The interrelationships of hormones, fatty acid and glucose in the provision of energy

PJ Randle - Postgraduate Medical Journal, 1964 - ncbi.nlm.nih.gov
PJ Randle
Postgraduate Medical Journal, 1964ncbi.nlm.nih.gov
AN important and characteristic property of living matter is its ability to transfer energy
released from the breakdown of foodstuffs to other energy-requiring processes such as the
synthesis of cell materials or the performance of work. The energy transfer is effected by
chemical substances chief amongst which are nucleoside triphosphates such as ATP
(adenosine triphosphate) and for reductive syntheses (such as fatty acid or steroid
synthesis) re-duced coenzymes (abbreviated as NADH2 or NADPH2 which are reduced …
AN important and characteristic property of living matter is its ability to transfer energy released from the breakdown of foodstuffs to other energy-requiring processes such as the synthesis of cell materials or the performance of work. The energy transfer is effected by chemical substances chief amongst which are nucleoside triphosphates such as ATP (adenosine triphosphate) and for reductive syntheses (such as fatty acid or steroid synthesis) re-duced coenzymes (abbreviated as NADH2 or NADPH2 which are reduced coenzyme I and II respectively). In mammalian cells ATP and reduced coenzymes are generated for the most part by respiration and the major fuels for respiration are glucose and fatty acids and ketone bodies. These reactions, concerned with the formation and utilisation of ATP and re-duced coenzymes, constitute what is known as energymetabolism in cells. Their control necessarily plays an important part in the overall regulation of cell metabolism. This chapter is concerned largely with the importance ofthe control of energy metabolism in mammailian muscle to the actions of hormones and to the metabolic disturbances of diaibetes and other endocrinedisorders. The discussion will be confined to the ways in which cells increase or decrease the production of ATP and reduced coenzymes according to needs and with the ways in which cell metabolism is adjusted by the availability of glucose, fatty acids and oxygen. Together these processes comprise what is known collectively as respirat-ory control. To discuss the reactions involved in tihe use of ATP and reduced coenzymes is beyond the scope of this chapter but it may be noted that one or both participate in the synthesis of all major cell constituents (nucleic acids, proteins, lipids, carbohydrates and coenzymes) and in such major physiological processes as muscular contraction, the passage of nerve impulses and the movements of ions, amino acids and sugars across cell mentbranes against concentration gradients. Respiratory control in muscle comprises three distinct but related processes. The first is concerned with the control of oxygen con-sumption. In healthy cells the consumption of oxygen is presumably controlled by therate of ATP utilisation and mediatedby the con-centration of ADP (adenosine diphosphate) formed in the utilisation of ATP (Chance, 1959). The second type of respiratory control is concerned with the regulation of rates of glycolysis and glucose uptake by the intracellular concentration of ATP. This type of control was first observed by Pasteur who noted that glycolysis in yeast is greater in the absence of oxygen than in its presence. It is now recognised that the Pasteur effect (the inhibition of glycolysis iby respiration) is exhibited by most cells and tissues including muscle (Randle, 1956; Morgan, Randle and Regen, 1959). It has been attrilbuted to the fact that anaerobic metabolism of glucose yields less ATP than aerobic metabolism (Randle and Smith, 1958a). In keeping with this it was observed that drugs such as salicylate or 2: 4-dinitrophenol (which interfere with the synthesis of ATP by respiration) accelerate glucose uptake and glycolysis. As will be seen later the reactions involved in the control of glycolysis may be directly controlled by the intracellular con-centration of ATP and of its breakdown products 5'AMP (adenosine mono-phosphate) and Pi (inorganic phosphate). The third type of respiratory control is concerned with the inter-actions of glucose and fatty acid metabolism. In musele the provision of fatty acids or ketone bodies for respiration can impair the oxtidation of glucose (Drury and Wick, 1953) and diminish glucose uptake and glycolysis …
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