ALAS condenses SUCC-CoA and Gly to form dALA

Stable Identifier
R-HSA-189442
Type
Reaction [transition]
Species
Homo sapiens
Compartment
Synonyms
Succinyl CoA and glycine condense to form 5-aminolevulinate (ALA)
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The committed step for porphyrin synthesis is the formation of 5-aminolevulinate (ALA) by condensation of glycine (from the general amino acid pool) and succinyl-CoA (from the TCA cycle), in the mitochondrial matrix. The reaction is catalyzed by two different ALA synthases, one expressed ubiquitously (ALAS1) and the other only expressed in erythroid precursors (ALAS2). Both enzymes are expressed as homodimers and require pyridoxal 5-phosphate as a cofactor.
No disease-causing mutations of ALAS1 have been recognised in humans. Mutations in ALAS2 cause X-linked sideroblastic anaemia (XLSA), characterised by a microcytic hypochromic anaemia.

Literature References
PubMed ID Title Journal Year
16121195 Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans

Astner, I, Schulze, JO, van den Heuvel, J, Jahn, D, Schubert, WD, Heinz, DW

EMBO J 2005
1939222 Biosynthesis of delta-aminolevulinic acid and the regulation of heme formation by immature erythroid cells in man

Gardner, LC, Smith, SJ, Cox, TM

J Biol Chem 1991
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
5-aminolevulinate synthase activity of ALAS1,2 [mitochondrial matrix]
Physical Entity
Activity
This event is regulated
Orthologous Events
Cross References
Rhea
Authored
Reviewed
Created