Puttur D. Prasad

Bio: Puttur D. Prasad is an academic researcher from Health Science University. The author has contributed to research in topics: Ascorbic acid & Amino acid. The author has an hindex of 5, co-authored 9 publications receiving 162 citations. Previous affiliations of Puttur D. Prasad include Texas Tech University Health Sciences Center.

Rapid Communication Up-regulation of the amino acid transporter ATB 0,+ (SLC6A14) in carcinoma of the cervix

Abstract: Objective. ATB 0,+ is an energy-coupled transporter for arginine and amino acid-based prodrugs. The objective of the study was to examine the

Species-specific Influence of Lithium on the Activity of SLC13A5 (NaCT): Lithium-induced Activation is Specific for the Transporter in Primates

Abstract: NaCT (SLC13A5) is a Na(+)-coupled transporter for Krebs cycle intermediates and is expressed predominantly in the liver. Human NaCT is relatively specific for citrate compared with other Krebs cycle intermediates. The transport activity of human NaCT is stimulated by Li(+), whereas that of rat NaCT is inhibited by Li(+). We studied the influence of Li(+) on NaCTs cloned from eight different species. Li(+) stimulated the activity of only NaCTs from primates (human, chimpanzee, and monkey); by contrast, NaCTs from nonprimate species (mouse, rat, dog, and zebrafish) were inhibited by Li(+). Caenorhabditis elegans NaCT was not affected by Li(+). With human NaCT, the Li(+)-induced increase in transport activity was associated with the conversion of the transporter from a low-affinity/high-capacity type to a high-affinity/low-capacity type. H(+) was able to substitute for Li(+) in eliciting the stimulatory effect. The amino acid Phe500 in human NaCT was critical for Li(+)/H(+)-induced stimulation. Mutation of this amino acid to tryptophan (F500W) markedly increased the basal transport activity of human NaCT in the absence of Li(+), but the ability of Li(+) to stimulate the transporter was almost completely lost with this mutant. Substitution of Phe500 with tryptophan in human NaCT converted the transporter from a low-affinity/high-capacity type to a high-affinity/low-capacity type, an effect similar to that of Li(+) on the wild-type NaCT. These studies show that Li(+)-induced activation of NaCT is specific for the transporter in primates and that the region surrounding Phe500 in primate NaCTs is important for the Li(+) effect.

Amino Acid Transporters in Cancer and Their Relevance to “Glutamine Addiction”: Novel Targets for the Design of a New Class of Anticancer Drugs

Abstract: Tumor cells have an increased demand for amino acids because of their rapid proliferation rate. In addition to their need in protein synthesis, several amino acids have other roles in supporting cancer growth. There are approximately two-dozen amino acid transporters in humans, and tumor cells must upregulate one or more of these transporters to satisfy their demand for amino acids. If the transporters that specifically serve this purpose in tumor cells are identified, they can be targeted for the development of a brand new class of anticancer drugs; the logical basis of such a strategy would be to starve the tumor cells of an important class of nutrients. To date, four amino acid transporters have been found to be expressed at high levels in cancer: SLC1A5, SLC7A5, SLC7A11, and SLC6A14. Their induction occurs in a cancer type-specific manner with a direct or indirect involvement of the oncogene c-Myc. Further, these transporters are functionally coupled, thus maximizing their ability to promote cancer growth and chemoresistance. Progress has been made in preclinical studies, exploiting these transporters as drug targets in cancer therapy. These transporters also show promise in development of new tumor-imaging probes and in tumor-specific delivery of appropriately designed chemotherapeutic agents.

Amino acids in cancer.

Abstract: Over 90 years ago, Otto Warburg's seminal discovery of aerobic glycolysis established metabolic reprogramming as one of the first distinguishing characteristics of cancer1. The field of cancer metabolism subsequently revealed additional metabolic alterations in cancer by focusing on central carbon metabolism, including the citric acid cycle and pentose phosphate pathway. Recent reports have, however, uncovered substantial non-carbon metabolism contributions to cancer cell viability and growth. Amino acids, nutrients vital to the survival of all cell types, experience reprogrammed metabolism in cancer. This review outlines the diverse roles of amino acids within the tumor and in the tumor microenvironment. Beyond their role in biosynthesis, they serve as energy sources and help maintain redox balance. In addition, amino acid derivatives contribute to epigenetic regulation and immune responses linked to tumorigenesis and metastasis. Furthermore, in discussing the transporters and transaminases that mediate amino acid uptake and synthesis, we identify potential metabolic liabilities as targets for therapeutic intervention.

Membrane transporters for the special amino acid glutamine: structure/function relationships and relevance to human health

Abstract: Glutamine together with glucose is essential for body’s homeostasis. It is the most abundant amino acid and is involved in many biosynthetic, regulatory and energy production processes. Several membrane transporters which differ in transport modes, ensure glutamine homeostasis by coordinating its absorption, reabsorption and delivery to tissues. These transporters belong to different protein families, are redundant and ubiquitous. Their classification, originally based on functional properties, has recently been associated with the SLC nomenclature. Function of glutamine transporters is studied in cells over-expressing the transporters or, more recently in proteoliposomes harboring the proteins extracted from animal tissues or over-expressed in microorganisms. The role of the glutamine transporters is linked to their transport modes and coupling with Na+ and H+. Most transporters share specificity for other neutral or cationic amino acids. Na+-dependent co-transporters efficiently accumulate glutamine while antiporters regulate the pools of glutamine and other amino acids. The most acknowledged glutamine transporters belong to the SLC1, 6, 7 and 38 families. The members involved in the homeostasis are the co-transporters B0AT1 and the SNAT members 1, 2, 3, 5 and 7; the antiporters ASCT2, LAT1 and 2. The last two are associated to the ancillary CD98 protein. Some information on regulation of the glutamine transporters exist, which, however, need to be deepened. No information at all is available on structures, besides some homology models obtained using similar bacterial transporters as templates. Some models of rat and human glutamine transporters highlight very similar structures between the orthologues. Moreover the presence of glycosylation and/or phosphorylation sites located at the extracellular or intracellular faces has been predicted. ASCT2 and LAT1 are over-expressed in several cancers, thus representing potential targets for pharmacological intervention.