TCA cycle Flashcards
What are the 3 stages of the TCA cycle?
Acetyl CoA production
Acetyl CoA oxidation
Electron transfer and oxidative phosphorylation
Where in teh cell does the TCA cycle occur?
The matrix of the mitochondria
How is citrate formed?
Acetyl CoA joins with oxaloacetate to form citrate
How many redox reactions occur per turn of the cycle?
4
How many NADH molecules are produced per cycle?
3
How many FADH molecules are produced per cycle?
1
What are the functions of the TCA cycle?
Metabolism of all fuels
Participates in gluconeogenesis
Provides energy and metabolites for cell metabolism
Conversion of carbohydrates to fat
Source of non-essential amino acids (E&D)
What enters the TCA cycle?
Acetyl CoA
What is acetyl CoA the end product of?
Glycolysis
Beta-oxidation
Amino acid catabolism
What enzyme catalyses oxidative decarboxylation of pyruvate?
Pyruvate dehydrogenase
What does the oxidative decarboxylation of pyruvate form?
CoEnzyme A
What 5 coenzymes are needed for the oxidative decarboxylation of pyruvate?
TPP
Lipoyllysine
FAD
NAD
Acetyl CoA
What does Coenzyme A do?
Carries acyl groups and thioesters
What does high [ATP] mean?
Energy needs of the cell are being met
What does high [pyruvate] mean?
Cell requires energy
What steps of oxidative decarboxylation of pyruvate are regulated by enzyme 1?
Decarboxylated of pyruvate to an aldehyde
Oxidation of the aldehyde to a carboxylic acid
What steps of oxidative decarboxylation of pyruvate are regulated by enzyme 2?
Formation of acetyl CoA
What steps of oxidative decarboxylation of pyruvate are regulated by enzyme 3?
Reoxidation of lipoamide cofactor
Regeneration of the oxidised FAD cofactor - NADH produced
How is the condensation of oxaloacetate with acetyl CoA regulated?
Tightly, controlled step which is required for the cycle
What are the intermediates of the TCA cycle?
Citrate
Isocitrate
Alpha-ketoglutarate
Succinyl CoA
Succinate
Fumarate
L-Malate
Oxaloacetate
What step(s) result in decarboxylation and NADH production?
Isocitrate to alpha-ketoglutarate
Alpha-ketoglutarate to succinyl CoA
What happens during the conversion of succinyl CoA to succinate?
Substrate level phosphorylation forming GTP
What step produces FADH2?
Succinate to fumarate
What step results in ONLY the production of NADH?
L-malate to oxaloacetate
What does high citrate concentrations mean?
Cell energy requirements are met
What does the activity of the TCA cycle depend on?
Availability of NAD+ for the dehydrogenase reaction
Oxaloacetate and citrate concentrations
Pyruvate dehydrogenase activity
Citrate synthase activity
Isocitrate dehydrogenase activity
Alpha-ketoglutarate dehydrogenase activity
What is the general regulatory mechanisms of the TCA cycle?
Activated by substrate availability
Inhibited by product accumulation
NADH and ATP inhibit
NAD+ and ADP activate
What is the general regulatory mechanisms of the TCA cycle?
Activated by substrate availability
Inhibited by product accumulation
NADH and ATP inhibit
NAD+ and ADP activate
What is the general regulatory mechanisms of the TCA cycle?
Activated by substrate availability
Inhibited by product accumulation
NADH and ATP inhibit
NAD+ and ADP activate
What is needed for dehydrogenase reactions?
NAD+
What does citrate synthase do?
Converts oxaloacetate and acetyl CoA to citrate
What happens to citrate synthase during fasting?
[ATP] and [NADH] increase
Equilibrium between L-malate: oxaloacetate pushes towards L-malate
Malate is used for gluconeogenesis in cytosol
Acetyl CoA used for ketone synthesis due to lack of oxaloacetate
What kind of enzymes regulate the TCA cycle and what are their names?
Exergonic
Citrate synthase
Isocitrate dehydrogenase
Alpha-ketoglutarate dehydrogenase
What are the enzymes regulating the TCA cycle regulated by?
Energy indicators
Product accumulation
Substrate availability
What downregulates pyruvate dehydrogenase?
Pyruvate dehydrogenase kinase
What activates pyruvate dehydrogenase kinase?
Acetyl CoA
NADH
What inactivates pyruvate dehydrogenase kinase?
Pyruvate
ADP
Ca++
K+
What upregulates pyruvate dehydrogenase?
Pyruvate dehydrogenase phosphatase
What activates pyruvate dehydrogenase phosphatase?
Ca++
Mg++
Where is isocitrate dehydrogenase found in the cell?
Cytosol
Mitochondria
What inhibits isocitrate dehydrogenase?
ATP & NADH
What stimulates isocitrate dehydrogenase?
ADP, NAD+, Ca++
How does isocitrate dehydrogenase behave in the absence of ADP?
Basically inactive
What happens due to isocitrate dehydrogenase?
Decarboxylation
NADH production
What stimulates alpha-ketoglutarate dehydrogenase?
Ca++
What inhibits alpha-ketoglutarate dehydrogenase?
ATP
Succinyl CoA
NADH
What occurs due to the activity of alpha-ketoglutarate dehydrogenase?
Decarboxylation
NADH produced
How are 4 carbon intermediates formed?
Carboxylation of 3 carbon precursors
