Marks’ Basic Medical Biochemistry: A Clinical Approach Second Edition

Book Preface

In order to survive, humans must meet two basic metabolic requirements: we must be able to synthesize everything our cells need that is not supplied by our diet, and we must be able to protect our internal environment from toxins and changing conditions in our external environment. In order to meet these requirements, we metabolize our dietary components through four basic types of pathways: fuel oxidative pathways, fuel storage and mobilization pathways, biosynthetic pathways, and detoxification or waste disposal pathways. Cooperation between tissues and responses to changes in our external environment are communicated though transport pathways and intercellular signaling pathways (Fig. I.1). The foods in our diet are the fuels that supply us with energy in the form of calories. This energy is used for carrying out diverse functions such as moving, thinking, and reproducing. Thus, a number of our metabolic pathways are fuel oxidative pathways that convert fuels into energy that can be used for biosynthetic and mechanical work. But what is the source of energy when we are not eating— between meals, and while we sleep? How does the hunger striker in the morning headlines survive so long? We have other metabolic pathways that are fuel storage pathways. The fuels that we store can be molibized during periods when we are not eating or when we need increased energy for exercise. Our diet also must contain the compounds we cannot synthesize, as well as all the basic building blocks for compounds we do synthesize in our biosynthetic pathways.

For example we have dietary requirements for some amino acids, but we can synthesize other amino acids from our fuels and a dietary nitrogen precursor. The compounds required in our diet for biosynthetic pathways include certain amino acids, vitamins, and essential fatty acids. Detoxification pathways and waste disposal pathways are metabolic pathways devoted to removing toxins that can be present in our diets or in the air we breathe, introduced into our bodies as drugs, or generated internally from the metabolism of dietary components. Dietary components that have no value to the body, and must be disposed of, are called xenobiotics.

In general, biosynthetic pathways (including fuel storage) are referred to as anabolic pathways, that is, pathways that synthesize larger molecules from smaller components. The synthesis of proteins from amino acids is an example of an anabolic pathway. Catabolic pathways are those pathways that break down larger molecules into smaller components. Fuel oxidative pathways are examples of catabolic pathways.

In the human, the need for different cells to carry out different functions has resulted in cell and tissue specialization in metabolism. For example, our adipose tissue is a specialized site for the storage of fat and contains the metabolic pathways that allow it to carry out this function. However, adipose tissue is lacking many of the pathways that synthesize required compounds from dietary precursors. To enable our cells to cooperate in meeting our metabolic needs during changing conditions of diet, sleep, activity, and health, we need transport pathways into the blood and between tissues and intercellular signaling pathways. One means of communication is for hormones to carry signals to tissues about our dietary state. For example, a message that we have just had a meal, carried by the hormone insulin, signals adipose tissue to store fat.

In the following section, we will provide an overview of various types of dietary components and examples of the pathways involved in utilizing these components. We will describe the fuels in our diet, the compounds produced by their digestion, and the basic patterns of fuel metabolism in the tissues of our bodies. We will describe how these patterns change when we eat, when we fast for a short time, and when we starve for prolonged periods. Patients with medical problems that involve an inability to deal normally with fuels will be introduced. These patients will appear repeatedly throughout the book and will be joined by other patients as we delve deeper into biochemistry.