A review of HPRT and its emerging role in cancer

Townsend, Michelle H.; Robison, Richard A.; O’Neill, Kim L.

doi:10.1007/s12032-018-1144-1

Cited by 62 publications

(43 citation statements)

References 60 publications

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“…The present study showed that men who were being treated with an XOR inhibitor had a significantly higher level of xanthine, but not hypoxanthine, than that in men without treatment. Hypoxanthine is simultaneously metabolized to a purine nucleotide, inosine monophosphate, by HGPRT in the salvage pathway of purine metabolism, which recycles the basic materials for reconstitution of DNA, RNA and purine nucleotides, including adenosine triphosphate, without adenosine triphosphate expenditure, and cooperates with the de novo pathway of purine metabolism. Normally, approximately 90% of hypoxanthine is reutilized and converted to inosine monophosphate through the salvage pathway.…”

Section: Discussionmentioning

confidence: 99%

Differential regulation of hypoxanthine and xanthine by obesity in a general population

Furuhashi

Koyama

Higashiura

et al. 2020

J of Diabetes Invest

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Aims/Introduction: Uric acid is synthesized by oxidation of hypoxanthine and xanthine using a catalyzing enzyme, xanthine oxidoreductase (XOR), which can be a source of reactive oxygen species. Plasma XOR activity is a metabolic biomarker associated with obesity, hyperuricemia, liver dysfunction and insulin resistance. However, it has recently been reported that XOR activity in fat tissue is low in humans, unlike in rodents, and that hypoxanthine is secreted from human fat tissue. Materials and Methods: The associations of obesity with hypoxanthine, xanthine and plasma XOR activity were investigated in 484 participants (men/women: 224/260) of the Tanno-Sobetsu Study. Results: Levels of hypoxanthine, xanthine and plasma XOR activity were significantly higher in men than in women. In 59 participants with hyperuricemia, 11 (men/women: 11/0) participants were being treated with an XOR inhibitor and had a significantly higher level of xanthine, but not hypoxanthine, than that in participants without treatment. In all of the participants, hypoxanthine concentration in smokers was significantly higher than that in non-smokers. Stepwise and multivariate regression analyses showed that body mass index, smoking habit and xanthine were independent predictors of hypoxanthine after adjustment of age, sex and use of antihyperuricemic drugs. Whereas, alanine transaminase, hypoxanthine and plasma XOR activity were independent predictors for xanthine, and alanine transaminase, triglycerides and xanthine were independent predictors for plasma XOR activity. Conclusions: The concentration of hypoxanthine, but not that of xanthine, is independently associated with obesity and smoking habit, indicating differential regulation of hypoxanthine and xanthine in a general population.

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Section: Discussionmentioning

confidence: 99%

Differential regulation of hypoxanthine and xanthine by obesity in a general population

Furuhashi

Koyama

Higashiura

et al. 2020

J of Diabetes Invest

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“…A surface expression of HPRT has been reported in lung cancer cell lines, although the reason for this external presentation is presently unknown [ 160 ]. As HPRT is a potential cancer-associated antigen, the authors hypothesize that HPRT could become a target for emerging immunotherapies designed to attack cancer cells which display unique surface proteins [ 161 ].…”

Section: Hypoxanthine-guanine Phosphoribosyltransferase (Hprt)mentioning

confidence: 99%

Emerging Role of Purine Metabolizing Enzymes in Brain Function and Tumors

Garcia‐Gil

Camici²,

Allegrini³

et al. 2018

IJMS

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The growing evidence of the involvement of purine compounds in signaling, of nucleotide imbalance in tumorigenesis, the discovery of purinosome and its regulation, cast new light on purine metabolism, indicating that well known biochemical pathways may still surprise. Adenosine deaminase is important not only to preserve functionality of immune system but also to ensure a correct development and function of central nervous system, probably because its activity regulates the extracellular concentration of adenosine and therefore its function in brain. A lot of work has been done on extracellular 5′-nucleotidase and its involvement in the purinergic signaling, but also intracellular nucleotidases, which regulate the purine nucleotide homeostasis, play unexpected roles, not only in tumorigenesis but also in brain function. Hypoxanthine guanine phosphoribosyl transferase (HPRT) appears to have a role in the purinosome formation and, therefore, in the regulation of purine synthesis rate during cell cycle with implications in brain development and tumors. The final product of purine catabolism, uric acid, also plays a recently highlighted novel role. In this review, we discuss the molecular mechanisms underlying the pathological manifestations of purine dysmetabolisms, focusing on the newly described/hypothesized roles of cytosolic 5′-nucleotidase II, adenosine kinase, adenosine deaminase, HPRT, and xanthine oxidase.

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“…A four- and two-fold increase in HDAC2 and HDAC3, respectively, have been confirmed in ME/CFS cases [6] and a very high level of HDAC1 and HDAC2 binding sites occur within the genes upregulated in ME/CFS cases following exercise (see Table S1) [7]. The enzyme hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) is an important enzyme in the salvage of the purines, adenosine and guanine [24]. Its gene ( HPRT1 ) is on the X chromosome and has an unusual regulatory issue.…”

Section: Discussionmentioning

confidence: 99%

Post-Exertional Malaise Is Associated with Hypermetabolism, Hypoacetylation and Purine Metabolism Deregulation in ME/CFS Cases

McGregor

Armstrong²,

Lewis

et al. 2019

Diagnostics

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Post-exertional malaise (PEM) is a cardinal predictive symptom in the definition of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). If the cases overexert themselves they have what is termed “payback” resulting in a worsening of symptoms or relapse which can last for days, weeks or even months. The aim was to assess the changes in biochemistry associated with the cases self-reported PEM scores over a 7-day period and the frequency of reporting over a 12-month period. Forty-seven ME/CFS cases and age/sex-matched controls had a clinical examination, completed questionnaires; were subjected to standard serum biochemistry; had their serum and urine metabolomes analyzed in an observational study. Thirty-five of the 46 ME/CFS cases reported PEM in the last 7-days and these were allocated to the PEM group. The principal biochemical change related to the 7-day severity of PEM was the fall in the purine metabolite, hypoxanthine. This decrease correlated with alterations in the glucose:lactate ratio highly suggestive of a glycolytic anomaly. Increased excretion of urine metabolites within the 7-day response period indicated a hypermetabolic event was occurring. Increases in urine excretion of methylhistidine (muscle protein degradation), mannitol (intestinal barrier deregulation) and acetate were noted with the hypermetabolic event. These data indicate hypoacetylation was occurring, which may also be related to deregulation of multiple cytoplasmic enzymes and DNA histone regulation. These findings suggest the primary events associated with PEM were due to hypoacetylation and metabolite loss during the acute PEM response.

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A review of HPRT and its emerging role in cancer

Cited by 62 publications

References 60 publications

Differential regulation of hypoxanthine and xanthine by obesity in a general population

Differential regulation of hypoxanthine and xanthine by obesity in a general population

Emerging Role of Purine Metabolizing Enzymes in Brain Function and Tumors

Post-Exertional Malaise Is Associated with Hypermetabolism, Hypoacetylation and Purine Metabolism Deregulation in ME/CFS Cases

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