Publication Date:
1993-06-04
Description:
Guanosine triphosphate (GTP) cyclohydrolase I, the rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin (BH4), is subject to feedback inhibition by BH4, a cofactor for phenylalanine hydroxylase. Inhibition was found to depend specifically on BH4 and the presence of another protein (p35). The inhibition occurred through BH4-dependent complex formation between p35 protein and GTP cyclohydrolase I. Furthermore, the inhibition was specifically reversed by phenylalanine, and, in conjunction with p35, phenylalanine reduced the cooperativity of GTP cyclohydrolase I. These findings also provide a molecular basis for high plasma BH4 concentrations observed in patients with hyperphenylalaninemia caused by phenylalanine hydroxylase deficiency.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harada, T -- Kagamiyama, H -- Hatakeyama, K -- New York, N.Y. -- Science. 1993 Jun 4;260(5113):1507-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Osaka Medical College, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8502995" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Biological Factors/physiology
;
Biopterin/analogs & derivatives/physiology
;
Chromatography, Gel
;
Feedback
;
GTP Cyclohydrolase/antagonists & inhibitors/*metabolism
;
Humans
;
In Vitro Techniques
;
Liver/metabolism
;
Phenylalanine/physiology
;
Phenylalanine Hydroxylase/metabolism
;
Protein Binding
;
Rats
;
Recombinant Proteins/metabolism
;
Tissue Extracts
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
