyl coA and NADH
control causes a-ketoglutarate to build up from enzyme inhibition
–can then instead be used for synthesis of AA and purine bases
why is TCA cycle Anaplerotic ?
Anaplerotic rxns provide intermediates for replenishing TCA cycle
2 major Anaplerotic rxns
- –degradation of AA
- –carboxylation of pyruvate
TCA intermediates used in anabolic functions
when nrg needs are met by other means, intermediates are drawn for biosynthesis of other molecules in dif pathways
cycle will restart by formation of oxaloacetate from pyruvate when lactic acid builds up in muscle
