1. General Remarks:

     At one time metabolism was considered in textbooks and courses in physiology. The rapid development of biochemistry, an offshoot of physiology, has removed this subject from the domain of physiology. The sole exception is energy metabolism, which will be considered at some length here.

     The metabolism of carbohydrates, proteins, and fats will be very briefly considered here. Interested students should consult the references, especially those to textbooks of biochemistry.

2. Metabolism of Carbohydrates:

     In most of the world, carbohydrates make up the bulk of the diet. One of them, glucose, is the only substance known to be utilized by the adult brain.

     Most carbohydrates are broken down in the digestive process to glucose and other simple sugars which can be used by the animal. Thus sucrose, extracted from cane sugar, cannot be used until it is broken down by a specific digestive enzyme to glucose and fructose, which cross the intestine. Their subsequent fate, already alluded to, is conversion to glycogen in the liver. Glycogen is a storehouse for animal sugar which can be broken down when needed, supplying simple sugars to the body tissues. These may be broken down aerobically or anaerobically to yield high energy phosphate (Chapter X) or undergo other transformations (See Part 6).

     The conversion of glycogen to sugar is called glycogenolysis or glucogenesis. The process is accelerated by adrenalin (See Chapter X) and is reversed by insulin (Chapter X).

3. Metabolism of Fats:

     Fats are broken down in the digestive process. Some ingested fat crosses the intestinal wall without change, though this is usually a very small amount. Some fats are resynthesized by the intestinal mucosa immediately, although not quite as the original fat molecule. Some break down partially but in resynthesis are combined with substances that make them water soluble. These are called the phospholipids.

     Fats which are resynthesized or absorbed intact are insoluable. They travel by way of the lacteals as small particles, chloromicrons, to the thoracic duct, where they enter the circulation. These particles often give the plasma a milky appearance after a meal. They go quickly to fat depots.

     Phospholipids, which are carried in the blood rather than the lymph, have an uncertain fate.

     Depot fat is utilized when carbohydrates are in short supply. They are broken down by a lipase to fatty acids and glycerol, which are released to the blood. Evidently, most tissues except the brain are able to oxidize fatty acids and develop ATP using the energy from their oxidation.

     The total combustion of fats results in the formation of carbon dioxide. When glucose is ineffectively used, as in diabetes, or when fat is the main food, the breakdown becomes incomplete. Much of the fat breaks down to the so called "ketone bodies" which are strongly acid. Ketosis leads to acidosis, a serious complication of diabetes (See Chapter X).

4. Metabolism of Proteins:

     Almost all ingested protein is broken down to amino acids and then travels by way of the hepatic portal vein to the liver. Here an astonishing variety of things may happen. The amino acids may be reassembled in a manner more characteristic of the animal than the protein taken in. The amino group may be separated from an amino acid transferred to another acid, forming a new amino acid. The separated amino groups may be discarded as urea , their usual fate, while the residue after deamination is used to make carbohydrates or fats. More will be said about this in Chapter 25. For the present, it may be said that in the adult, non-growing animal, almost all of the protein nitrogen taken in returns as urea nitrogen.

5. Metabolism of Alcohol:

     Ethyl alcohol enters the blood without being broken down and is metabolized primarily in the liver. It is oxidized first to acetaldehyde, then to acetyl co-enzyme A. This latter compound is sometimes called "active acetate". Its interest stems from the fact that acetate, a 2 carbon acid, in combination with co-enzyme A is capable of reactions impossible for acetate alone. It should be emphasized that acetyl coenzyme A derived from alcohol does not differ in any way from any other acetyl coenzyme A. The position of the moralist that alcohol is not a food or that it is at most useful for the production of heat has no physiological basis.

     It may be mentioned in passing that hangovers have been attributed to minute amounts of acetalclehyde which have not been oxidized to acetyl co-enzyme A. Interference with this oxidation can be accomplished by a drug called tetraethyl thuram disulfide. This drug is better known and understood under one of its trade names, Antabuse.

     Antabuse has no noticeable effects by itself. However, if ethyl alcohol is given after Antabuse, it is oxidized only to acetaldehyde, and the results are, in the fullest sense, spectacular. The subject turns bright red, becomes dizzy and unstable, vomits and complains of intolerable headache, and in many cases lapses into a coma. Overall, the effects may be imagined in terms of a thousand hangovers together.

