Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was conducted in order to clarify the role of the glia in brain purine metabolism. This, in connection with the clarification of the etiology of the neurological manifestations associated with some of the inborn errors of purine metabolism in man. Purine nucleotide content, the capacity for de novo and salvage purine synthesis and the activity of several enzymes of purine nucleotide degradation, were assayed in primary cultures of rat astroglia in relation to culture age. The capacity of the intact cells to produce purine nucleotides de novo exhibited a marked decrease with the culture age, but the activity of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), catalyzing salvage nucleotide synthesis, increased. Aging was also associated with a marked increase in the activity of the degradation enzymes AMP deaminase, purine nucleoside phosphorylase (PNP) and guanine deaminase (guanase). The activity of adenosine deaminase and of AMP-5'-nucleotidase, increased markedly during the first 17 days in culture, but decreased thereafter. The results indicate that purine nucleotide metabolism in the cultured astroglia is changing with aging to allow the cells to maintain their nucleotide pool by reutilization of preformed hypoxanthine, rather than by de-novo production of new purines. Aging is also associated with increased capacity for operation of the adenine nucleotide cycle, contributing to the homeostasis of adenine nucleotides and to the energy charge of the cells. In principle, the age-related alterations in purine metabolism in the astroglia resemble those occurring in the maturating neurons, except for the capacity to produce purines de novo, which exhibited inverse trends in the two tissues. However, in comparison to the neurons, the cultured astroglia possess the capacity for a more intensive metabolism of purine nucleotides.
 ...
PMID:Developmental changes in purine nucleotide metabolism in cultured rat astroglia. 877 Jun 61

Many enzymes are involved in the biosynthesis, interconversion, and degradation of purine compounds. The exact function of these enzymes is still unknown, but they seem to play important roles other than in purine metabolism. To elucidate their functional roles, it is imperative to clarify their tissue distribution at the cellular or subcellular level. The present review summarizes the currently available information about their histochemical localization and proposed functions. In general, 5'-nucleotidase has been considered as a marker enzyme for the plasma membrane, and is considered to be a key enzyme in the generation of adenosine, a potential vasodilator. However, from its wide range of localization in tissues it is also considered to be related to the membrane movement of cells in the transitional epithelium, cellular motile response, transport process, cellular growth, synthesis of fibrous protein and calcification, lymphocyte activation, neurotransmission, and oxygen sensing mechanism. Adenosine deaminase (ADA) is present in all tissues in mammals. Although the main function of ADA is the development of the immune system in humans, it seems to be associated with the differentiation of epithelial cells and monocytes, neurotransmission, and maintenance of gestation. Purine nucleoside phosphorylase (PNP) is generally considered as a cytosolic enzyme, but recently, mitochondrial PNP, a different protein from cytosolic PNP, was reported. PNP is also widely expressed in human tissues. It is found in most tissues of the body, but the highest activity is in peripheral blood granulocyte and lymphoid tissues. It is also related to the development of T-cell immunity in humans as is ADA. Moreover, its contribution to centriole replication and/or regulation of microtubule assembly has been suggested. Immunohistochemical localization of xanthine oxidase has been reported in various tissues from various animal species. Xanthine oxidase has been suggested to be involved in the pathogenesis of post-ischemic reperfusion tissue injury through the generation of reactive oxygen species, while the extensive tissue localization of xanthine dehydrogenase/oxidase suggests several other roles for this enzyme, including a protective barrier against bacterial infection by producing either superoxide radicals or uric acid. Furthermore, an involvement in cellular proliferation and differentiation has been suggested. Urate oxidase is generally considered a liver-specific enzyme, except for bovines which possess this enzyme in the kidney. Urate oxidase is exclusively located in the peroxisomes of fish, frogs, and rats, but was lost in birds, some reptiles, and primates during evolution. A histochemical demonstration of allantoin-degrading enzymes has not been performed, but these enzymes have been located in peroxisomes by sucrose density gradient centrifugation. AMP deaminase activity is higher in skeletal muscle than in any other tissues. AMP deaminase may be involved in a number of physiological processes, such as the conversion of adenine nucleotide to inosine or guanine nucleotide, stabilizing the adenylate energy charge, and the reaction of the purine nucleotide cycle. There are three distinct isozymes (A, B, C) with different kinetic, physical, and immunological properties. Isozymes A, B, C have been isolated from muscle, liver (kidney), and heart tissue, respectively. In the muscle, AMP deaminase isozymes exist in a different part, suggesting a multiple functional role of this enzyme. High hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity is found in some regions of a normal adult human brain. However, very little is known regarding the histochemical tissue localization of HGPRT. Immunohistochemical localization of its developmental expression suggests that HGPRT may not be essential for purine nucleotide supplement in the segmentation of brain cells, but may play a significant role in the developing hippocampus.
 ...
PMID:Enzymes involved in purine metabolism--a review of histochemical localization and functional implications. 1050 47


<< Previous 1 2