Biosynthesis of 5-aminolevulinic acid and heme from 4,5-dioxovalerate in the rat.
We previously demonstrated an alternate pathway for the biosynthesis of 5-aminolevulinic acid (ALA) in bovine liver mitochondria and of tetrapyrroles in suspensions of rat hepatocytes (1980. J. Biol. Chem. 255: 3742; 1981. Proc. Natl. Acad. Sci. USA. 78: 5335). This pathway involves a transamination reaction that incorporates the intact 5-carbon skeleton of 4,5-dioxovaleric acid (DOVA) into ALA. We investigated this alternate pathway in vivo by the intraperitoneal injection of DOVA into rats. Incorporation of DOVA and [5-14C]DOVA into urinary ALA and hepatic and erythroid heme was quantified and compared with the incorporation of [4-14C]ALA and [2-14C]glycine into heme. Within 3 h of injection of 175 mumol of DOVA, urinary ALA excretion increased 2.4-fold over controls. After injection of [5-14C]DOVA, 0.11% of the radioactivity was recovered as urinary ALA, which quantitatively accounted for the 2.4-fold increase in ALA excretion. After the injection 175 mumol of [5-14C]DOVA, 0.14% of the radioactivity was recovered after 3 h as hepatic heme. The injection of 1.75 mmol of [2-14C]glycine or 175 mumol of [4-14C]ALA resulted in recovery of 0.2 and 3.4%, respectively, of the radioactivity as hepatic heme after 3 h. These doses of radiolabeled DOVA, glycine, and ALA were injected into rats with phenylhydrazine-induced anemia. Recovery of radioactivity after 3 h as splenic (erythroid) heme was 0.35% for DOVA, 0.072% for glycine, and 0.25% for ALA. These studies establish that the intact 5-carbon skeleton of DOVA can be incorporated into ALA and heme in vivo.
D000622:Aminolevulinic Acid / Q000378:metabolism / Q000652:urine*; D000743:Anemia, Hemolytic / Q000139:chemically induced / Q000378:metabolism; D000818:Animals; D005998:Glycine / Q000378:metabolism; D006418:Heme / Q000096:biosynthesis*; D007982:Levulinic Acids / Q000652:urine*; D008099:Liver / Q000378:metabolism; D008297:Male; D010659:Phenylhydrazines; D051381:Rats; D011919:Rats, Inbred Strains; D014631:Valerates / Q000378:metabolism*
D007982:Levulinic Acids; D010659:Phenylhydrazines; D014631:Valerates; C030299:phenylhydrazine; D006418:Heme; C007509:4,5-dioxovaleric acid; D000622:Aminolevulinic Acid; D005998:Glycine