Search PubMed⌕ Search

PubMed · 6458763

Pteroylpolyglutamates.

Abstract

Reduced derivatives of the vitamin pteroylglutamic acid (folic acid) are essential coenzymes for the biosynthesis of purine nucleotides, methionine, thymidylate and for many other enzyme catalyzed reactions involving the transfer, oxidation and reduction of single carbon units. Pteroylglutamic acid is found in tissues in the form of poly-gamma-glutamyl derivatives of varying chain length. The present review covers the detection, distribution, synthesis, degradation, coenzyme function and inhibitory activities of pteroyl-gamma-glutamates. The biosynthesis and inhibitory activities of poly-gamma-glutamyl derivatives of methotrexate, an analog of pteroylglutamic acid having antitumor activity, are also considered. An hypothesis on the coenzymatic role of pteroylpoly-gamma-glutamates in the coordination of sequential enzymatic steps in the metabolism of single carbon units is presented.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

R L Kisliuk. 1981-09-25. Pteroylpolyglutamates.. https://doi.org/10.1007/bf00232583

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Design, synthesis, and biological evaluation of phosphinopeptides against Trypanosoma cruzi targeting trypanothione biosynthesis.

As a part of our project aimed at the search for new safe chemotherapeutic and chemoprophylactic agents against American trypanosomiasis (Chagas's disease), a series of phosphinopeptides structurally related to glutathione was designed, synthesized, and evaluated as antiproliferative agents against the parasite responsible for this disease, the hemoflagellated protozoan Trypanosoma cruzi. The rationale for the synthesis of these compounds was supported on the basis that the presence of the phosphinic acid moiety would mimic the tetrahedral transition state of trypanothione synthase (TryS), a typical C:N ligase, and the molecular target of these drugs. Of the designed compounds, 53 and 54 were potent growth inhibitors against the clinically more relevant form of T. cruzi (amastigotes) growing in myoblasts. The efficacy for these drugs was comparable to that exhibited by the well-known antiparasitic agent WC-9. The simple phosphinopeptide structure found as a pharmacophore in the present study constitutes a starting point for the development of straightforward optimized drugs.

Amide Synthases↗

Comparative genomics of NAD biosynthesis in cyanobacteria.

Biosynthesis of NAD(P) cofactors is of special importance for cyanobacteria due to their role in photosynthesis and respiration. Despite significant progress in understanding NAD(P) biosynthetic machinery in some model organisms, relatively little is known about its implementation in cyanobacteria. We addressed this problem by a combination of comparative genome analysis with verification experiments in the model system of Synechocystis sp. strain PCC 6803. A detailed reconstruction of the NAD(P) metabolic subsystem using the SEED genomic platform (http://theseed.uchicago.edu/FIG/index.cgi) helped us accurately annotate respective genes in the entire set of 13 cyanobacterial species with completely sequenced genomes available at the time. Comparative analysis of operational variants implemented in this divergent group allowed us to elucidate both conserved (de novo and universal pathways) and variable (recycling and salvage pathways) aspects of this subsystem. Focused genetic and biochemical experiments confirmed several conjectures about the key aspects of this subsystem. (i) The product of the slr1691 gene, a homolog of Escherichia coli gene nadE containing an additional nitrilase-like N-terminal domain, is a NAD synthetase capable of utilizing glutamine as an amide donor in vitro. (ii) The product of the sll1916 gene, a homolog of E. coli gene nadD, is a nicotinic acid mononucleotide-preferring adenylyltransferase. This gene is essential for survival and cannot be compensated for by an alternative nicotinamide mononucleotide (NMN)-preferring adenylyltransferase (slr0787 gene). (iii) The product of the slr0788 gene is a nicotinamide-preferring phosphoribosyltransferase involved in the first step of the two-step non-deamidating utilization of nicotinamide (NMN shunt). (iv) The physiological role of this pathway encoded by a conserved gene cluster, slr0787-slr0788, is likely in the recycling of endogenously generated nicotinamide, as supported by the inability of this organism to utilize exogenously provided niacin. Positional clustering and the co-occurrence profile of the respective genes across a diverse collection of cellular organisms provide evidence of horizontal transfer events in the evolutionary history of this pathway.

Amide Synthases↗