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INTRODUCTION

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OBJECTIVES

After studying this chapter, you should be able to:

  • Explain what is meant by anabolic, catabolic, and amphibolic metabolic pathways.

  • Describe in outline the metabolism of carbohydrates, lipids, and amino acids at the level of tissues and organs, and at the subcellular level, and the interconversion of metabolic fuels.

  • Describe the ways in which flux of metabolites through metabolic pathways is regulated.

  • Describe how a supply of metabolic fuels is provided in the fed and fasting states; the formation of metabolic fuels reserves in the fed state and their mobilization in fasting.

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BIOMEDICAL IMPORTANCE

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Metabolism is the term used to describe the interconversion of chemical compounds in the body, the pathways taken by individual molecules, their interrelationships, and the mechanisms that regulate the flow of metabolites through the pathways. Metabolic pathways fall into three categories. (1) Anabolic pathways, which are those involved in the synthesis of larger and more complex compounds from smaller precursors—for example, the synthesis of protein from amino acids and the synthesis of reserves of triacylglycerol and glycogen. Anabolic pathways are endothermic. (2) Catabolic pathways, which are involved in the breakdown of larger molecules, commonly involving oxidative reactions; they are exothermic, producing reducing equivalents, and, mainly via the respiratory chain (see Chapter 13), ATP. (3) Amphibolic pathways, which occur at the “crossroads” of metabolism, acting as links between the anabolic and catabolic pathways, for example, the citric acid cycle (see Chapter 16).

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Knowledge of normal metabolism is essential for an understanding of abnormalities that underlie disease. Normal metabolism includes adaptation to periods of fasting, starvation, and exercise, as well as pregnancy and lactation. Abnormal metabolism may result from nutritional deficiency, enzyme deficiency, abnormal secretion of hormones, or the actions of drugs and toxins.

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A 70-kg adult human being requires about 8 to 12 MJ (1920-2900 kcal) from metabolic fuels each day, depending on physical activity. Larger animals require less per kilogram body weight, and smaller animals more. Growing children and animals have a proportionally higher requirement to allow for the energy cost of growth. For human beings, this energy requirement is met from carbohydrates (40%-60%), lipids (mainly triacylglycerol, 30%-40%), and protein (10%-15%), as well as alcohol. The mix of carbohydrate, lipid, and protein being oxidized varies, depending on whether the subject is in the fed or fasting state, and on the duration and intensity of physical work.

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There is a constant requirement for metabolic fuels throughout the day; average physical activity increases metabolic rate only by about 40% to 50% over the basal or resting metabolic rate. However, most people consume their daily intake of metabolic fuels in two or three meals, so there is a need to form reserves of carbohydrate (glycogen in liver and muscle), lipid (triacylglycerol in adipose tissue), and labile protein stores during the period following a meal, for use during the intervening time when there ...

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