METABOLISM SYLLABUS 4: TCA Cycle (aka Krebs Citric Acid Cycle) Flashcards
where does TCA cycle occur
what is the nature of it?
in mitochondria of all aerobic cells
irreversible
what is the net reaction of the TCA cycle
how many ATP are yielded per mole of Acetyl CoA that enters the TCA cycle?
10 ATP:
3 NADH -> 7.5 ATP
FADH2 -> 1.5 ATP
is there any net removal or addition of TCA intermediates?
no
which reactions of the TCA cycle are irreversible?
STEP 1: citrate synthase reaction
what inhibits the citrate synthase reaction of the TCA cycle?
STEP 1
ATP, NADH - signs of high energy - inhibit it
also inhibited by high levels of citrate, = product inhibition
what is the reversibility of step 2 of the TCA cycle?
aconitase converts citrate to isocitrate
this is reversible
citrate <-> cis-aconitate <-> isocitrate
what is the rate limiting step of the TCA cycle?
what regulates it?
STEP 3: isocitrate DH reaction
isocitrate undergoes oxidative decarboxylation
Co2 is released
NAD+ is reduced to NADH
results in aKg, alpha ketoglutarate
regulated by energy charge: stimulated by ADP - low energy charge - and inhibited by ATP and NADH - high energy charge
what is the structure of the a-KGDH enzyme? what is its regulation as such?
E1, E2, E3, like in the PDH complex
E1 enzyme: aKg decarboxylase: has thiamine PP as a cofactor, decarboxylates aKg to Co2 + a 4C succinyl product
E1 is inhibited by ATP
E2: uses lipoid acid; transfers the 4C succinyl product to CoASH
E2 is inhibited by succinyl CoA
E3: uses FAD and NAD to regenerate oxidized lipoic acid for E2
E3 is inhibited by NADH
why is GTP, not ATP, produced during TCA cycle?
b/c occurs in the mito and the mito can make some of its own proteins, and they need GTP for ribosome assemblies and elongation factors and movements of mRNAs
GTP though is equivalent to ATP, can be converted easily
what reaction in the TCA cycle produces energy as GTP?
succinyl CoA synthase aka thiokinase takes succinyl CoA, makes succinate
takes GDP + Pi, releases GTP + CoASH
what is the purpose of steps 6-8 of the TCA cycle?
what enzymes do this?
convert succinate to OAA
succinate DH, fumarase, malate DH
what is the equilibrium of the malate DH reaction in vitro versus in vivo?
in vitro: greatly favors OAA -> malate
in vivo: OAA is continually being removed by citrate synthase rxn; this keeps [OAA] low; pulls rxn in direction toward OAA formation
what is the overall yield from G6P -> 6CO2?
detail where the ATP comes from
32 ATPs per G6P:
Glucose -> 2 pyruvate + 2 NADH = 2ATP
2NADH -> mito = 5 ATP
2 Pyruvate -> 2 Acetyl CoA + 2NADH
2NADH -> 5 ATP
2 Acetyl CoA -> 20 ATP
= 32 total ATP per G6P
is the TCA cycle a catbolic, anabolic, or amphibolic pathway?
amphibolic
what regulates the TCA cycle?
1) respiratory control: regulates oxidation of NADH and FADH2 by mito respiratory chain
2) energy charge: ATP inhibits citrate synthase, isocitrate DH, aKg DH
3) [OAA]: OAA is pulled out of cycle during gluconeogenesis, reduced to malate when NADH levels are elevated (aka after EtOH consumption)
what are the anabolic abilites of the TCA cycle?
1) Citrate -> fatty acid synthesis
2) Succinyl CoA -> heme synthesis
3) OAA and Malate -> glucose synthesis
4) OAA -> glucose, aspartate, asparagine, pyrimidines synthesis
what are the anaplerotic rxns of the TCA cycle?
reactions that occur if OAA is removed or if intermediates are pulled out such that OAA isn’t regenerated and the cycle stops as acetyl CoA accumulates
these reactions replenish the pulled-out OAA or deficient OAA
what are the analproetic reactions of the TCA cycle?
1) Pyruvate Carboxylase converts pyruvate -> OAA
2) many amino acids -> TCA cycle intermediates, or -> OAA directly
3) PEP carboxykinase converts PEP to OAA
what stimulates the analproetic pyruvate carboxylase reaction?
Acetyl CoA
occurs if acetyl CoA cannot enter the TCA cycle as OAA
what TCA cycle intermediate can glutamate become?
a-KG
what tca cycle intermediate can valine , isoleucine, methionine, threonine make?
succinyl CoA
what tca cycle intermediate can phenylalanine or tyrosine make?
fumarate
what tca cycle intermediate can aspartate make?
OAA
what are ATP and NADH effect on the TCA cycle
decrease citrate synthase, ICDH, a-KGDH
is acetyl CoA a limiting reactant in TCA cycle
not usually b/c also produced from oxidation of fatty acids, several amino acids, ethanol
