The interplay between basicity, conformation, and enzymatic reduction in biliverdins.

BARI, SARA E. ; FRYDMAN, ROSALÍA BRYKS DE; GROSMAN, CLAUDIO; FRYDMAN, JAIME BENJAMÍN

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 1992 vol. 188 p. 48 - 56

0006-291X

Biliverdins with extended conformations are reduced by biliverdin reductase(BvR) at higher rates than biliverdins with helical conformations. To find outthe molecular basis for this important feature of BvR mechanism, helical andextended biliverdins were titrated for their acid-base equilibria in a proticsolvent (methanol). It was found that the basicity of biliverdins increases withthe stretching of the conformation. Biliverdin IX gamma (all-syn) has a pKa =3.6; 5,10,15-syn,syn,anti-biliverdin has a pKa = 3.7; 5,10,15-syn,anti,syn-biliverdin has a pKa = 6.1;5,10,15-syn,anti,anti-biliverdin has a pKa = 6.4; and 5,10,15-all-anti-biliverdin has a pKa = 7.9. The increase in basicity withprogressive stretching of conformations closely parallels the increase in thereduction rates by BvR. A biliverdin constrained by a four carbon chain to ahelical conformation and which is a very weak base (pKa = 0.4) is not reduced byBvR. Nucleophilic additions of 2-mercaptoethanol at the C10 in biliverdinsclosely parallel their basicities, as can be expected if the formation of apositive mesomeric species at C10 is linked to the basicity (i.e., the ease ofprotonation) of the N23 on the pyrrolenine ring.