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Chapter: Biochemistry: Integration of Metabolism: Cellular Signaling

Biochemistry and Nutrition

The molecules that we process by catabolic reactions ultimately come from outside the body because we are heterotrophic organisms (dependent on external food sources).

Biochemistry and Nutrition

The molecules that we process by catabolic reactions ultimately come from outside the body because we are heterotrophic organisms (dependent on external food sources).

What are required nutrients?

In humans, the catabolism of macronutrients (carbohydrates, fats, and proteins) to supply energy is an important aspect of nutrition. In the United States, most diets provide more than an adequate number of nutritional calories. The typical American diet is high enough in fat that essential fatty acids  are seldom, if ever, deficient. The only concern is that the diet contains an adequate supply of protein. If the intake of protein is sufficient, the supply of essential amino acids  is normally also sufficient. 

Packaging on food items frequently lists the protein content in terms of both the number of grams of protein and the percentage of the daily value (DV) suggested by the Food and Nutrition Board under the auspices of the National Research Council of the National Academy of Sciences (see Table 24.1). Daily values have replaced the recommended daily allowances (RDAs) formerly seen on food packaging.

There are some key biochemical concepts to remember when analyzing a diet for protein content. First, there is no storage form for proteins. This means that proteins eaten in excess do a person no good in terms of satisfying that person’s future protein requirements. All protein consumed in excess of what is needed is turned into carbohydrate or fat, and the nitrogen from the amino group must be eliminated through the urea cycle. Ingesting too much protein can therefore be stressful on the liver and kidneys because of the overproduction of ammonia that must be eliminated. 

This is the same risk faced by certain athletes who take creatine to build muscles, because creatine is a highly nitrogenated compound.

Second, the essential amino acids must be consumed daily in order for proteins to be made. It would be difficult to find a protein that did not have at least one residue of each of the common 20 amino acids. Half of these amino acids are essential, and if the diet is lacking or low in even one of these essential amino acids, then protein synthesis is not possible. Not all proteins are cre-ated equal. The protein efficiency ratio (PER) is an indication of how complete a protein is. However, mixing proteins correctly is very important, something that vegetarians know a lot about. A protein that is very low in lysine would have a low PER value. If a second protein had a low PER because it was low in tryptophan, it could be combined with the low-lysine protein to give a combination with a high PER. However, this would work only if the two were eaten together.

Third, proteins are always being degraded. Because of that, even if a person does not seem to be doing any activities that would tend to require protein replenishment, there is a constant need for quality protein in order to maintain the body’s structures. Athletes are painfully aware of that fact. They must train constantly, and they get out of shape quickly when they stop, the effect being even more pronounced as the athlete reaches middle age.

Why do we need vitamins?

Micronutrients (vitamins and minerals) are also listed on food packaging. Thevitamins we require are compounds that are necessary for metabolic processes; either our bodies cannot synthesize them, or they cannot synthesize them in amounts sufficient for our needs. As a result, we must obtain vitamins from dietary sources. DVs are listed for the fat-soluble vitamins—vitamins A, D, and E—but care must be taken to avoid overdoses of these vitamins. Excesses can be toxic when large amounts of fat-soluble vitamins accumulate in adipose tissue. Excess vitamin A is especially toxic. With water-soluble vitamins, turnover is frequent enough that the danger of excess is not normally a problem.

The water-soluble vitamins with listed DVs are vitamin C, which is necessary for the prevention of scurvy, and the B vitamins—niacin, panto-thenic acid, vitamin B6, riboflavin, thiamine, folic acid, biotin, and vitamin B12. The B vitamins are the precursors of the metabolically important coenzymes listed in Table 7.1, where references to the reactions in which the coenzymes play a role are given. We have seen many pathways in which NADH, NADPH, FAD, TPP, biotin, pyridoxal phosphate, and coenzyme A were found, all of which came from vitamins. A summary of vitamins and their metabolic roles is given in Table 24.2. Frequently, the actual biochemical role is played by a metabolite of the vitamin rather than by the vitamin itself, but this point does not affect the dietary requirement.

What are minerals?

