The resurgence of research into cancer metabolism has recently broadened interests beyond glucose and the Warburg effect to other nutrients, including glutamine. Because oncogenic alterations of metabolism render cancer cells addicted to nutrients, pathways involved in glycolysis or glutaminolysis could be exploited for therapeutic purposes. In this Review, we provide an updated overview of glutamine metabolism and its involvement in tumorigenesis in vitro and in vivo, and explore the recent potential applications of basic science discoveries in the clinical setting.

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From Krebs to clinic: glutamine metabolism to cancer therapy.

Body size and tissue respiration

Enzyme secretion and the incorporation of p32 into phospholipides of pancreas slices

Publisher Summary It is now recognized that a number of factors can influence the uptake of glucose by muscle. Some are of physiological importance and these include hormones, notably insulin, growth hormone, corticosteroids, and adrenaline and possibly thyroxine and glucagon, and nonhormonal factors such as the availability of oxygen, the contractile activity of the tissue, the concentration of glucose in extracellular water, arid the availability for respiration of other substrates, such as ketone bodies and fatty acids. Other factors that influence glucose uptake arc of interest because of their hypoglycemic effects in diabetic patients and animals, notably salicylate and 2 ,4-dinitrophenol. The uptake of glucose by muscle is a complex process, which is thought to involve, in sequence, passage of the sugar from capillaries to the muscle cell membrane, transfer across the cell membrane, and metabolism within the cell by multienzyme systems with their various cofactors.

Regulation of Glucose Uptake by Muscle

The purpose of this study was to use a direct method, that of electron spin resonance (ESR) spectroscopy, to demonstrate that reperfusion after a period of ischemia results in a sudden increase in the production of free radicals in the myocardium. The isolated buffer-perfused rat heart was used with N-tert-butyl-alpha-phenylnitrone (PBN) as a spin-trapping agent. Samples of coronary effluent were taken and extracted into toluene for detection of radical adducts by ESR spectroscopy. After 15 minutes of total, global ischemia, aerobic reperfusion resulted in a sudden burst of radical formation that peaked at 4 minutes. When hearts were reperfused with anoxic buffer, no dramatic increase in radical production was observed. Subsequent reintroduction of oxygen, however, resulted in an immediate burst of radical production of a similar magnitude to that seen in the wholly aerobic reperfusion experiments. The ESR signals obtained (aN = 13.60 G, aH = 1.56 G) are consistent with the spin-trapping by PBN of either a carbon-centered species or an alkoxyl radical, both of which could be formed by secondary reactions of initially-formed oxygen radicals with membrane lipid components.

Direct detection of free radicals in the reperfused rat heart using electron spin resonance spectroscopy.

Das Hauptergebnis dieser Arbeit ist die Auffindung des Weges, auf dem im tierischen Organismus die Synthese des Harnstoffs aus Ammoniak und Kohlensaure verlauft. Die Harnstoffsynthese ist an das Vorhandensein von Ornithin gebunden, ohne das Ornithin in der Bilanz der Synthese verbraucht wird. Ornithin, Ammoniak und Kohlensaure treten unter Wasseraustritt zu einer Guanidinoverbindung — dem Arginin — zusammen [Reaktion (1)]. Arginin spaltet durch die Wirkungder Arginase Harnstoffab [Reaktion (2)] und liefert Ornithin zuruck, das wieder fur Reaktion (1) zur Verfugung steht.

Kurt Henseleit

Papers

Untersuchungen uber die Harnstoffbildung im Tierkörper

Untersuchungen über die Harnstoffbildung im Tierkörper