HGPRTase hypoxanthine-guanine

The free bases of the purines can be salvaged to spare de novo synthesis. The only hard thing is remembering what the names stand for. HGPRTase is hypoxanthine-guanine phosphoribosyltransferase, and it makes both IMP and GMP. A separate enzyme exists for the salvage of adenine. The salvage pathways are included in Fig. 19-1. 

The Lesch-Nyhan syndrome is caused by a deficiency of the phosphoribosyltransferase that is involved in the salvage pathway for hypoxanthine and guanine (HGPRTase). The accumulation of P-Rib-PP stimulates purine biosynthesis. 

Salvage pathway is a useful term to refer to that collection of biochemical reactions whose transformations result in the phosphorylation of purines. As a consequence of this phosphorylation, purines are not secreted by cells but, in fact, are returned to the cellular metabolic pool. One of these salvage enzymes is hypoxanthine-guanine phosphoribosyltransferase (HGPRTase),... 

Mechanisms of action and resistance Mercaptopurine and thioguanine are purine antimetabolites. Both drugs are activated by hypoxanthine-guanine phosphoribosyltrans-ferases (HGPRTases) to toxic nucleotides that inhibit several enzymes involved in purine... 

A) Resistance to fluorouracil occurs via decreased activity of hypoxanthine-guanine phos-phoribosyl transferase (HGPRTase)... 

The abbreviations are as follows HGPRTase = hypoxanthine-guanine phosphoribosyltransferase P TR ase = nucleoside phosphotransferase APRTase = adenine phosphoribosyltransferase ASS3m-Lyase = adenylosuccinate synthetase-lyase. 

STUDIES OF THE EFFECT OF pH ON THE ERYTHROCYTIC HYPOXANTHINE-GUANINE PHOSPHORIBOSYL TRANSFERASE (HGPRTase) REACTION... 

The reaction mixture contained 50 /xM guanine, 50 fiM hypoxanthine, 100 /xM PRibPP, and 1 mM MgCh in potassium phosphate (pH 7.4). The reaction was initiated by the addition of the HGPRTase activity. An intervals the reaction was terminated by heating in a boiling water bath for 1 minute. Denatured protein was removed by centrifugation, and the sample was purified... 

There are three distinct PRTases in L. donovani (30). One has its major activity with hypoxanthine and guanine a second with adenine and a third with xanthine. Pyrazolo (3,4-d)pyrimidines, such as allopurinol, are efficient substrates for the HGPRtase. Promastigotes accumulate large quantities of allopurinol ribonucleoside-5 -phosphate when exposed to allopurinol (31). A separate PRTase for xanthine is unusual in a eukaryotic cell. XPRTase is also present in L. mexicana and L. amazonensis as well as in four non-pathogenic trypanosomatids (32,33). 

The schistosomule HGPRTase has been purified and characterized (68). It is twice as active with guanine as with hypoxanthine and cannot use xanthine. The gene for this protein has been cloned and expressed at a high level in Escherchia coli (69). 

In view of the fact that a number of hypoxanthine and guanine analogs are excellent substrates for erythrocytic HGPRTase and the... 

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