Conversion of 5-aminolaevulinate into haem by liver homogenates. Comparison of rat and chick embryo.
1. We have studied the kinetics of the conversion of 5-aminolaevulinate into haem and haem precursors in homogenates of livers of rats and chick embryos. Homogenates of fresh liver from both species efficiently convert 5-aminolaevulinate into haem. After frozen storage for 1 year, homogenates of rat, but not chick, liver have decreased rates of formation of haem with accumulation of more protoporphyrin. The rate of haem formation after storage is restored by addition of Fe2+ and menadione. 2. At all initial concentrations of 5-aminolaevulinate tested (2 microM-1 mM), homogenates of rat liver accumulate less protoporphyrin than haem. In contrast, homogenates of chick embryo liver accumulate more protoporphyrin than haem at concentration of 5-aminolaevulinate greater than 10 microM. Conversion of protoporphyrin into haem by homogenates of fresh or frozen chick embryo liver is not increased by addition of Fe2+. 3. Homogenates of liver from both species accumulate porphobilinogen; the kinetic parameters for this process reflect those of 5-aminolaevulinate dehydratase. 4. The results show that the rate-limiting enzyme for the hepatic conversion of 5-aminolaevulinate into protoporphyrin is porphobilinogen deaminase. In addition, chick liver, compared with rat liver, has only about one-fifth the activity of ferrochelatase, the final enzyme of the haem biosynthetic pathway, which inserts Fe2+ into protoporphyrin to form haem. 5. Comparison of these results with previous studies indicates that the homogenate system described here provides physiologically and clinically relevant information for study of hepatic haem synthesis and its control.
D000622:Aminolevulinic Acid / Q000378:metabolism*; D000818:Animals; D002642:Chick Embryo; D005296:Ferrous Compounds / Q000494:pharmacology; D006418:Heme / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007700:Kinetics; D007982:Levulinic Acids / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D008297:Male; D011162:Porphobilinogen / Q000096:biosynthesis; D011166:Porphyrins / Q000096:biosynthesis; D011524:Protoporphyrins / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains
D005296:Ferrous Compounds; D007982:Levulinic Acids; D011166:Porphyrins; D011524:Protoporphyrins; C020748:ferrous sulfate; D006418:Heme; D011162:Porphobilinogen; D000622:Aminolevulinic Acid