Metabolism substrate cycles

Newsholme, E., Challiss, R., and Crabtree, B., 1984. Substrate cycles Their role in improving sensitivity in metabolic control. Trends in Biochemical Sciences 9 277-280. 

One of these alternate models, postulated by Gunter Wachtershanser, involves an archaic version of the TCA cycle running in the reverse (reductive) direction. Reversal of the TCA cycle results in assimilation of CO9 and fixation of carbon as shown. For each turn of the reversed cycle, two carbons are fixed in the formation of isocitrate and two more are fixed in the reductive transformation of acetyl-CoA to oxaloacetate. Thus, for every succinate that enters the reversed cycle, two succinates are returned, making the cycle highly antocatalytic. Because TCA cycle intermediates are involved in many biosynthetic pathways (see Section 20.13), a reversed TCA cycle would be a bountiful and broad source of metabolic substrates. 

Substrate Cycles Provide Metabolic Control Mechanisms... 

Because substrate cycles such as this appear to operate with no net benefit to the cell, they were once regarded as metabolic quirks and were referred to as futile cycles. More recently, substrate cycles have been recognized as important devices for controlling metabolite concentrations. 

The gland is situated in the neck across the front of the trachea. It secretes thyroxine (T4), which is converted to the active form of the hormone, triiodothyronine (T3), in peripheral tissues. It stimulates metabolic activity in tissues so that it increases heat production (for example, by stimulating protein turnover and substrate cycles). 

Substrate cycling (e.g. the Cori cycle and the intra- and inter-cellular triacylglycerol/fatty acid cycles (Chapter 3)) in which there is no net metabolic change so that the energy from ATP hydrolysis is released as heat. 

Matthews, P.M., Foxall, D., Shen, L. and Mansour, T.E. (1 986) Nuclear magnetic resonance studies of carbohydrate metabolism and substrate cycling in Fasciola hepatica. Molecular Pharmacology 29, 65-73. 

Substrate Cycles Amplify Metabolic Signals and Produce Heat... 

E.A. Newsholme, Substrate cycles their metabolic, energetic and thermic consequences in man, Biochem. Soc. Symp., 1978, 43, 183-205. 

A pair of reactions such as the phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate and its hydrolysis back to fructose 6-phosphate is called a substrate cycle. As already mentioned, both reactions are not simultaneously fully active in most cells, because of reciprocal allosteric controls. However, isotope-labeling studies have shown that some fructose 6-phosphate is phosphorylated to fructose 1,6-bisphosphate even during gluconeogenesis. There also is a limited degree of cycling in other pairs of opposed irreversible reactions. This cycling was regarded as an imperfection in metabolic control, and so substrate cycles have sometimes been called... 

A number of control mechanisms operate in carbohydrate metabolism. They include allosteric effects, covalent modification, substrate cycles, and genetic control. These mechanisms affect key enzymes in different ways with different time responses. 

Explain how substrate cycles may amplify metabolic signals or produce heat. 

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