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New aspects in biopterin biosynthesis in man
Author(s) -
Häusermann M.,
Ghisla S.,
Niederwieser A.,
Curtius H.-Ch.
Publication year - 1981
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(81)80383-3
Subject(s) - curtius rearrangement , chemistry , library science , stereochemistry , computer science
Tetrahydrobiopterin is synthesized from guanosine triphosphate (GTP)in several enzymatic steps [ 1,2]. Details of the pathway of the biopterin biosynthesis in mammals are still unresolved [3]. In rat and human brain the rate-limiting enzyme was GTP cyclohydrolase [2], followed by D-erythro-7,8-dihydroneopterin triphosphate synthetase. D-Erythro-7,8-dihydroneopterin triphosphate was directly converted to 'quinonoid' dihydrobiopterin by an enzyme not requiring pyridine nucleotides or other cofactors for catalytic activity [2]. This is in contrast to other results [1 ] demonstrating that the conversion of D-erythro-7,8dihydroneopterin triphosphate to L-erythro-dihydrobiopterin required 3 distinct protein fractions. A Mg2+-dependent enzyme (A2) catalyzed the conversion of D-erythro-7,8-dihydroneopterin triphosphate to an intermediate X of unknown structure proposed to be 6(1 ',2'-dioxopropyl)-7,8-dihydropterin which could be degraded to pterin and pyruvic acid [1]. A heat labile and NADPH-dependent enzyme (A1) converted X to sepiapterin. We reported in [4] that 3'-hydroxysepiapterin is excreted in small amounts in the urine of healthy individuals but it is markedly increased in patients with dihydrobiopterin-deficiency. In connection with our studies of atypical phenylketonuria, it was of interest to investigate the biopterin biosynthesis in man. These data indicate that, indeed, also in human kidney and liver, biopterin synthesis might proceed via compound X and sepiapterin.