Comments on metabolic needs for glucose and the role of gluconeogenesis

Abstract

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...

Energy metabolism and fasting in male and female insectivorous bats Molossus molossus (Chiroptera: Molossidae)

“…In this way, several studies have demonstrated that vertebrates consuming carbohydrate-rich diets, including fruit-eating bats, present increased liver glycogen levels and fat reserves when fed. Following short-term fasting, these animals show a decrease in plasma glucose, but the maintenance of glycemic homeostasis as fasting continues, mainly through liver glycogenolysis and gluconeogenesis (Kettelhut et al, 1980;Sartori et al, 1995;Brosnan, 1999;Turner et al, 1999;Tirone and Brunicardi, 2001;Pinheiro et al, 2006). However, an exception to this pattern has been reported for meadow voles (Microtus pennsylvanicus, Clethrionomys rutilus and Clethrionomys rufocanus).…”

Mechanisms by Which Liver-Specific PEPCK Knockout Mice Preserve Euglycemia During Starvation

“…Moreover, the abundance of mRNA encoding the mitochondrial dicarboxylate carrier protein, a component of the inner mitochondria membrane responsible for transporting malate and succinate across the inner membrane in exchange for phosphate, sulfate, or thiosulfate (21), is increased 3.5-fold during fasting (data not shown). Because the operation of anaplerotic reactions requires the coexistence of cataplerotic reactions (22), it is likely that the elevated hepatic gene expression for the above proteins leads to a net release of glutamine from the liver to the blood as a response to the blockage of hepatic gluconeogenesis from TCA cycle intermediates in these knockout animals. Thus, although the liver is incapable of producing much glucose in the absence of hepatic PEPCK, this does not mean that it ceases to be metabolically involved in maintaining glucose homeostasis.…”

Late evening snack: Exploiting a period of anabolic opportunity in cirrhosis

“…[13][14][15] Cirrhosis is characterized by a state of accelerated starvation, with an early shift from glucose to lipid utilization for energy during the postabsorptive state. 19 This accelerates skeletal muscle protein loss and reduces MPS, resulting in sarcopenia. In healthy subjects, this metabolic profile develops only after 2 to 3 days of fasting.…”