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
