TCA Cycle Flashcards
Where does the TCA cycle occur?
All reactions occur in mitochondria
What are the products of the TCA cycle?
- NADH
- FADH2 -> ETC (ATP)
- GTP
- CO2
What is Citrate synthesised from?
- Acetyl CoA (2C)
- Oxaloacetate (4C)
What enzyme synthesises citrate?
Citrate Synthase
What can inhibit citrate synthase?
ATP
What does citrate inhibit?
PFK1
What does citrate activate?
ACoA carboxylase (fatty acid synthesis)
What is used for gluconeogenesis in the fasting state?
Oxaloacetate
this lowers the amount able to be used for TCA cycle
How is ketone synthesis triggered in the fasting state?
Oxaloacetate used for gluconeogenesis
- Less acetyl coA used for TCA cycle, build up
- Excess acetyl coA converted into ketones
What is isocitrate to citrate?
An isomer
What enzyme converts citrate to isocitrate?
Aconitase
What does fluoroacetate (rat poison) inhibit?
Aconitase
- Citrate -> Isocitrate
What is the rate-limiting step of the TCA cycle?
- Isocitrate
-> Co2 NADH
-> Alpha-ketoglutarate
(Enzyme: Isocitrate Dehydrogenase)
What enzyme converts Isocitrate to alpha-ketoglutarate?
Isocitrate Dehydrogenase
- Rate-limiting step
What inhibits alpha-Ketoglutarate?
- ATP
- NADH
What activates alpha-Ketoglutarate?
- ADP
- Ca2+
What are the irreversible steps of the TCA cycle?
Citrate synthase (oxaloacetate -> Citrate)
Isocitrate dehyrogenase
(Isocitrate -> alpha-ketoglutinate)
alpha ketoglutinate dehydrogenase
(a-KG -> Succinyl CoA)
What enzyme converts alpha ketoglutarate to Succinyl-CoA?
alpha-KetoGlutinate Dehydrogenase
What inhibits alpha-KetoGlutinate Dehydrogenase ?
- Succinyl-CoA (product)
- NADH
What stimulates alpha-KetoGlutinate Dehydrogenase ?
Ca2+
What is taken off of alpha ketoglutarate and added to it to make Succinyl-CoA?
- CoA added
- CO2 and NADH taken off
What is taken off of Succinyl-CoA to make Succinate?
- CoA
- GTP
What enzyme converts succinyl-CoA into Succinate?
Succinyl-CoA synthase
What enzyme converts Succinate to fumarate?
What is significant?
Succinate dehydrogenase
- Embedded in mitchondrial membrane
- Function as complex II electron transport
What molecule is also produced from Succinate dehydrogenase?
FADH2 (FAD+ the other way)
What other pathways (other than TCA) can produce fumarate?
- Urea cycle
- Purine synthesis (formation of IMP)
- Amino acid breakdown (phenylalanine, tyrosine)
What converts malate into fumarate?
Fumarase
What converts Malate into NADH and Oxaloacetate?
Malate dehydrogenase
What are the 2 major functions of malate/
- Transfer of NADH into mitochondria
- Transfer of oxaloacetate OUT of mitochondria
How does malate transfer NADH?
Oxaloacetate -> Malate
NADH-> NAD+ (electrons donated to malate)
- Malate then transported into mitochondria
- Malate converted to oxaloacetate making a molecule of NADH from NAD+
How is oxaloacetate replinshed in the cytosol when used in malate shuttle?
Oxaloacetate converted to aspartate (Glut-> a-KG)
- Aspartate then shuttled across
- Aspartate trnasfered to OAA (glut-> a-KG)
Describe how oxaloacetate can be transfered out of the mitochondria to participate in gluconeogensis?
OAA -> Malate (NADH -> NAD+)
- Malate transfered out of mitochondria
- Malate converted to OAA (NAD+ -> NADH)
What is citrate also used for?
Fatty acid synthesis
What is alpha-Ketoglutarate also used for?
Amino acid synthesis
What is Oxaloacetate also used for?
- Amino acid synthesis
- Glucose
What can succinyl coA be used for other than TCA cycle?
Heme synthesis
What can Succinyl-CoA be synthesised from?
- Methylmalonyl coA (from odd chain fatty acids and branched chain amino acids)
- a-KG (TCA cycle)
What are all the inhibitors of the TCA cycle?
- ATP
- NADH
- Acetyl-CoA
- Citrate
- Succinyl CoA
Signs of high energy
What is the TCA cycle activated by?
Ca2+ and ADP
