Chapter 17: The Citric Acid Cycle Flashcards
Pyruvate dehydrogenase complex
A group of 3 enzymes and 5 coenzymes
Oxidizes pyruvate to acetyl-CoA & one CO2
Produces one NADH
Pyruvate dehydrogenase complex inhibition
The key means of regulating the complex is covalent modification via phosphorylation
PDH is allosterically inhibited by:
- ATP
- NADH
- acetyl CoA
- High ATP:ADP ratio
PDH is activated by:
- ADP
- NAD+
- Pyruvate
- Low ATP:ADP ratio
Citric acid cycle enzymes
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- Citrate synthase
- Inhibited by citrate and ATP
- Aconitase
- Isocitrate dehydrogenase- rate limiting
- Inhibited by NADH
- Stimulated by ADP and Ca2+
-
a-ketoglutarate dehydrogenase
- Inhibited by NADH, succinyl CoA, and acetyl CoA
- Stimulated by Ca2+
- Succinyl CoA synthetase
- Succiniate dehydrogenase
- Fumarase
- Malate dehydrogenase
Citric acid cycle intermediates
Intermediates
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- Citrate
- Isocitrate
- a-Ketoglutarate
- Succinyl CoA
- Succinate
- Fumarate
- Malate
- Oxaloacetate
Step 1 of CAC
Citrate synthase catalyzes the condensation of acetyl CoA and oxaloacetate to form citrate
Inhibited by:
- ATP
- NADH
- Succinyl-CoA
- Citrate
Step 2 of CAC
Aconitase catalyzes a dehydration that forms the intermediate cis-aconitate
Cis-aconitate is subsequently hydrated to form isocitrate
Step 3 of CAC
Isocitrate dehydrogenase catalyzes the oxidative decarboxylation of isocitrate forming α-ketoglutarate
Produces one molecule of NADH
Releases one molecule of CO2
Inhibited by:
- ATP
- NADH
Stimulated by:
- ADP
- NAD+
Step 4 of CAC
The α-ketoglutarate dehydrogenase complex catalyzes the synthesis of succinyl CoA
Produces one molecule of NADH
Releases one molecule of CO2
Inhibited by:
- ATP
- NADH
- Succinyl-CoA
The enzyme is an organized assembly of three kinds of enzymes that is homologous to the pyruvate dehydrogenase complex
Step 5 of CAC
Succinyl CoA synthetase catalyzes the cleavage of a thioester linkage forming succinate
Concomitantly forms one molecule of ATP/GTP via substrate-level phosphorylation
Step 6 of CAC
Succinate dehydrogenase performs an elimination reaction that forms a E alkene fumarate
Produces one molecule of FADH2
Step 7 of CAC
Fumarase performs a hydration reaction that introduces the only chiral CAC intermediate malate
Step 8 of CAC
Malate dehydrogenase oxidizes malate to reform oxaloacetate
Produces one molecule of NADH
Citric acid cycle phases and net products
Pyruvate oxidation- yields one NADH, one acetyl CoA, and one CO2 as waste
Citric acid cycle- yields one ATP, three NADH, one FADH2, and two CO2 as waste
Inputs and outputs shown are for each pyruvate molecule thus, each glucose molecule nets:
- 2 ATP
- 8 NADH
- 2 FADH2
Yields of each stage of cellular respiration
Per molecule of glucose
Glycolysis
- 2 ATP via substrate-level phosphorylation
- 2 NADH
- 2 Pyruvate
Pyruvate oxidation
- 2 NADH
- 2 Acetyl CoA
Citric acid cycle
- 2 ATP via substrate-level phosphorylation
- 6 NADH
- 2 FADH2
Oxidative phosphorylation
- Roughly 26-28 ATP
Total ATP
Maximum 30-32 ATP
Control points of CAC
CAC source for fatty acids and sterols
Citrate
CAC source for glutamate and purines
α-Ketoglutarate
CAC source for porphyrins & heme
Succinyl-CoA
CAC source for aspartate purines, pyrimidines, & glucose
Oxaloacetate
Anapleurotic reactions
Anaplerosis is the act of replenishing TCA cycle intermediates that have been extracted for biosynthesis (in what are called anaplerotic reactions).
The TCA cycle is a hub of metabolism, with central importance in both energy production and biosynthesis. Therefore, it is crucial for the cell to regulate concentrations of TCA cycle metabolites in the mitochondria. Anaplerotic flux must balance cataplerotic flux in order to retain homeostasis of cellular metabolism