Enzymic micro-assay for blood glutamine.

It is thought that glycolysis is the predominant energy pathway in cancer, particularly in solid and poorly vascularized tumors where hypoxic regions develop. To evaluate whether glycolysis does effectively predominate for ATP supply and to identify the underlying biochemical mechanisms, the glycolytic and oxidative phosphorylation (OxPhos) fluxes, ATP/ADP ratio, phosphorylation potential, and expression and activity of relevant energy metabolism enzymes were determined in multi-cellular tumor spheroids, as a model of human solid tumors. In HeLa and Hek293 young-spheroids, the OxPhos flux and cytochrome c oxidase protein content and activity were similar to those observed in monolayer cultured cells, whereas the glycolytic flux increased two- to fourfold; the contribution of OxPhos to ATP supply was 60%. In contrast, in old-spheroids, OxPhos, ATP content, ATP/ADP ratio, and phosphorylation potential diminished 50-70%, as well as the activity (88%) and content (3 times) of cytochrome c oxidase. Glycolysis and hexokinase increased significantly (both, 4 times); consequently glycolysis was the predominant pathway for ATP supply (80%). These changes were associated with an increase (3.3 times) in the HIF-1alpha content. After chronic exposure, both oxidative and glycolytic inhibitors blocked spheroid growth, although the glycolytic inhibitors, 2-deoxyglucose and gossypol (IC(50) of 15-17 nM), were more potent than the mitochondrial inhibitors, casiopeina II-gly, laherradurin, and rhodamine 123 (IC(50) > 100 nM). These results suggest that glycolysis and OxPhos might be considered as metabolic targets to diminish cellular proliferation in poorly vascularized, hypoxic solid tumors.

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Energy metabolism transition in multi‐cellular human tumor spheroids

Rodrı́guez-Enrı́quez

Gallardo‐Pérez

Avilés‐Salas

et al. 2008

Journal Cellular Physiology

124

101

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Intestinal ammonium production in the rat: The role of the colon, small intestine, and circulating glutamine

et al. 1988

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The intestinal ammonium production and the intestinal uptake of circulating glutamine were investigated in anesthetized intact rats and rats with resected small intestine or colon by simultaneous measurements performed on portal and arterial blood. It was shown that ammonium release into the portal blood by the small intestine is of equal magnitude to that released by the colon, and that circulating glutamine participates in ammonium production by the small intestine. Increased levels of circulating glutamine induced by its i.v. infusion to intact rats were not accompanied by an increase in intestinal ammonium production.

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Arterial ammonemia changes of renal origin induced in the rat by acid and alkaline diets

et al. 1986

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The aim of this study was to investigate the influence of acid and alkali food supplementation on systemic ammonemia to explain the hyperammonemia previously observed in rats fed a high protein diet. In normal rats, arterial ammonia concentration significantly increases after 4 days of HCl-supplemented diet. Following a NaHCO3-enriched food, there is only a slight but not significant decrease in arterial ammonia level. These changes occur before any variation in arterial acid-base status and are of renal origin. Indeed, there is a positive linear correlation (r = 0.946; P less than 0.001) between arterial ammonia level and the ammonia concentration difference between the renal vein and artery (which varies proportionally to the urinary ammonium excretion). Hindquarter uptake and intestinal release of ammonia do not significantly participate in the arterial ammonia changes observed. Following HCl-enriched diets, increased renal glutamine uptake, enhanced hindquarter glutamine release, and perhaps decreased intestinal glutamine uptake occur simultaneously. In conclusion, acid and alkali food supplementation intervenes on the renal ammonia release into the circulation with concomitant arterial ammonemia changes.

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Enzymic micro-assay for blood glutamine.

Cited by 13 publications

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Energy metabolism transition in multi‐cellular human tumor spheroids

Energy metabolism transition in multi‐cellular human tumor spheroids

Intestinal ammonium production in the rat: The role of the colon, small intestine, and circulating glutamine

Arterial ammonemia changes of renal origin induced in the rat by acid and alkaline diets

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