Mnemonic: Our City Is Kept Safe And Sound From Malice
- Oxaloacetate
Citrate synthase
- Citrate (may leave the mitochondria to enter CITRATE SHUTTLE for fatty acid synthesis)
Aconitase (Aconitic acid is a dehydrated citric acid)
- Isocitrate
Isocitrate dehydrogenase (dehydrogenated H+ added to NAD to form NADH & CO2) Major control enzyme (inhibited by NADH & ATP & activated by ADP)
- α-Ketoglutarate
α-Ketoglutarate dehydrogenase (dehydrogenated H+ added to NAD to form NADH & CO2) Similar to pyruvate dehydrogenase (requires thiamine, lipoic acid, CoA, FAD, NAD) Lack of thiamine slows oxidation of acetyl-CoA in citric acid cycle
- Succinyl-CoA (also for heme synthesis & ketone body activation in extrahepatic tissues)
Succinyl-CoA synthetase (GDP+Pi = GTP - substrate level phosphorylation) Also, called Succinate thiokinase
- Succinate
Succinate dehydrogenase (dehydrogenated H+ added to FAD to form FADH2) On mitochondrial membrnae (complex II of Electron Transport Chain)
- Fumarate
Fumarase
- Malate (can leave mitochondria to enter MALATE SHUTTLE for gluconeogenesis)
Malate dehydrogenase (H+ exchanged between NAD and NADH)
- Oxaloacetate
Remember the enzymes of the cycle:
All the enzymes are in the matrix of mitochondria except succinate dehydrogenase which is in inner mitochondrial membrane.
- 2 “substrate”-ase: ACONITASE and FUMARASE
- 2 “sythase/synthetase”: CITRATE SYNTHASE and SUCCINYL-COA SYNTHETASE
- Others “dehydrogenases”: ISOCITRATE DEHYDROGENASE, α-KETOGLUTARATE DEHYDROGENASE, SUCCINATE DEHYDROGENASE, MALATE DEHYDROGENASE
In short, Kreb’s cycle is
Acetyl-CoA——————————————→ 2 CO2
3 NAD + FAD + GDP + Pi 3 NADH + FADH2 + GTPFunction: Oxidation of Acetyl-CoA to CO2 with release of energy (NADH, FADH2, GTP)
Acetyl-CoA is yielded from glucose, fatty acids, ketone bodies, ketogenic amino acids and alcohol.
Pyruvate from aerobic glycolysis enters mitochondria, where it may be converted into acetyl-CoA (irreversible reaction) under the action of enzyme Pyruvate Dehydrogenase (PDH – inhibited by it’s product acetyl-CoA) for entry into:
- If ATP is needed: Citric acid cycle
- If ATP is sufficient: Fatty acid synthesis
PDH includes cofactors and conenzymes. Easy way to remember this is – they are vitamin B or vitamin B like:
- Vitamin B1 – Thiamine (Thiamine Pyrophosphate/TPP) for PDH (E1)
- Vitamin B like – Lipoic acid for Acetyl Transferase (E2)
- Vitamin B5 – Panothenic acid (CoA/Cofactor A) for E2
- Vitamin B2 – Riboflavin (FAD) for E3
- Vitamin B3 – Nicotinamide (NAD) for E3
Another Mnemonic: Citrate Is Kreb’s Starting Substrate For Making Oxaloacetate
- Citrate
- Isocitrate
- Alpha-Ketoglutarate
- Succinyl CoA
- Succinate
- Fumarate
- Malate
- Oxaloacetate
Alcoholism and Hypoglycemia:
- Poor nutrition
- High NADH from alcohol and acetaldehyde dehydrogenase favors formation of:
- Lactate from pyruvate
- Malate from oxaloacetate
- Glycerol-3-phosphate from Dihydroxyacetone phosphate
![dr. sulabh kumar shrestha](https://epomedicine.com/wp-content/uploads/2020/07/profile.jpg)
He is the section editor of Orthopedics in Epomedicine. He searches for and share simpler ways to make complicated medical topics simple. He also loves writing poetry, listening and playing music.