Showing papers on "Protoporphyrins published in 1986"

Metal protoporphyrins in the control of tryptophan metabolism

Abstract: Method of controlling the rate of tryptophan metabolism in the liver of humans by parenteral administration of tin or chromium protoporphyrin to increase the rate, and the administration of cobalt protoporphyrin to decrease the rate.

N-alkylation of exogenous haem analogues caused by drugs in isolated hepatocytes. Structural isomerism and chirality of the resulting porphyrins.

Abstract: Isolated rat hepatocytes incubated with two suicide substrates of cytochrome P-450, 2-allyl-2-isopropylacetamide and 3,5-diethoxycarbonyl-4-ethyl-1,4-dihydro-2,6-dimethylpyridine(4-ethyl-DD C), convert exogenous mesohaem and deuterohaem into N-alkylated mesoporphyrins and deuteroporphyrins respectively. The N-alkylated mesoporphyrins can be separated by h.p.l.c. from the corresponding N-alkylated protoporphyrins originating from endogenous haem; in this way the contribution of both endogenous and exogenous pools of haem can be studied in the same experiment. N-Alkylated mesoporphyrin exhibits chiral properties, and its isomeric composition and/or amount are dependent on the particular cytochrome P-450 enzyme predominating in the cell. These findings provide additional and more direct evidence that exchangeable haem is taken up by cytochrome P-450 before being N-alkylated.

Isomeric composition of N-alkylated protoporphyrins produced by substituted dihydropyridines in vivo and in vitro.

Abstract: Substituted dihydropyridines, like DDC and its 4-ethyl analogue (4-ethyl-DDC)* give rise to N-alkylated porphyrins when given to rats and mice in vivo, by donating their intact 4-alkyl group to one of the pyrrole nitrogens of haem in hepatic cytochrome P-450 (De Matteis et al., 1981; Ortiz de Montellano et al., 1981; Tephly et al., 1981). Because of the asymmetrical arrangement of the two vinyl and propionate side chains in protoporphyrin IX, four structural isomers of N-monoalkylated protoporphyrins are possible, according to which of the four pyrrole nitrogens has been substituted. In a previous paper (De Matteis et al., 1983) we have provided evidence that the isomeric composition of the N-ethyl protoporphyrin produced in vivo by treatment with 4-ethyl-DDC depends on the particular cytochrome P-450 which predominates at the time of treatment, suggesting a role for the apo-cytochrome in directing alkylation preferentially on to one of the pyrrole nitrogens. In this present paper we wish to report additional findings in vivo which are compatible with this interpretation. Production of N-ethyl protoporphyrin is also found in vitro, when isolated microsomes are incubated with 4-ethyl-DDC in presence of NADPH and, although a change in isomeric profile is again found with microsomes containing different cytochrome P-450 enzymes, nevertheless the picture obtained with isolated membranes in vitro is different from that seen in the intact cells in vivo.