Vol.11, No 2, 2004 pp. 49 - 54
UC 577+61

BIOCHEMICAL FUNCTIONS AND CLINICAL IMPORTANCE
OF UNCONJUGATED PTERIDINES
Gordana Bjelaković1, Tatjana Jevtović-Stoimenov1, Bojko Bjelaković2, Ivana Stojanović1
1Institute of Biochemistry, Faculty of Medicine, University of Niš
2Clinic of Pediatrics, Faculty of Medicine, University of Niš, Serbia and Montenegro

Summary. Tetrahydrobiopterine (BH4) and its relatives are classified as unconjugated pteridines or pterins  distinguishing them from the folates. BH4 is not a vitamin for mammals, since they can synthesize it. GTP is the major precursor of atoms in the pterin nucleus. The initial step in this pathway is conversion of GTP to D-erythro-7, 8-dihydroneopterin triphosphate, a reaction catalyzed by the enzyme GTP-cyclohydrolase I (EC 3.5.4.16; GTP-CH). There are many important metabolic functions of BH4: it is a crucial cofactor in hydroxylation reactions of phenylalanine, tyrosine and tryptophane. The finding of BH4 participation in monoaminergic neurotransmitter metabolism regulation contributed to the knowledge of atipic neurological symptoms in some kinds of "phenylketonuric" children. As a cofactor of nitric oxide syntheses BH4 is a crucial metabolite involved in physiological function of cardiovascular system. The literature data confirm that the BH4 depletion is crucial in the control of both NO and superoxide generation (H2O2), synthesized by endothelial  NOS isoforms, and consequently the formation of cell toxic peroxynitrite (ONOO -). Relationships between biosynthesis of BH4 and guanine nucleotide regulatory proteins (G proteins) or GTP-binding proteins taking part in protein synthesis has to be explained. The idea that all oxidases using molecular oxygen and producing H2O2 need BH4  appears rather relevant and it may explain more successfully the polyamine oxidase activity (PAO) in the regulation of polyamine metabolism.
Key words: Unconjugated pteridines, BH4, metabolic function, GTP binding proteins, polyamines, clinical disorders

BIOHEMIJSKE FUNKCIJE I KLINIČKI ZNAČAJ NEKONJUGOVANIH PTERIDINA
Kratak sadržaj: Tetrahidrobiopterin (BH4) i njegovi metaboliti klasifikuju se kao nekonjugovani pteridini ili pterini za razliku od folne kiseline i njenih derivata koji čine grupu konjugovanih pteridina. BH4 nije vitamin za sisare, koji mogu da ga sintetišu. GTP je glavni prekursor atoma u molekulu pterina. Glavni stupanj na putu prevodjenja GTP-a u D-erithro-7, 8-dihidroneopterin trifosfat, je reakcija katalizovana od strane enzima GTP-ciklohidrolaze I (EC 3.5.4.16; GTP-CH). Postoje brojne metabolički značajne funkcije BH4: on je ključni kofaktor u reakcijama hidroksilacije fenilalanina, tirozina i triptofana. Upoznavanje učešća BH4 u regulaciji metabolizma monoaminergičnih neurotransmitera dovelo je do boljeg upoznavanja atipičnih neuroloških simptoma u nekim oblicima "fenilketonurične" dece. Kao kofaktor azot oksid sintaze BH4 je ključni metabolit zar fiziološke funkcije kardiovaskularnog sistema. Podaci iz literature ukazuju da deplecija BH4 je ključna u kontroli produkcije NO i vodonik peroksida (H2O2) pomoću endotelijalne NOS iziforme, i posledičnog formiranja celularno toksičnog peroxinitrita (ONOO -). Medjuodnosi u biosintezi BH4 i guanin nukleotid regulatornih proteina (G proteina) ili GTP-vezujućih proteina koji su uključeni u proces biosinteze proteina potrebno je tek razjasniti. Ideja da sve oksidaze koje koriste molekularni kiseonik i produkuju H2O2 zahtevaju BH4 jeste veoma interesantna. Ova konstatacija može doprineti boljem upoznavanju aktivnosti poliamin oksidaze (PAO) u regulaciji metabolizma poliamina.
Ključne reči: Nekonjugovani pteridini, BH4, GTP-vezujući proteini, poliamini, klinički poremećaji