     Persons receiving Antabuse before alcohol, particularly if they have received it several times, lose some of their zest for alcoholic beverages and may even be cured of an incapacitating addiction to them. Antabuse has been employed in the treatment of chronic alcoholism with a fair amount of success. It has been suggested that this type of treatment does not touch the fundamental personality disorder which led to alcoholism in the first place. Unfortunately, there is no treatment which does (if indeed there is a fundamental personality disorder in the chronic alcoholic, a proposition open to doubt).

6. The Metabolic Pool:

     The food units which are absorbed enter the metabolic pool, where they and substances derived from them are made available for the production of more complex molecules or for the generation of energy. Any food unit can contribute to this pool, and any biological compound can be derived from it. Some compounds are more easily synthesized from the units in the pool than others. For example, proteins can be synthesized from the pool components only if there is sufficient amino nitrogen and an abundant source of compounds whose degradation will result in the formation of high energy bonds, which can be used to link amino acids. Carbohydrates are not ordinarily formed from the pool components, but they can be. Fats, including cholesterol, can always be derived from substances in the metabolic pool if these are present in excess of energy requirements.

     The synthesis of pool components into more complicated molecules and the manner in which pool components can be used to develop energy will not be considered in this textbook; these matters are better described in biochemical terms.

7. Energy Metabolism:

     Energy can be expressed in a number of ways, of which the most familiar are work and heat. Work may be described as the exertion of a force through a distance. For example, lifting a one pound weight one foot, the exertion of a one pound force through a one foot distance, is a unit of work called the foot-pound. Likewise, a kilogram-meter is a work unit which will raise one kilogram one meter. Since a kilogram is 2.2 pounds and a meter 3.28 feet, a kilogram meter is 7.23 (2.2 x 3. 28) foot-pounds.

     The following unit of work may be unfamiliar, but it is worth remembering. The standard unit of work in the metric system is the joule, which is 0. 102 kilogram-meters.

     Heat is measured in calories; a calorie is the amount of heat required to raise a cubic centimeter of water 1 ^oC. This is a very small amount of heat biologically speaking, and in biology and nutrition the kilocalorie or Calorie (note the capital C) is substituted. The Calorie is equivalent to 1000 calories.

     Joule, whose name is applied to the fundamental unit of work, showed that work could be converted to heat. The conversion factor is 1 Calorie =4190 joules. This value may take on some meaning if it is translated. 4190 joules is equal to 427.3(4190*0.102) kilogram meters. A man eating foods whose caloric value is 3000 Calories per day should be able to perform 427.3 x 3000 kilogram meters of work. Assuming a weight of 70 kilograms, this amount of food should enable him to climb 18,000 meters, almost 11 miles. This is, of course, unrealistic, because it assumes that the efficiency of conversion of food to work is 100%.

     Actually, efficiency, which may be defined as the ratio of work done to energy consumed (both in the same dimensions) is nothing like this. Many processes in the body produce no work at all in the sense of exerting a force through a distance. Muscle, which does perform this kind of work may have efficiency approaching 40%; but the whole body rarely exceeds 20% in efficiency. For example, the efficiency of a resting man is exactly zero. He metabolizes food but he does no external work. It may be instructive to make a comparison with an automobile engine. A car driven on a gasoline engine may have an efficiency of about 20-30%. When the car is stopped and the engine idles, the efficiency falls to zero. The engine uses fuel but no useful work is done. While the zero efficient, idling car can be stopped from using fuel by turning off the ignition key, the resting man must continue to use fuel just to stay alive and warm.

     Power is usually defined as work done per unit of time. In the English system, the basic unit of power is horse power, 33,000 foot-lb per minute. In the metric system one Joule/sec is the basic unit of power, the watt. The watt of power, so defined, is expressed in the same terms as the watt of energy whether electrical or mechanical and is 1/746 horse power. Due to loose usage, energy requirements and power production are often confused with each other, particularly in speaking of electrical devices which consume more energy than they develop power. To avoid this confusion in what follows, energy consumption and work production will always be specified.

     Over short periods of time (a few seconds) a man can produce work at the rate of one horse power (746 watts). Over any substantial period of time, say an hour, the ability to perform work falls to about one hundred and twenty watts, though energy may be consumed at a rate of 600 watts.

