Reactome | ALAS condenses SUCC-CoA and Gly to form dALA

ALAS condenses SUCC-CoA and Gly to form dALA

Stable Identifier

R-HSA-189442

Type

Reaction [transition]

Species

Homo sapiens

Compartment

mitochondrial matrix

Synonyms

glycine + H(+) + succinyl-CoA => 5-aminolevulinate + CO2 + CoA, Succinyl CoA and glycine condense to form 5-aminolevulinate (ALA)

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

ALAS condenses SUCC-CoA and Gly to form dALA

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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
1939222	Biosynthesis of delta-aminolevulinic acid and the regulation of heme formation by immature erythroid cells in man Cox, TM, Smith, SJ, Gardner, LC	J Biol Chem	1991
16121195	Crystal structure of 5-aminolevulinate synthase, the first enzyme of heme biosynthesis, and its link to XLSA in humans Heinz, DW, Jahn, D, Schubert, WD, van den Heuvel, J, Schulze, JO, Astner, I	EMBO J	2005