Dependence of an alkyl glycol-ether monooxygenase activity upon tetrahydropterins

Kaufman, Seymour; Pollock, Robert; Summer, George K.; Das, Arun K.; Hajra, Amiya K.

doi:10.1016/0167-4838(90)90141-2

Cited by 40 publications

(43 citation statements)

References 36 publications

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“…Nonlinear regression analysis of the data shows that inhibition by DAHP is non-competitive with decreasing V max with increasing inhibitor concentration (K 0. 5 …”

Section: Gfrp-independent Inhibition Of Drosophila Gtpch Isoforms By mentioning

confidence: 99%

A typical N-terminal Extensions Confer Novel Regulatory Properties on GTP Cyclohydrolase Isoforms in Drosophila melanogaster

Funderburk¹,

Bowling²,

Xu³

et al. 2006

Journal of Biological Chemistry

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The cofactor tetrahydrobiopterin plays critical roles in the modulation of the signaling molecules dopamine, serotonin, and nitric oxide. Deficits in cofactor synthesis have been associated with several human hereditary diseases. Responsibility for the regulation of cofactor pools resides with the first enzyme in its biosynthetic pathway, GTP cyclohydrolase I. Because organisms must be able to rapidly respond to environmental and developmental cues to adjust output of these signaling molecules, complex regulatory mechanisms are vital for signal modulation. Mammalian GTP cyclohydrolase is subject to end-product inhibition via an associated regulatory protein and to positive regulation via phosphorylation, although target residues are unknown. GTP cyclohydrolase is composed of a highly conserved homodecameric catalytic core and non-conserved N-terminal domains proposed to be regulatory sites. We demonstrate for the first time in any organism that the N-terminal arms of the protein serve regulatory functions. We identify two different modes of regulation of the enzyme mediated through the N-terminal domains. The first is end-product feedback inhibition, catalytically similar to that of the mammalian enzyme, except that feedback inhibition by the cofactor requires sequences in the N-terminal arms rather than a separate regulatory protein. The second is a novel inhibitory interaction between the N-terminal arms and the active sites, which can be alleviated through the phosphorylation of serine residues within the N termini. Both mechanisms allow for acute and highly responsive regulation of cofactor production as required by downstream signaling pathways.

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“…Nonlinear regression analysis of the data shows that inhibition by DAHP is non-competitive with decreasing V max with increasing inhibitor concentration (K 0. 5 …”

Section: Gfrp-independent Inhibition Of Drosophila Gtpch Isoforms By mentioning

confidence: 99%

A typical N-terminal Extensions Confer Novel Regulatory Properties on GTP Cyclohydrolase Isoforms in Drosophila melanogaster

Funderburk¹,

Bowling²,

Xu³

et al. 2006

Journal of Biological Chemistry

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“…In addition, glyceryl ether cleavage in rat liver [3,4] and nitric oxide formation by conversion of arginine to citrulline require tetrahydrobiopterin [5 7].…”

Section: Introductionmentioning

confidence: 99%

The conformational flexibility of 5,6,7,8‐tetrahydrobiopterin and 5,6,7,8‐tetrahydroneopterin: a molecular dynamical simulation

1995

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“…oxygenase, which catalyses the oxidative cleavage of 1-O-alkyl glycerol to a long-chain aldehyde and glycerol [2], In activated macrophages, BH4 enhances the oxidative N-hydroxylation of L-arginine to nitric oxide (-N = O) and citrulline [3].…”

Section: Introductionmentioning

confidence: 99%

Purification and Characterization of 6-Pyruvoyl Tetrahydropterin Synthase from Human Pituitary Gland

Guzman

Redweik²,

Schoedon³

et al. 1992

Enzyme

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6-Pyruvoyl tetrahydropterin synthase, the enzyme that catalyses the conversion of 7,8-dihydroneopterin triphosphate to 6-pyruvoyl tetrahydropterin, was purified 3,330- fold from human pituitary gland with an overall recovery of 30%. The native enzyme has a molecular mass of 68 kD and consists of four identical subunits of 16.5 kD. The pH optimum of the enzyme in Tris/HCl buffer is 7.5. The enzyme is dependent on Mg^2+ and NADPH and has a Michaelis-Menten constant of 10 μM for its natural substrate, 7,8-dihydroneopterin triphosphate. The isoelectric point of the human enzyme is 4.3-4.6. The human pituitary gland enzyme is heat instable in contrast to the enzymes from human, rat and salmon liver, and Drosophila head. The amino acid composition showed remarkably high content of acidic amino acids Asp and Glu. The N-terminus was found to be blocked.

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Dependence of an alkyl glycol-ether monooxygenase activity upon tetrahydropterins

Cited by 40 publications

References 36 publications

A typical N-terminal Extensions Confer Novel Regulatory Properties on GTP Cyclohydrolase Isoforms in Drosophila melanogaster

A typical N-terminal Extensions Confer Novel Regulatory Properties on GTP Cyclohydrolase Isoforms in Drosophila melanogaster

The conformational flexibility of 5,6,7,8‐tetrahydrobiopterin and 5,6,7,8‐tetrahydroneopterin: a molecular dynamical simulation

Purification and Characterization of 6-Pyruvoyl Tetrahydropterin Synthase from Human Pituitary Gland

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