5- Adenosyl methionine uroporphyrinogen

Fig. 10. a M-1, SAM or S-adenosyl methionine uroporphyrinogen III methyl transferase (SUMT), SAM b cbiF, SAM c [l,5]sigmatropic methyl shift... 

P. are the intermediates occurring after uroporphyrinogen in the biosynthetic pathway to vitamin B,2. The most important of the as yet discovered P. is P. 2 which can be transformed into other porphinoid natural products such as siroheme and factor F 430. P. 2 is derived from uroporphyrinogen III via P. I, a tetrahydro form of factor I, by methylation with 5-adenosyl-methionine (SAM). Methylation to P. 3A and further reaction steps finally lead to vitamin B,2, with the car-... 

Methylation of uroporphyrinogen III (14) by means of 5-adenosyl-methionine (SAM) forms directly the reduced form of (65). Factor I is obtained as an artefact by oxidation during the isolation procedure. Typically as for most of the methylation reactions with SAM the methyl group is transferred with inversion of configuration. Biosynthesis of heme (1) and chlorophyll a (2) as well as other chlorophyll derivatives branches out on the protoporphyrin IX (26) stage. 

The uroporphyrinogen III methylase (Ml) from Escherichia coli, which was over expressed and therefore available in sufficient amounts, methylates uroporphyrinogen III (14) in the presence of 5-adenosyl methionine (SAM) on the biosynthetic pathway to siroheme (110) (76). 

Methylation of the hexahydroporphyrinoid uroporphyrinogen III (14) with methyl groups from 5-adenosyl-methionine (SAM) at pyrrole ring... 

LEUSTEK, T SMITH, M MURILLO, M., SINGH, D. P., SMITH, A. G., WOODCOCK, S. C AW AN, S. J., WARREN, M. J., Siroheme biosynthesis in higher plants - Analysis of an S- adenosyl-L-methionine-dependent uroporphyrinogen III methyltransferase from Arabidopsis thaliana., J. Biol. Chem., 1997,272,2744-2752. 

Vevodova J, Graham RM, Raux E, Schubert HL, Roper Dl, Brindley AA, et al. Structure/function studies on a S-adenosyl-L-methionine-dependent uroporphyrinogen 111 C methyltransferase (SUMT), a key regulatory enzyme of tetrapyrrole biosynthesis. J. Mol. Biol. 2004 344 419-433. 

From feeding experiments with isotopically labelled 5-aminolevu-linic acid (18) and methionine (142) it became clear that the carbon skeleton of the naturally occurring highly saturated porphyrins are formed from uroporphyrinogen III (14) and that the additional methyl groups are transferred from 5-adenosyl methione (77, 72). 

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