9.2: Metabolism

As said earlier, metabolism includes the energy- releasing reactions that break apart molecules, and the energy-requiring reactions that put molecules together. When the energy-providing nutrients (fat, carbohydrate, protein) are broken apart, two forms of energy are released—heat and ATP (Chap. 3). ATP is used for things like muscle action and the synthesis of enzymes, hormones, and tissues.

Metabolism is controlled by many substances, including enzymes, coenzymes, minerals, and hormones. Enzymes catalyze the reactions, enabling them to occur. They play a key role in directing metabolism, since each reaction requires its own special enzyme. Coenzymes work with enzymes (cooperate with enzymes) usually by carrying a key substance that’s made or used in a reaction. Coenzymes aren’t as choosy as enzymes. Each typically works with many enzymes, whereas specific enzymes are needed for specific reactions.

Minerals also are essential coworkers with enzymes, e.g., calcium is needed in a blood clotting reaction (Chap. 7). Hormones help direct and coordinate metabolism by carrying “messages” to various parts of the body, e.g., sex hormones appearing at puberty start reactions that lead to a boy’s deepening voice and a girl’s developing breasts.

B-vitamins

There are eight B-vitamins: thiamin, riboflavin, niacin, folate, biotin, pantothenic acid, vitamin B₆, and vitamin B₁₂. All are water-soluble. Some of their functions, food sources, and symptoms of deficiency and toxicity are given in Appendix A-5.

Each of the B-vitamins is an essential part of a different coenzyme. Coenzymes act as carriers between reactions, much like delivery trucks that continually ferry lumber between lumber mills and construction sites. The B-vitamins riboflavin and niacin, for example, are parts of coenzymes that ferry hydrogen atoms.

Because coenzymes play a crucial role in the metabolism of all living things, all the B-vitamins, except B₁₂, are found in both plants and animals. B₁₂ isn’t found in plants; its coenzyme isn’t needed for a plant’s metabolism.

Plants and many microbes don’t need an outside source of B-vitamins because they make them. It could be said that we eat their coenzymes and use the B-vitamin portions to make our own coenzymes. The cow, for example, gets its riboflavin from that made by bacteria that live in the cow’s rumen. We, in turn, ingest that riboflavin when we eat beef or drink milk.

Niacin-Tryptophan-Pellagra Connection

The body can make the B-vitamin niacin from tryptophan, an essential amino acid. We don’t need niacin in our diet if we get enough tryptophan. In other words, to become niacin deficient, the diet has to be low in both niacin and tryptophan. This helps explain the distribution of the disease pellagra in the early 1900s (see Chap.1).

Niacin deficiency causes pellagra, which was especially prevalent in the South, where the diet commonly was based on corn products, with very little added meat, eggs, or milk. Niacin in corn happens to be tightly bound to other substances in corn, hampering its absorption from the digestive tract. In addition, corn is particularly low in the amino acid tryptophan (Figure 11.1). Meat, eggs, and milk are low in niacin but are good sources of tryptophan. Thus, meat, eggs, or milk can prevent pellagra because we can make niacin from the tryptophan in these foods.

The diet in Mexico was also based on corn products with little added meat, eggs, or milk, but pellagra wasn’t as prevalent as in the southern United States. One explanation is that in making tortillas, corn is first soaked in a solution of lime (calcium oxide). This makes niacin in corn easier to absorb, thus providing more niacin (and more calcium) than untreated corn. Also, coffee was more widely consumed, and coffee contains niacin.

Energy-Releasing Reactions

When energy-providing nutrients are broken down, energy is released. There are two kinds of energy-releasing reactions—those that do not require oxygen (anaerobic) and those that do (aerobic). Figure 9.2 outlines these energy-releasing reactions, indicating where glucose, fatty acids, amino acids, and alcohol come in.

