Biochemistry · Topic
Odd-chain fatty acids and propionate metabolism !
Odd-numbered fatty acids end as propionyl-CoA, which biotin and vitamin B12 turn into succinyl-CoA.
Updated 2026-11-01
Key facts
- The last β-oxidation turn of an odd-chain fatty acid leaves 1 propionyl-CoA (3 C) and 1 acetyl-CoA.
- Propionyl-CoA carboxylase (biotin, ATP) → D-methylmalonyl-CoA → racemase → L-methylmalonyl-CoA.
- Methylmalonyl-CoA mutase (adenosylcobalamin, B12) → succinyl-CoA, which enters the Krebs cycle.
- It is the only route by which part of a fatty acid gives net glucose.
In detail
- Sources of propionyl-CoA: odd-chain fatty acids (dairy, ruminant fat), valine, isoleucine, methionine, threonine, the cholesterol side chain and gut fermentation.
- Propionyl-CoA carboxylase adds CO₂ with biotin and forms D-methylmalonyl-CoA.
- Methylmalonyl-CoA epimerase converts it to the L isomer.
- Methylmalonyl-CoA mutase rearranges the skeleton to form succinyl-CoA; it needs vitamin B12 as adenosylcobalamin.
- Succinyl-CoA follows the Krebs cycle to oxaloacetate, which can go to gluconeogenesis.
- Also called
- Propionyl-CoA pathway, Methylmalonyl-CoA pathway
Clinical notes
- Propionic acidaemia (carboxylase missing): vomiting, acidosis, hyperammonaemia and ketosis in the newborn.
- Methylmalonic acidaemia (mutase or adenosylcobalamin synthesis missing): a similar picture with very high methylmalonic acid.
- Vitamin B12 deficiency: methylmalonic acid rises and helps tell it from folate deficiency (homocysteine rises in both).
Pathways
Related
Test yourself
Think of the answer, then tap the question to see it.
Which enzyme of the propionate pathway needs vitamin B12?
Methylmalonyl-CoA mutase, which uses adenosylcobalamin.
Which marker tells B12 deficiency from folate deficiency?
Methylmalonic acid, which rises in B12 deficiency but not in folate deficiency.
Which Krebs cycle intermediate does propionyl-CoA end up as?
Succinyl-CoA.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Propionyl-CoA catabolism (Reactome, 2026); Propionic acidemia: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Methylmalonic acidemia: MedlinePlus Genetics (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).
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Representative model, for educational purposes only.