Mechanism and stereochemistry of vinyl-group formation in haem biosynthesis.
5-Aminolaevulinate containing tritium at C-3 and C-5 was converted into haem using a preparation of anaemic chicken blood. The biosynthetic haem was degraded to ethylmethyl maleimide and haematinic acid which had relative tritium radioactivity of 0.58 and 1.0 respectively. These results indicated that in the formation of the vinyl group of haem only one of the hydrogen atoms from the beta-positions of two propionate side chains of coproporphyrinogne III was removed. Haem was also biosynthesised from [(3R)-3H1]2-oxoglutarate. The determination of relative radioactivity in ethylmethyl maleimide and haematinic acid endorsed the above conclusion and further indicated that the pro-R hydrogen atoms located at the beta-positions of the propionate side chains are retained in haem biosynthesis. In order to explore the status of hydrogen atoms located at the alpha-positions of propionate side chains haem was biosynthesised using [2RS)-3H2]succinate, [(2R)-3H1]succinate and [(2S)-3H1]succinate. Degradation of the three samples of haem into ethylmethyl maleimide and haematinic acid showed that both the vinyl groups of haem are formed through the loss of pro-S hydrogen atoms located at the beta-positions of the propionic acid side chains of coproporphyrinogen III. The results further showed that the hydrogen atoms located at the alpha-positions of the side chains are not involved in the biosynthesis of haem. Various mechanisms for the formation of vinyl groups in the biosynthesis are discussed.
D000622:Aminolevulinic Acid / Q000378:metabolism; D000740:Anemia / Q000378:metabolism*; D000818:Animals; D002645:Chickens; D006418:Heme / Q000096:biosynthesis*; D007656:Ketoglutaric Acids / Q000378:metabolism; D013237:Stereoisomerism; D013386:Succinates / Q000378:metabolism; D014753:Vinyl Compounds
D007656:Ketoglutaric Acids; D013386:Succinates; D014753:Vinyl Compounds; D006418:Heme; D000622:Aminolevulinic Acid