Caloric costs of work:

     These values are obviously approximations. Yet they do show that when the whole body is being moved (values below dotted line) the Calorie usage is greatly increased. The value for "lying at ease" varies somewhat, and will be discussed again in Chapter 25.

Sources of Energy:

     The basic foodstuffs when metabolized in the body yield energy as follows:

Carbohydrate	4.1 Cal / gm
Fat	9.5 Cal / gm
Proteins	4.1 Cal / gm
Alcohol	7.1 Cal / gm

     The energy generated from any of these materials is derived from the metabolic pool which all of them enter (See Part 6). It is as if all these foodstuffs formed a part of the same flame which operated the body's engines.

Caloric Balance:

     In the normal person, over any short time period there is a remarkably exact coupling between the Calorie intake and the Caloric output. For example, in the course of a month, a manual laborer may expend 100,000 Calories, and usually he will eat somewhere between 99,500 and 100,500 Calories in the same time period. It is not clear how this coupling is brought about, but there is good evidence to indicate that it is accomplished through hypothalamic centers, which regulate appetite, activity, or perhaps both.

     It seems possible that the coupling is due, at least in part, to changes in body weight. Thus, a person who has gained weight because he has temporarily eaten food in excess of his metabolic needs must expend more energy to do the same things he did before. In the case of the laborer described in the last paragraph may be illustrated by assuming that he began to eat 100,500 Calories per month regularly. The weight gain will result in increased Caloric output; so that he will now require 100,500 Calories per month and gain no more weight. If he goes back to eating 100,000 Calories per month the temporary weight gain will be reversed. The same applies to weight losses.

Body weight changes and caloric balances:

     In the body, fat is stored almost without water. Proteins and carbohydrates are associated with approximately 3 gm of water per gram of protein or carbohydrate. Thus, storage of 9 Calories as fat adds 1 gm. The picture is entirely different if gains are in carbohydrate or protein. Nine Calories gained of either means that approximately 8 grams of weight is gained. Only 2 grams are solid, but they bind 6 grams of water.

     The above explains the interesting finding often noted by people who are beginning reducing diets. A person with a daily requirement of 3000 Calories per day who goes on a diet of 2000 Calories per day is in Caloric deficit of 1000 Calories. If, as is normal, he makes up the first day's deficit with stored carbohydrate, he will lose more than 2 pounds on the first day of dieting. By the second day, however, he will begin to make up deficits with fat. Each 1000 Calorie deficit represents about 110 grams of fat and almost exactly the same weight since fat binds little water. The second day's diet results in the loss of only a quarter pound of weight.

     The opposite can also be seen. When one is in positive Caloric balance (more Calories eaten than spent), there is a tendency to weight gain. If the weight is gained as fat, it occurs at 1 gram per 9 Calories, but if the weight is stored as protein or carbohydrate, every Calorie appears as 1 gram of weight.

8. Metabolic Abnormalities:

     Most metabolic abnormalities are beyond the scope of this text, though some will be considered in Chapter 25. This entire part will be devoted to abnormalities in energy metabolism, particularly the problem of obesity.

     This condition is exceedingly common, particularly in Europe and the United States, and it shows every sign of becoming more common in countries where labor-saving devices have become available to most peop1e and entertainment has become synonymous with physical immobility (as in watching television). The prevalence of overweight in these countries is not known because height and weight tables are not very helpful, since they are based on the average population. One may well be within the "normal" range of weight according to these charts, which may mean that he is overweight to the extent which is normal for his culture.

     The onset of this disease--and it must be considered a disease--is insidious. It may result from increased food intake, reduced expenditure of energy, or both, and it takes a long time to become apparent. For example, a man of 21 who eats and uses 3000 Calories per day as a student following the habits of work, entertainment, and eating normal for his age and condition can be expected to remain at constant weight.

     A steady job and marriage may result in a subtle change. Work brings money, which brings cars, television sets, power tools and power lawn mowers. It also brings access to social circles not previously open, and cocktail parties. Marriage brings a home, regular meals, and a refrigerator for midnight snacks and beer.

