The Citric Acid Cycle Flashcards
Where does the CAC Occur?
in the mitochondrial matrix
Acetyl-CoA -> Citrate
Catalyzed by citrate synthase
Irreversible reaction
Not regulated
-citrate inhibits but only at high concentrations
Citrate -> Isocitrate
Isomerization
Reversible
Isocitrate -> alpha-Ketoglutarate
Oxidative decarboxylation Irreversible reaction Energy capture (NADH) Catalyzed by isocitrate dehydrogenase Regulated
alpha-Ketoglutarate -> Succinyl CoA
Oxidative decarboxylation Irreversible Reaction Energy capture (NADH) Catalyzed by alpha-ketoglutarate dehydrogenase Similar to PDH reaction Regulated
Succinyl-CoA
High energy intermediate (thioester)
Succinyl-CoA -> Succinate
Substrate-level phosphorylation
Reversible reaction
Energy Capture (NTP)
Succinate -> Fumarate
Oxidation Reversible reaction Catalyzed by succinate dehydrogenase FAD/FADH2 oxidation of C-C single bond Integral membrane protein (Complex II)
More about Succinate Dehydrogenase Complex
FADH2 is reoxidized by donating electrons to coenzyme Q
QH2 is reoxidized in the electron transport chain
Succinate dehydrogenase is a membrane-bound enzyme and is part of complex II in the ETC
Fumarate -> Malate
Hydration
Reversible reaction
Malate -> Oxaloacetate
Oxidation
Reversible reaction
Energy capture (NADH)
Regenerates oxaloacetate
Regulation of the Citric Acid Cycle
Cyclic, no rate-limiting steps per se
- affected by NAD+/NADH ratio
- regulated enzymes
- affected by concentrations of intermediates
Regulated Enzymes in the CAC
Isocitrate dehydrogenase
alpha-ketoglutarate dehydrogenase
Inhibitors and Activators of the CAC
Inhibitors: NADH, ATP
Activators: ADP, Ca++
High levels of citrate
Inhibits citrate synthase
What does NADH inhibit?
Isocitrate dehydrogenase
alpha-ketoglutarate dehydrogenase
What does ATP inhibit?
Isocitrate dehydrogenase
What does ADP activate?
Isocitrate dehydrogenase
What does Ca++ activate?
alpha-ketoglutarate dehydrogenase
How to slow down the PDC and the CAC
Decreased ADP in the matrix = decreased activity of ATP synthase = increased H+ gradient across IMM = decreased rate of electron transport = decreased oxidation of NADH = decreased NAD+/NADH ratio
ATP synthase is not using a gradient
Decrease in O2 consumption
How to speed up the PDC and the CAC
Increased ADP in the matrix = increased activity of ATP synthase = decreased H+ gradient across IMM = increased rate of electron transport = increased oxidation of NADH = increased NAD+/NADH ratio
ATP synthase using a gradient
Increase in O2 consumption
The CAC is both catabolic and anabolic
Amphibolic
CAC intermediates can be used in the synthesis of amino acids, carbs, fats, nucleotides, and other compounds
Anaplerotic Reactions
Replenish citric acid cycle intermediates
-intermediates may be consumed in other processes
-must be adequate intermediates to continue CAC
Many reactions may be anaplerotic
-amino acid breakdown
-pyruvate carboxylase
Pyruvate Carboxylase Catalyzes an Anaplerotic Reaction
The formation of oxaloacetate from pyruvate is an important anaplerotic reaction
The reaction is catalyzed by pyruvate carboxylase
This enzyme is activated by acetyl-CoA and inhibited by ADP
Functions of the CAC
Provide biosynthetic precursors
An important step in the generation of ATP
-CAC generates 10 ATP per acetyl-CoA
-complete aerobic oxidation of glucose yields 32 ATP
ATP yield under aerobic conditions
Glycolysis -2 net ATP -2 NADH = 5 ATP Pyruvate -2 NADH = 5 ATP CAC -6 NADH = 15 ATP -2 FADH2 = 3 ATP -2 GTP = 2 ATP
