The metabolism of carbohydrates is largely determined by their chemical properties. Glucose may have been selected, over the other aldohexoses, because of its low propensity for glycation of proteins. That carbohydrate is stored in polymeric form (glycogen) is dictated by osmotic pressure considerations. That stored fat is about eight times more calorically dense than glycogen, when attendant water is factored in, accounts for the predominance of fat as a storage form of calories and, also, for the fact that ingested carbohydrate is oxidized promptly (that is, fuel of the fed state) rather than being extensively stored. That stored glycogen is accompanied by so much water accounts for the fact that the brain only has very small glycogen stores. Carbohydrate has two important advantages, over fat, as a metabolic fuel; it is the only fuel that can produce ATP in the absence of oxygen, and more ATP is produced per O 2 consumed when glucose is oxidized, compared with when fat is oxidized. These advantages probably determine the preference of many cell types for carbohydrate. In addition to its use as a metabolic fuel, glucose plays other important roles such as provision of NADPH via the pentose phosphate pathway, and as a source material for the synthesis of other key carbohydrates, for example, ribose and deoxyribose for nucleic acid synthesis and substrates for the synthesis of glycoproteins, glycolipids and glycosaminoglycans. It can also play a key role in anaplerosis. Although it is widely acknowledged that gluconeogenesis plays a crucial role in starvation it is now apparent that prandial gluconeogenesis occurs, both in the metabolic disposal of dietary amino acids and in the synthesis of glycogen by the indirect pathway. Although there is, strictly speaking, no dietary requirement for carbohydrate it is evident that glucose is a universal fuel for probably all cells in the body and carbohydrate is the cheapest source of calories and the major source of dietary ®bre. These observations, together with the fact that glucose is the preferred metabolic fuel for the brain, permit us to recommend appreciable quantities of carbohydrate in all prudent diets. Why carbohydrate?Since fat has a much higher caloric density than carbohydrate it is worth considering, at the outset, why we have a carbohydrate metabolism. Without question, this is due to the fact that carbohydrate is the primary product of photosynthesis and, since heterotrophic animals obtain their energy from autotrophic organisms, it was inevitable that they evolved a metabolism that extracted useful energy from the most abundantly available carbon source Ð carbohydrate. Why did glucose, of all the sugars, become the primary carbohydrate for energy metabolism? Precise answers to such a question are not readily available but it must be pointed out that glucose has the lowest proportion of straight-chain (non-ring) structure of all the aldohexoses. This minimizes non-enzymatic protein glycation and, indeed, Bunn & Higgins (1981) have suggested that evolution...

The liver of diabetic animals removes increased quantities of glutamine. We therefore examined factors that affect hepatic glutaminase activity in hepatocytes and mitochondria. Glutamine use, through glutaminase, was measured in isolated rat hepatocytes by monitoring the production of 14CO2 from [1-(14)C]glutamine. Hepatocytes from streptozotocin-induced diabetic rats use glutamine more rapidly than do hepatocytes from normal or insulin-maintained diabetic rats. Glutamine use in all of these hepatocytes was stimulated by glucagon and epinephrine. Glutaminase activity, assayed in broken mitochondrial membranes, was increased approximately 2.5-fold in diabetic rats. The sensitivity of glutaminase, measured in intact liver mitochondria, to phosphate was markedly left-shifted in mitochondria from diabetic rats compared with those from controls. In fact, glutaminase was increased 10-fold at 2.5 mmol/l phosphate compared with controls. This increased sensitivity of glutaminase to physiological concentrations of phosphate is characteristic of its hormonal activation. Therefore, activation of glutaminase plays a major role in diabetes and is as important as increases in its total enzyme amount in determining the increased glutamine uptake in diabetes.

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Hormones which regulate hepatic oxidation of glycine include glucagon, catecholamines and vasopressin. The stimulation of oxidation of glycine by glucagon requires cyclic nucleotidedependent phosphorylation of one or more cytosolic proteins and does not involve mobilization of calcium from intracellular stores. The stimulation of glycine oxidation by catecholamines and vasopressin, on the other hand, appears to involve calcium mobilization. While calcium has direct effect on mitochondrial glycine oxidation, the link between phosphorylation of cytosolic protein(s) and mitochondrial glycine oxidation is not known. The stimulation of glycine oxidation by hormones can be demonstrated in mitochondria isolated from rats treated with hormones prior to sacrifice. Both the effects of glucagon and calcium are evident in isolated mitochondria only when inorganic phosphate is included in the medium. These findings are discussed in relation to the regulation of hepatic glycine oxidation.

BWOSNAN, J. T., and F m z , I. B. The oxidation of fatty-acyl derivatives by mitochondria from bovine fetal and calf hearts. Can. J. Biwhem. 49, 1296-1 300 (1971).Functional activity of the "external" carnitine palmitoyltransferase in intact mitochondria, prepared from hearts from various sources, was estimated by measuring respiration by mitochondria in the presence of palmitoyl-CoA plus or minus lamitine. When palmitoyl-CoA alone was substrate, respiration was not increased above the basal rate under all conditions examined. Addition of I-sarnitine increased respiration, provided the ionic strength of the incubation medium was sufficiently high. In the presence of palmitoyl-CoA plus I-carnitine, the rate of respiration increased as the ionic strength was increased to physio%ogicall levels. In contrast, the increase in rate of oxygen consumption by heart mitochondria which followed the addition of ps~lfnitoyl-lamitine was relatively independent of the ionic strength of the medim.Mitochondrid fractions prepared from fetal bovine hearts were shown to possess "exkrnal'"nitine palmitoyltrmsferase activity, as judged by the ability of I-carnitine to stimulate respiration by mitochondria incubated with palmitoyl-CoA under various conditions. These data were discussed in relation to information available concerning the functions of different carnitine acy%transferases in mitochondria. BWOSNAN, J. T., et FRITZ, I. B. The oxidation of fatty-acyl derivatives by mitochondria fmm bovine fetal and calf harts. Can. J. Biochem. 49,1296-1380 (1971).L'activitt fonctionnelle de la carnitine palmitoyltransf6rase "externe" b s les rnitochondries intact-, pr6pi4rh 2i partir de cx~urs provenant de sources diverses, est 6valuk en mawant la respiration mitochondriale era pdsence de palmitoyl-CoA avec ou sans I-arnitine. Avec le palnitoyl-&A sed c u m e substrat, la respiration ne depasse pas le taux de base dans toutes les conditions utilisks. L'addition de I-eaarnitine augmente la respiration poufvu que Ia force ionique cfra milieu d'incubation soit suffisament klevh. En prksence de palmitoyl-CoA et de I-carnitine, le t a w respiratoire augmente en rnerne temps que la force ionique atteint des taux physiulogiques. Au contraire, dans les mitochondries du coeur, I'augmentation du taux de consomation d'oxygbne consdcutive 2i l'addition de palmitoyl-I-camitine est relativement indkpendante de la force ionique du milieu.Les fractions mitochondriales prkparh B partir des ceurs de fetus de beuf posskdcnt m e eaarnitine palmitoyltransf$rase 'kxterne". En effet, la l-sarnitine peut stimuler la respiration des rnitochondlries incuMes avec le palrnitoyl-CoA sous diverses conditions. C%s dsultats sont discutks en rapport avec la litterature disponible concemant l a fonctions des diflkrentes carnitine acyltrmsftrases des mitochondries.

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