Current Drug Metabolism - Volume 3, Issue 2, 2002

Tetrahydrobiopterin plays an essential role in nitric oxide synthase catalysis, not only as an allosteric modulator but also as a cofactor involved in electron flow through the enzyme. In absence of tetrahydrobiopterin, all isoforms of nitric oxide synthases are virtually inactive. The present review focusses on attempts to inhibit nitric oxide synthase by biopterin analogues, and what is known about the pharmacological effects of the Read More

Tetrahydrobiopterin (BH4) deficiencies are disorders affecting phenylalanine metabolism in liver and neurotransmitters biosynthesis in brain. BH4 is the essential cofactor in the enzymatic hydroxylation of 3 aromatic amino acids (phenylalanine, tyrosine, and tryptophan). BH4 is synthesized from guanosine triphosphate (GTP) catalyzed by GTP cyclohydrolase I (GTPCH), 6-pyruvoyl-tetrahydropterin synthase, and sepiapterin reducta Read More

Ever since the discovery that (6R)-5,6,7,8-tetrahydro-L-biopterin (BH4) is a cofactor of NOS, its function has been the object of intense research and occasional controversy. Only in the last couple of years a consensus has been reached on what constitutes the main role of BH4 in NO synthesis. In this review we aim to provide an outline of the various ways in which BH4 affects NOS catalysis. First we give a brief general description Read More

Tetrahydrobiopterin (H4-biopterin) is an essential cofactor of a set of enzymes that are of central metabolic importance, i.e. the hydroxylases of the three aromatic amino acids phenylalanine, tyrosine, and tryptophan, of ether lipid oxidase, and of the three nitric oxide synthase (NOS) isoenzymes. As a consequence, H4-biopterin plays a key role in a vast number of biological processes and pathological states associated Read More

Increased amounts of neopterin are produced by human monocytes / macrophages upon stimulation with the cytokine interferon-γ. Therefore, measurement of neopterin concentrations in body fluids like serum, cerebrospinal fluid or urine provides information about activation of T helper cell 1 derived cellular immune activation. Increased neopterin production is found in infections by viruses including human immunodefici Read More

Transplantation has become an established and successful therapy. Rejections and infections are the principal immune-related complications in the post-transplant course. A reliable and early diagnosis is necessary to prevent graft failure and patient morbidity. Despite the immunologic nature of these complications the diagnostic procedures still rely on functional tests and organ biopsies. Non-invasive monitoring remains to be on Read More

Pteridine derivatives which have a widespread occurrence in nature have been investigated upon their interactions with free radicals and free radical mediated reactions utilizing a number of different experimental systems. Searching for biological functions, which are still unknown for the majority of pteridine compounds, the effect of pteridines in systems like luminol-induced chemiluminescence, enzyme activity, DNA phot Read More

Folates are important cofactors in the transfer and utilization of one-carbon-groups and play a key role in the remethylation of methionine thus providing essential methyl groups for numerous biological reactions. Furthermore, folates donate one-carbon units in the process of DNA-biosynthesis with implications for the regulation of gene expression, transcription, chromatine structure, genomic repair and genomic st Read More

Tetrahydrofolate is an essential cofactor for the conversion of homocysteine to methionine, and hyperhomocysteinemia is considered as a risk factor for cardiovascular and cerebrovascular diseases. In subjects with hyperhomocysteinemia usually an inverse relationship exists to folic acid levels, and supplementation with folic acid is able to lower homocysteine concentrations. The pathogenesis of most if not all diseases wh Read More