PT  - JOURNAL ARTICLE
AU  - Bennett, B M
AU  - Kobus, S M
AU  - Brien, J F
AU  - Nakatsu, K
AU  - Marks, G S
TI  - Requirement for reduced, unliganded hemoprotein for the hemoglobin- and myoglobin-mediated biotransformation of glyceryl trinitrate.
DP  - 1986 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 629--635
VI  - 237
IP  - 2
4099  - http://jpet.aspetjournals.org/content/237/2/629.short
4100  - http://jpet.aspetjournals.org/content/237/2/629.full
SO  - J Pharmacol Exp Ther1986 May 01; 237
AB  - The biotransformation of glyceryl trinitrate (GTN) by hemoglobin (Hb) and myoglobin (Mb) was assessed using solutions of various forms of the hemoproteins, viz., the oxy-, deoxy-, carbonmonoxy- and met-forms. After incubation with these, GTN loss was observed only with the deoxy-forms of Hb and Mb. The stoichiometry and products of [14C]GTN biotransformation by deoxy-Hb and deoxy-Mb were determined by measuring the formation of [14C]glyceryl dinitrate [14C]GDN), met-Hb (or met-Mb) and inorganic nitrite anion. Biotransformation of GTN involved the oxidation of 2 mol of heme iron (II) per mol of GTN biotransformed to GDN and inorganic nitrite anion. In addition to the formation of GDN, 1 to 2.5% of the radioactivity could not be extracted from the incubation samples. The ratio of 1,2-GDN/1,3-GDN formed during incubation of deoxy-Hb with GTN was 11:1, which indicated a high degree of regioselectivity for the denitration of the nitrate ester group in position 1 or position 3 of GTN. The metabolite ratio obtained for deoxy-Mb incubation with GTN (1,2-GDN/1,3-GDN,3:1) was less than that for deoxy-Hb, which indicated less regioselectivity for the deoxy-Mb-mediated denitration reaction. This could reflect differences in the topography of the heme pocket of the two hemoproteins and steric differences in the GTN-hemoprotein interaction.