[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Biochemistry](https://durgical.com/en/biochemistry/) › Propionyl-CoA to succinyl-CoA [Biochemistry](https://durgical.com/en/biochemistry/) · Metabolic pathway # Propionyl-CoA to succinyl-CoA Odd-chain fatty acids and four amino acids leave propionyl-CoA. Three enzymes turn it into succinyl-CoA, which enters the Krebs cycle. Updated 2026-11-01 ## Interactive map **Balance:** ATP -1 CO₂ -1 ## Key facts - Propionyl-CoA comes from valine, odd-chain fatty acids, methionine, isoleucine and threonine (mnemonic VOMIT) and from the cholesterol side chain. - Propionyl-CoA carboxylase needs biotin and ATP and makes D-methylmalonyl-CoA. - Methylmalonyl-CoA mutase needs adenosylcobalamin (B12); it is one of only two human B12 enzymes, with methionine synthase. - Succinyl-CoA feeds the Krebs cycle and can become glucose: this is why the last three carbons of odd-chain fatty acids are glucogenic. - B12 deficiency raises methylmalonic acid; folate deficiency does not. **Also called** Propionate pathway ## Regulation - Flux follows supply: protein intake, fasting and gut bacteria, which make propionate, increase it. - No major allosteric control is known; activity depends on biotin and B12 status. ## The steps, one by one - **Step 1 · Propionyl-CoA carboxylase (PCC)** irreversible [Propionyl-CoA](https://durgical.com/en/biochemistry/molecules/propionyl-coa/) + CO₂ + [ATP](https://durgical.com/en/biochemistry/molecules/atp/) → D-Methylmalonyl-CoA + ADP + phosphate (Pi) Adds CO₂ (as bicarbonate) to propionyl-CoA using biotin and ATP, making D-methylmalonyl-CoA. **If it fails:** PCC deficiency (PCCA or PCCB genes): propionic acidaemia with ketoacidosis and hyperammonaemia in the newborn. [Propionic acidaemia →](https://durgical.com/en/conditions/propionic-acidaemia/) - **Step 2 · Methylmalonyl-CoA epimerase (MCEE)** D-Methylmalonyl-CoA ⇌ L-Methylmalonyl-CoA Turns the D form into the L form, the only one the mutase can use. **If it fails:** MCEE deficiency is rare and usually mild, with a modest rise of methylmalonic acid. - **Step 3 · Methylmalonyl-CoA mutase (MMUT), B12-dependent** L-Methylmalonyl-CoA ⇌ succinyl-CoA Moves the CoA-carbonyl group inside the molecule by a radical reaction of adenosylcobalamin, giving succinyl-CoA. **If it fails:** Mutase defects or faults in B12 processing cause methylmalonic acidaemia; dietary B12 deficiency raises methylmalonic acid less dramatically. [Methylmalonic acidaemia →](https://durgical.com/en/conditions/methylmalonic-acidaemia/) ## Clinical notes - Propionic acidaemia (PCC deficiency): neonatal ketoacidosis, hyperammonaemia and high propionylcarnitine (C3) on newborn screening. - Methylmalonic acidaemia (mutase or B12-cofactor defects): similar crises plus kidney damage; some forms respond to B12. - In B12 deficiency methylmalonic acid is a sensitive test; part of the nerve damage is blamed on abnormal fatty acids made from methylmalonyl-CoA. - Excess propionyl-CoA inhibits N-acetylglutamate synthase, which is why ammonia rises in these disorders. ## Pathways - [Propionyl-CoA to succinyl-CoA](https://durgical.com/en/biochemistry/pathways/propionyl-coa-to-succinyl-coa/) ## Related conditions - [Propionic acidaemia](https://durgical.com/en/conditions/propionic-acidaemia/) - [Methylmalonic acidaemia](https://durgical.com/en/conditions/methylmalonic-acidaemia/) - [Pernicious anaemia](https://durgical.com/en/conditions/pernicious-anaemia/) - [Hyperammonaemia](https://durgical.com/en/conditions/hyperammonaemia/) ## Related - [Propionyl-CoA](https://durgical.com/en/biochemistry/molecules/propionyl-coa/) - [Cobalamin (vitamin B12)](https://durgical.com/en/biochemistry/topics/cobalamin/) - [Biotin (vitamin B7)](https://durgical.com/en/biochemistry/molecules/biotin/) - [Odd-chain fatty acids and propionate metabolism](https://durgical.com/en/biochemistry/topics/odd-chain-fatty-acids-and-propionate-metabolism/) - [Krebs cycle (citric acid cycle)](https://durgical.com/en/biochemistry/pathways/krebs-cycle/) - [Fatty acid β-oxidation](https://durgical.com/en/biochemistry/pathways/fatty-acid-oxidation/) - [Gluconeogenesis](https://durgical.com/en/biochemistry/pathways/gluconeogenesis/) - [Branched-chain amino acid breakdown (leucine route)](https://durgical.com/en/biochemistry/pathways/branched-chain-amino-acid-breakdown/) - [Methionine cycle and transsulfuration](https://durgical.com/en/biochemistry/pathways/methionine-cycle-and-transsulfuration/) - [Urea cycle](https://durgical.com/en/biochemistry/pathways/urea-cycle/) ## Test yourself Think of the answer, then tap the question to see it. ## Which vitamins do the first and last steps need? Biotin for propionyl-CoA carboxylase and adenosylcobalamin (B12) for methylmalonyl-CoA mutase. ## Why does methylmalonic acid rise in B12 deficiency but not in folate deficiency? Methylmalonyl-CoA mutase needs B12, not folate; homocysteine, in contrast, rises in both deficiencies. ## Which sources feed propionyl-CoA? Valine, isoleucine, methionine and threonine, odd-chain fatty acids and the cholesterol side chain. ## Why do propionic and methylmalonic acidaemias cause hyperammonaemia? Propionyl-CoA inhibits N-acetylglutamate synthase, so CPS-I, the first urea cycle enzyme, loses its activator. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/biochemistry/pathways/propionyl-coa-to-succinyl-coa/) Educational information, not medical advice. For any symptom, see a health professional. Sources: [Methylmalonic acidemia: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/methylmalonic-acidemia/) (MedlinePlus, US National Library of Medicine, 2026); [Propionic acidemia: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/propionic-acidemia/) (MedlinePlus, US National Library of Medicine, 2026); [MMUT gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/mmut/) (MedlinePlus, US National Library of Medicine, 2026); [MCEE gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/mcee/) (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011). [← All of biochemistry](https://durgical.com/en/biochemistry/) ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/biochemistry/pathways/propionyl-coa-to-succinyl-coa/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/pathways/propionyl-coa-to-succinyl-coa/