BCKD kinase phosphorylates and inhibits the branched-chain keto-acid dehydrogenase complex.
Pathway
Branched-chain amino acid catabolism
Homo sapiens · Cytosol & mitochondrial matrix (major oxidation in muscle) · 7 reactions
Leucine, isoleucine, and valine share transamination and oxidative decarboxylation steps, then diverge. Leucine is ketogenic; isoleucine is both ketogenic and glucogenic; valine is glucogenic. Their carbon enters metabolism as acetyl-CoA, acetoacetate, or succinyl-CoA.
REACTOME IDENTIFIERR-HSA-70895View source record ↗
Pathway scope
NETWORK MAPThree alternative amino-acid inputs diverge into distinct branches, and several intermediate reactions are grouped; no single net yield applies.
Overview
EXPLORE BY LEVELBranched-chain A small molecule cells use to build proteins. catabolism is a set of connected chemical steps in human cells. Leucine, isoleucine, and valine share transamination and oxidative decarboxylation steps, then diverge. Leucine is ketogenic; isoleucine is both ketogenic and glucogenic; valine is glucogenic. Their carbon enters metabolism as acetyl-CoA, acetoacetate, or succinyl-CoA.
WHY THE FLOW CHANGES
Compare fed and fasting Regulation
Branched-chain amino-acid breakdown is controlled at the shared BCKDH complex.
The mitochondrial phosphatase PPM1K activates the complex by dephosphorylation.
The three amino acids share an initial route but their carbon products diverge; tissue use varies.
This is an instructional map of selected reactions, not a complete inventory of every reaction in the body. Some steps are grouped; transport, alternate routes, tissue differences, or full molecule balances may be summarized. The Research notes explain this map’s specific limits.
Explore the reaction map and enzyme steps
Pathway map
GENERATED FROM STRUCTURED REACTIONSSelect a molecule or enzyme to inspect it. Select a step number to open its full reaction detail.
Shared first steps
Aminotransferase forms branched-chain keto acids, then the BCKDH complex oxidatively decarboxylates them.
Leucine branch
Leucine carbon proceeds through isovaleryl-CoA and the HMG-CoA branch to ketogenic products.
Isoleucine branch
Isoleucine yields acetyl-CoA and propionyl-CoA, which can feed succinyl-CoA.
- Step 5Irreversible
Valine branch
Valine carbon proceeds through propionyl-CoA toward succinyl-CoA.
Reaction steps
1TransaminationBranched-chain amino acids + 2-Oxoglutarate ⇌ Branched-chain alpha-keto acids + Glutamate
BCAT transfers amino groups to alpha-ketoglutarate, forming glutamate and the corresponding keto acids.
REACTION · PER TURN + reversibly yields +
- Enzyme
- EC 2.6.1.42 ↗
- Cofactors
- No metal cofactor listed.
- Reversibility
- Reversible, operating near equilibrium in cells.
- Runs per branched-chain amino acids
- Once
- Stage
- Shared first steps
MECHANISM & CONTEXT
BCAT1 acts mainly in cytosol and BCAT2 in mitochondria. This grouped reaction represents three alternative substrates, not one reaction in which all three amino acids are consumed together.
Evidence for this step: Branched-chain amino acid catabolism (R-HSA-70895)
2Oxidative decarboxylationBranched-chain alpha-keto acids + Coenzyme A + NAD+ → Branched-chain acyl-CoA intermediates + Carbon dioxide + NADH
The BCKDH complex converts the branched-chain keto acids to acyl-CoA products and NADH.
REACTION · PER TURN + + yields + +
- Enzyme
- EC 1.2.4.4 ↗
- Cofactors
- No metal cofactor listed.
- Reversibility
- Irreversible under cellular conditions. This is a control point.
- Runs per branched-chain amino acids
- Once
- Stage
- Shared first steps
MECHANISM & CONTEXT
This shared step is irreversible and regulated by phosphorylation. The branched acyl-CoA products diverge into different pathways.
Evidence for this step: Branched-chain amino acid catabolism (R-HSA-70895)
3Leucine oxidation to isovaleryl-CoABranched-chain acyl-CoA intermediates + FAD → Isovaleryl-CoA + FADH2
The leucine-derived acyl-CoA proceeds through isovaleryl-CoA and its oxidation products.
