Citric Acid Cycle Flashcards
What are the three stages of Energy metabolism and cellular respiration?
Oxidation of precursors to yield Acetyl-CoA
Acetyl groups are oxidized to CO2 in CAC resulting in NADH and FADH2
Energy in NADH and FADH2 used to make ATP
Where is the majority of energy obtained?
Complete oxidation of pyruvate in the mitochondria
What are the four fates of pyruvate?
Lactate
Alanine
Acetyl CoA
Oxaloacetate
What happens to acetyl CoA in the CAC?
Completely oxidized to CO2 in CAC
What are the three enzymes in PDH?
Pyruvate Dehydrogenase
Dihydrolipoyl Transacetylase
Dihydrolipoyl Dehydrogenase
What 5 coenzymes are required for the PDH?
TPP
Lipoate
Coenzyme A
FAD+
NAD+
How is the PDH complex regulated by phosphorylation?
Inactivated by phosphorylation
Activated by dephosphorylation
What activates PD kinase?
Allosteric: NADH, Acetyl CoA
Glucocorticoids, Insulin, Growth and Thyroid hormones, Tyr kinases
What inhibits PD kinase?
Pyrvate, NAD, CoA
What activates PD phosphatase?
Calcium, Low NADH/NAD ratio, Low Acetyl CoA levels
What is generated in each turn of the CAC?
3 NADH
1 FADH2
One GTP
2CO2
What is the first reaction?
Citrate Synthase - formation of citrate
Rate limiting step
Irreversible
What is the second reaction?
Aconitase - formation of Isocitrate
Good substrate for oxidation
Reversible - product concentration kept low to pull forward
What is the third reaction?
Isocitrate Dehydrogenase - formation of a-ketoglutarate
Oxidative decarboxylation
Generates CO2 and NADH
Irreversible
What is the fourth reaction?
a-ketoglutarate dehydrogenase - forms Succinyl-CoA
Needs same five coenzymes used in PDH complex
Generates NADH
Irreversible
Where do the carbons lost as CO2 come from?
Derived from oxacloacetate
What is the fifth reaction?
Succinyl-CoA Synthetase - forms Succinate
Produces GTP
Reversible
What is the sixth reaction?
Succinate Dehydrogenase - forms fumarate
Bound to inner membrane, part of ETC
Produces FADH2
Reversible
What is the seventh reaction?
Fumarase - forms L-malate
Reversible
What is the eighth reaction?
Malate Dehydrogenase - forms oxaloacetate
Unfavorable - oxaloacetate concentration kept very low by citrate synthase
What are some examples of anaplerotic reactions that provide the CAC with intermediates to continue?
Pyruvate carboxylase - pyruvate to OAA
Malic Enzyme - Pyruvate to malate
PEP carboxykinase - PEP to OAA
How do glucogenic amino acids contribute to the TCA cycle?
Degradation generates 3,4, or 5C intermediates of the TCA cycle
How is citrate synthase regulated?
Activated: ADP
Inhibited: NADH, Succinyl-CoA, citrate ATP
How is Isocitrate dehydrogenase regulated?
Activated: Ca, ADP
Inhibited: ATP
How is a-ketoglutarate dehydrogenase complex regualted?
Activated: Ca
Inhibited: Succinyl-CoA, NADH
What results from citric acid cycle defects?
Invariably affects the CNS
Wide range of phenotypes
Diagnosis depends on biochemical analysis
Extremely rare