     The ex-student, now on the first step toward becoming a reasonably prosperous member of society, discharges his work obligations in a 35-40 hour week. He tends to change his patterns of entertainment: participation in sports is replaced by watching sports, walks by drives, dancing and courting by more direct sexual relationships. Each of these changes saves Calories. At the same time, he eats better and more frequently and attends more cocktail parties. Cocktails, highballs, or shots of whiskey supply 130 Calories.

     For illustration, let us assume that the changed way of life results in a Calorie saving of 1000 Calories per month in work not performed and a further Calorie excess of 1000 Calories per month in extra eating and drinking. The two together, representing 2000 Calories per month, result in a very modest fat gain, 220 grams or a little less than half a pound. Assuming that the extra weight does not affect Calorie requirements, this represents only 6 pounds of fat a year. If muscle proteins are lost at the same time due to diminished activity there may be no weight change at all.

     In ten years, however, the dreadful truth may emerge. Sixty pounds of excess fat makes a fat man, even if the scales do not show all of it. Of course, in the example given, it will not be quite sixty pounds since Caloric expenditure goes up a little with body weight but a great deal of fat will have been accumulated.

     This is usually recognized by the victim as an unpleasant situation, which, he believes, calls for an emergency remedy. To suit him, there are a number of ineffective "crash" diets.

     An example of such a "crash" diet is one which calls for a high protein, low carbohydrate, high alcohol intake. At least it thinks it does. The "high protein" intake is actually expensive steak cooked rare. Interestingly, two pounds of such steak (Porterhouse), cooked rare, supplies more than the daily Caloric requirement: it contains four times as many fat Calories as protein Calories. Any unsatisfied longings, for example, for bread, are satisfied by a few drinks, say 5, for a total of 650 Calories. The dieter, who may have questioned the efficiency of the diet, by this time stops questioning anything, and allows himself to be entertained, at no particular Caloric cost, by a television set with a remote control channel changer, which permits him to watch commercials showing the antics of slim, energetic, girls drinking artificially flavored soft drinks, or liquid foods which supply measured numbers of Calories in attractive containers. The insinuation is that slenderness of the girls is associated with the food or drink advertised.

     Astonishingly enough, this diet takes off weight for a short time, though it adds to the stores of body fat. This is because certain organs, notably the brain, must have carbohydrate, and once deprived of dietary carbohydrate, one draws on his carbohydrate reserves. When these are gone, protein breaks down to enter the metabolic pool from which carbohydrate can be synthesized. Real body substance and the associated water are lost faster than fat is accumulated. The end-result is a light-weight obese person. In the course of time the diet is dropped (95% of crash diets are), and the lost carbohydrates and proteins are regained, and the fat gained during the diet remains until something effective is done to take it off. The diet described above is like a real diet still highly esteemed by some.

Management of Obesity:

     The intelligent management of obesity involves the reduction of Calorie intake, increase in Calorie output, or both. Furthermore, it involves time and patience. The obese person must change his whole way of life. He must eat less and drink less (despite invitations to cocktail parties), and he must do more despite the fact that labor-saving devices are available to him. Most important, he should recognize that it will be a long time before he will see results.

     For an example regimen, consider a man who lives three miles from work and who is accustomed to driving this distance. If he walks, he will spend 5.4 Calories per minute for 120 minutes a day for a total of about 650 Calories. If he cannot afford the time, he may choose to bicycle, which will take him from door to door faster than a car going through a built-up area to a congested parking lot, and he will still spend 420 Calories. Conservatively, such bicycling will take off forty pounds of fat per year, though the scale reading may not show it, since he will have gained muscle. If in addition, a very modest dietary restriction is imposed (say 10% less of everything he eats) a further 30 pounds of fat will be lost during a year.

     The student (who is probably lean) may wonder why so much time has been spent on the problem of obesity. The author has done so because it appears to him quite probable that because of the further development of labor-saving devices in work and home and the increased amount of leisure time (which is most easily filled by eating, drinking and watching television), Western civilization may be on the verge of a "fat explosion," one which promises to be as serious as the "population explosion." Though obesity is not a recognized cause of death as such, life insurance statistics suggest that it shortens life considerably. Taking persons 45-50 years old, each pound overweight increases the death rate 1%. This value may be of interest to persons 50 pounds overweight, who have a 50% greater chance of dying in any one year than those of normal weight.

Continue to Chapter 22.