REACTION · PER TURN + yields +
- Enzyme
- EC 1.3.8.4 ↗
- Cofactors
- No metal cofactor listed.
- Reversibility
- Irreversible under cellular conditions. This is a control point.
- Runs per branched-chain amino acids
- Once
- Stage
- Leucine branch
MECHANISM & CONTEXT
The early leucine-specific sequence includes isovaleryl-CoA dehydrogenase, 3-methylcrotonyl-CoA carboxylase, and additional rearrangements.
Evidence for this step: Branched-chain amino acid catabolism (R-HSA-70895)
4Leucine carbon to ketone products3-Methylcrotonyl-CoA → Acetoacetate + Acetyl-CoA
The leucine branch ultimately yields acetoacetate and acetyl-CoA.
REACTION · PER TURNyields +
- Enzyme
- EC 4.1.3.4 ↗
- Cofactors
- No metal cofactor listed.
- Reversibility
- Irreversible under cellular conditions. This is a control point.
- Runs per branched-chain amino acids
- Once
- Stage
- Leucine branch
MECHANISM & CONTEXT
These products are ketogenic: they can support ketone-body or acetyl-CoA metabolism but cannot provide net glucose carbon in humans.
Evidence for this step: Branched-chain amino acid catabolism (R-HSA-70895)
5Isoleucine carbon to acetyl-CoA and propionyl-CoABranched-chain acyl-CoA intermediates + Coenzyme A → Acetyl-CoA + Propionyl-CoA
The isoleucine branch yields both acetyl-CoA and propionyl-CoA.
REACTION · PER TURN + yields +
- Enzyme
- EC 2.3.1.16 ↗
- Cofactors
- No metal cofactor listed.
- Reversibility
- Irreversible under cellular conditions. This is a control point.
- Runs per branched-chain amino acids
- Once
- Stage
- Isoleucine branch
MECHANISM & CONTEXT
The products make isoleucine both ketogenic and glucogenic; propionyl-CoA is converted through methylmalonyl-CoA to succinyl-CoA.
Evidence for this step: Branched-chain amino acid catabolism (R-HSA-70895)
6Valine carbon to propionyl-CoABranched-chain acyl-CoA intermediates → Propionyl-CoA
The valine branch proceeds to propionyl-CoA and then succinyl-CoA.
REACTION · PER TURNyields
- Enzyme
- EC 1.2.4.4 ↗
- Cofactors
- No metal cofactor listed.
- Reversibility
- Irreversible under cellular conditions. This is a control point.
- Runs per branched-chain amino acids
- Once
- Stage
- Valine branch
MECHANISM & CONTEXT
The intervening pathway includes several valine-specific enzymes; this summary step keeps the initial map focused on the point of entry to central metabolism.
Evidence for this step: Branched-chain amino acid catabolism (R-HSA-70895)
7Propionyl-CoA entry as succinyl-CoAPropionyl-CoA → Succinyl-CoA
After carboxylation and epimerization, methylmalonyl-CoA mutase forms succinyl-CoA.
REACTION · PER TURNyields
- Enzyme
- EC 5.4.99.2 ↗
- Cofactors
- No metal cofactor listed.
- Reversibility
- Irreversible under cellular conditions. This is a control point.
- Runs per branched-chain amino acids
- Once
- Stage
- Valine branch
MECHANISM & CONTEXT
The grouped upstream steps require biotin and vitamin B12-dependent chemistry. Succinyl-CoA enters the TCA cycle and can contribute to gluconeogenesis.
Evidence for this step: Branched-chain amino acid catabolism (R-HSA-70895)
Research sources, claims, and curation
Branched-chain amino acid catabolism (R-HSA-70895)
Reactome · Homo sapiens · Reviewed Reactome human pathway used for reaction sequence and context.
Claims
Leucine, isoleucine, and valine share transamination and oxidative decarboxylation steps, then diverge. Leucine is ketogenic; isoleucine is both ketogenic and glucogenic; valine is glucogenic. Their carbon enters metabolism as acetyl-CoA, acetoacetate, or succinyl-CoA.
Curation notes
- The initial collection's broad amino-acid-catabolism slot is represented by the reviewed branched-chain amino-acid pathway; it is not a complete map of all 20 amino acids.
- Grouped branch reactions stand for several individual transformations; no overall net yield is calculated.
- The ketogenic/glucogenic classification describes carbon endpoints and does not imply that amino acids are used only for fuel.