TCA Cycle Flashcards
Where does the Tricarboxylic Acid (TCA) Cycle occur?
In the mitochondrial matrix
The TCA cycle is a part of
Cellular respiration (aerobic process)
The TCA consists of a series of ______ reactions that results in ________ to ___________
REDOX, oxidation of acetyl-CoA, 2 molecules of CO2
4C (OA) + 2C (acetyl) –>
6C (citrate)
Isomer of citrate is “oxidatively decarboxylated” to give
5C compound (alpha-Ketoglutarate)
5C compound (alpha-Ketoglutarate) –>
4C (succinate) via oxidative decarboxylation
OA is regenerated from
succinate (the cycle repeats)
Label
Properties of the TCA cycle:
- Aerobic
- Source of biosynthetic precursors
- Its activity depend of tissue type: Most active in brain, heart, kidney cortex, and liver
- Subcellular location: Enzymes within mitochondrial matrix except succinate dehydrogenase, which is located on the mitochondrial inner membrane.
- Compartmentalization - Inner mitochondrial membrane is impermeable to NADH, Acetyl CoA, Oxaloacetate; separate mitochondrial & cytosolic pools of each.
Enzymes of the TCA Cycle
- Citrate synthase
- Aconitase
- Isocitrate dehydrogenase
- Alpha-ketoglutarate dehydrogenase complex
- Succinyl-CoA synthetase
- Succinate dehydrogenase
- Fumarase
- Malate dehydrogenase
Pyruvate Dehydrogenase Complex (in mitochondrial matrix; not part of TCA cycle) consists of :
E1, pyruvate dehydrogenase (decarboxylation, TPP)
E2, dihydrolipoyl transacetylase (lipoamide, CoA)
E3, dihydrolipoyl dehydrogenase (FAD, NAD+)
Other components (regulatory): PDH kinase, protein phosphatase
Last 3 steps that constitute a common “metabolic motif”
Oxidation→hydration→oxidation
TCA Cycle is regulated:
- By energy charge: ATP, ADP
- By end product of the cycle: mitochondrial NADH
- At irreversible steps
Irreversible steps cataylized by
–citrate synthase
–isocitrate dehydrogenase (major)
–alpha-ketoglutarate dehydrogenase
Citrate synthase is allosterically regulated by
–NADH, succinyl-CoA, citrate, and ATP (inhibitors)
–ADP (activator)
Isocitrate dehydrogenase is allosterically regulated by
–ATP (inhibitor); calcium and ADP (activators)
Alpha-ketoglutarate dehydrogenase is regulated by
Succinyl-CoA and NADH (inhibitors) and calcium (activator)
Pyruvate Dehydrogenase is allosterically inhibited by:
- _________
- _________
- _________
and allosterically activated by:
- _________
- _________
- _________
Allosterically inhibited by:
- ATP
- Acetyl CoA
- NADH
Allosterically activated by:
- AMP
- CoASH
- NAD+
________ and ________stimulate PDH by promoting DEphosphorylation
Ca++, insulin
Pyruvate dehydrogenase (PDH) inhibited by reversible phosphorylation of __________:
- PDH kinase: allosterically activated by ________
- ______________
- serine residue on E1
- PHD kinases: allosterically activated by ATP
- Protein phosphatase
Intermediates are replenished through
anaplerosis
Anaplerotic enzymes:
- pyruvate carboxlase (major)
- PEPCK
- Malic enzyme
- PEP carboxylase (plants, bacteria)
A mutant form of IDH is present in ____________.
some cancers