Minerals, in the nutritional sense, are inorganic substances required in theionic or free-element form for life processes. The macrominerals (those needed in the largest amounts) are sodium, potassium, chloride, magnesium, phosphorus, and calcium. The required amounts of all these minerals, except calcium, can easily be satisfied by a normal diet. 

Deficiencies of calcium can,  Calcium deficiencies can lead to bone fragility, with concomitant risk of fracture, which is a problem especially for elderly women. Calcium supplements are indicated in such cases. Requirements for some microminerals (trace minerals) are not always clear. It is known, for example, from biochemical evidence that chromium is necessary for glucose metabolism (a role that has recently been suggested for chromium picolinate) and that manganese is necessary for bone formation, but no deficiencies of these elements have been recorded. Requirements have been established for iron, copper, zinc, iodide, and fluoride; there are DVs for all of these minerals except fluoride. In the case of copper and zinc, needs are easily met by dietary sources, and overdoses can be toxic. A deficiency of iodide, leading to an enlarged thyroid gland, has been a problem in some parts of the United States for many years. Iodized salt is used to prevent this deficiency, and it has become unusual to find table salt without an iodine supplement. Fluoride is administered to prevent tooth decay in children and, with that end in mind, has been added to water supplies, sometimes causing considerable controversy. Iron is important because it is part of the structure of the ubiquitous heme proteins. Women of childbearing age are more susceptible to iron deficiencies than are other segments of the population, and in some cases supplements are advised. These recommended levels vary with the age of the individual and are subject to adjustment for level of activity.

The Food Pyramid

One approach to publicizing healthful food selection was the development of the Food Guide Pyramid, a graphic display that focuses on a diet sufficient in nutrients but without excesses (Figure 24.2). The goal was to use a well-chosen diet to promote good health. To avoid confusion, the development of this scheme had to take into account the fact that many people were familiar with the older recommendations about food groups. 

The newer recommendations pay particular attention to increasing the amount of fiber and decreasing the amount of fat in the typical diet. Variety and moderation were key concepts of the graphic presentation. From the biochemical point of view, these recommendations translate into a diet based primarily on carbohydrates, with enough protein to meet needs for essential amino acids. Note that in Figure 24.2, carbohydrates are the base, with the correct amount suggested to be 6 to 11 servings of foods rich in complex carbohydrates, such as bread, cereal, rice, or pasta. Lipids should not contribute more than 30% of daily calories, but the typical American diet currently is about 45% fat. High-fat diets have been linked to heart disease and to some kinds of cancer, so the recommendation about lipid intake is of considerable importance.

Is the old food pyramid still valid?

Many scientists are questioning some of the details of the food pyramid. Certain types of fat are essential to health and actually reduce the risk of heart disease. Also, there has been little evidence to back up the claim that a high intake of carbohydrates is beneficial. Many people feel that the original food pyramid, which was published in 1992, has serious flaws. It overglorifies carbohydrates while making all fats out to be the bad guys. In addition, meat, fish, poultry, and eggs are all lumped together as if they are equivalent in terms of health. Plenty of evidence links saturated fat with high cholesterol and risk of heart disease, but monounsaturated and polyunsaturated fats have the opposite effect. Although many scientists knew the distinction between the various types of fat, they felt that the average person would not understand them, and so the original pyramid was designed to send the simple message that fat was bad. The implied corollary to fat being bad was that carbohydrates were good. However, after years of study, no evidence can be shown that a diet that has 30% or fewer calories coming from fat is healthier than one with a higher level.


To further complicate matters, we have to recall the effects of the traveling forms of cholesterol—the lipoproteins. Having high levels of cholesterol trav-eling as high-density lipoproteins (HDL) has been correlated with a healthy heart, while having high levels of cholesterol traveling in the form of low-density lipoproteins (LDL) is related to high risk of heart disease. When calories from saturated fat are replaced by carbohydrates, the levels of LDL and total cholesterol decrease, but so does the level of HDL. Because the ratio of LDL to HDL does not decrease significantly, there is little health benefit. However, the increase in carbohydrate has been shown to increase fat synthesis because of increases in insulin production. When calories from unsaturated fat are replaced with calories from carbohydrates, the results are even worse. The LDL levels rise in comparison with the levels of HDL.

Figure 24.3 shows a more modern view of a food pyramid that takes into account the most recent evidence and recommendations from some nutri-tionists. Note that at the base of the pyramid is the heart and soul of good health—exercise and weight control. There is no replacement for being active and for restricting total calories when it comes to staying healthy.

The next level up shows that the good types of carbohydrates and the good forms of fats occupy a prime location. Whole-grain foods are complex car-bohydrates that are digested more slowly, so they do not have the effect of raising blood glucose and causing insulin levels to rise to the extent that refined carbohydrates like white rice and pasta do. The healthy fats come from plant oils. Vegetables and fruits still occupy an important place in this pyramid, with nuts and legumes just above them. Next are good sources of protein, such as fish, poultry, and eggs. Note that the recommendation says zero to two servings. This is a change in approach, in that the type of protein is considered important and in the fact that the guide shows that it is not necessary to eat animal protein at all. Dairy products are found high up on the new pyramid. This is because, despite the commercials that sug-gest “everybody needs milk,” there are some noted health risks in consum-ing dairy products. Some cultures that consume large quantities of dairy products have the highest incidence of heart disease, probably due to the high concentrations of saturated fatty acids in milk and butter. In addition, many adults are allergic to milk proteins, and many are unable to digest lactose. At the peak of the pyramid are the items to be eaten only sparingly: red meat and refined carbohydrates, as well as some natural carbohydrate sources, such as potatoes. In April 2006, the U.S. Department of Agriculture launched a nutrition website at www.mypyramid.gov. This service allows individuals to find information about foods and the role of physical activity in order to make choices for a healthful lifestyle. The website includes inter-active programs to help people assess their lifestyle and nutrition choices, including worksheets to record daily consumption of nutrients.

What is obesity?

Obesity is a major public-health problem in the United States. Recent figures from the National Institutes of Health show that one-third of the population is clinically obese, defined as weighing at least 20% more than their ideal weight. Artificial sweeteners have been introduced, sometimes with great controversy, to help those who wish to control their weight. Fat substitutes have come on the market more recently, again accompanied by controversy. One thing is clear: the topic will continue to be of great interest, with trade-offs between palatability and health concerns providing a driving force for finding new products.

The role of the protein leptin in the control of obesity has been established in mice, and information is just appearing concerning its effect in humans. It is known that in mice leptin is a 16-kDa protein and that it is produced by the obesity (ob) gene. Mutations in this gene lead to a deficiency of leptin, whichin turn leads to increased appetite and decreased activity, ultimately leading to weight gain. Injections of this protein into affected mice lead to decreased appetite and increased activity, with resulting weight loss. Administering leptin to leptin-deficient humans has been reported to reduce obesity; however, in clinically obese subjects, the circulating levels of leptin are often high. Some forms of obesity may be caused by a lack of sensitivity to leptin rather than a lack of leptin itself.

Leptin stimulates the oxidation of fatty acids and the uptake of glucose by muscle cells. It does so by stimulating AMP-activated protein kinase, which phosphorylates an isoform of acetyl-CoA carboxylase (ACC) in muscle cells, rendering it less active (Figure 24.4). When ACC activity is decreased, malonyl-CoA levels decrease and the mitochondria can take up and oxidize fatty acids.

Leptin also inhibits production of the mRNA for hepatic stearolyl-CoA desatu-rase, an enzyme that adds double bonds to saturated fatty acids, leading to less lipid synthesis.

Leptin also works directly on the nervous system. Both leptin and insulin  are long-term regulators of appetite. They circulate in the blood at concentrations roughly proportional to body-fat mass. They inhibit appetite by inhibiting specific neurons in the hypothalamus. Several laboratories have shown interest in using this information to develop treatments for human obe-sity.


The sources of substrates for catabolism and for anabolism are the nutri-ents derived from foodstuffs.

In humans, the choice of diet becomes important in the interest of obtain-ing enough of essential nutrients while avoiding excesses of others, such as saturated fats, where excess is known to play a role in the development of health problems.


In 1992, a food guide pyramid was published to explain nutrition basics to the public. This pyramid is currently being replaced by a newer version that recognizes the differences between various types of fats and carbo-hydrates instead of just sending the message that all fats are bad and all carbohydrates are good.


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