Figure 9.2: Energy-Releasing Reactions

Let’s begin with glucose, our most handy fuel. Starch—the main source of energy for the world’s population—is absorbed from the intestine as glucose. We always carry glucose in our blood, and store glucose as glycogen in liver and muscle for quick release of glucose.

Anaerobic Energy Production (Glycolysis)

Glucose (a 6-carbon molecule) is broken down to pyruvate (3-carbons) in a set of reactions called glycolysis [from the Greek glycos (sugar) and lysis (to break apart)]. The reactions take place in the cell cytoplasm and are anaerobic [an(without) aerobic(air)], meaning that oxygen isn’t used.

Only a small amount of the potential energy in glucose is released here, but is important because this ATP is made without oxygen. In weightlifting, for example, the muscle contractions squeeze the capillaries in the muscle, temporarily limiting its oxygen supply. ATP generated from anaerobic metabolism of glucose fuels the muscle action needed for the lift and hold. Glucose is conveniently stored as glycogen in muscle cells.

Pyruvate (the end-product of glycolysis) normally proceeds to a set of aerobic (oxygen-requiring) reactions in the mitochondria (Figure 9.2). But the reactions can’t proceed if oxygen is scarce, as in endurance events. In these cases, pyruvate is converted to lactic acid, which helps sustain anaerobic ATP production a bit longer.*

When cows are killed, glycolysis continues briefly, using glucose from muscle glycogen. But oxygen is unavailable (breathing and blood circulation have stopped), so lactic acid accumulates. This added acidity of the carcass improves meat’s appearance and texture, and there’s less spoilage because the acidity hampers microbial growth. If muscle glycogen is depleted before slaughter (e.g., stress-induced muscle tension), all this doesn’t happen. There are thus commercial as well as humane reasons for treating animals well before slaughter.

Glycolysis is synonymous with fermentation. Both use the same reactions to break down glucose into pyruvate. But some organisms such as yeast convert the pyruvate to alcohol. The yeast takes the sugar in grape juice and, by glycolysis, makes ATP for itself and wine for us. In converting pyruvate to alcohol, carbon dioxide (CO₂) is released. Trapping this CO₂ gives the fizz of champagne and beer.

^{*Converting pyruvate to lactic acid frees a coenzyme (NAD) needed in glycolysis. NAD (nicotinamide adenine dinucleotide) is a niacin-containing coenzyme that ferries hydrogen (H) atoms. Pyruvate takes H from NADH to become lactic acid. This frees NAD. In the trucks-carrying-lumber analogy: H is lumber; glycolysis needs empty trucks (NAD). In everyday activities, oxygen isn’t limiting. H is easily unloaded by aerobic metabolism; making lactic acid isn’t necessary.}

Aerobic Energy Production

The next set of reactions† is aerobic (uses oxygen) and takes place in mitochondria, the site of all oxygen-requiring reactions.** Pyruvate (a 3-carbon molecule) goes from the cytoplasm (anaerobic) to the mitochondria (aerobic), and is broken down to acetate (2-carbons).†† Acetate breaks down to carbon dioxide (1-carbon), completing the breakdown of energy-providing nutrients.

Lots of energy is made in mitochondria. The use of oxygen enables a net production of 38 ATP molecules from 1 glucose molecule. Without oxygen, there’s a net production of only 2 ATP. Clearly, mitochondria enable cells to make a lot more energy.

Mitochondria are thought to be former microbes that hundreds of millions of years ago permanently infected our cells. They do, in fact, have their own DNA. Without mitochondria, cells can’t use oxygen and are limited to the ATP made by glycolysis. Cells “infected” with mitochondria would have had a huge advantage in evolution. When the supply of nutrients was limited (the usual situation), cells with mitochondria could make much more ATP than other cells. The extra ATP could fuel greater growth, movement, and synthesis of complex molecules.

Aerobic is a familiar word in reference to exercise. It’s called aerobic because continuous and sustained exercise (e.g., running) requires fatty acids as fuel, and ATP production from fatty acids is completely dependent on oxygen. In other words, the use of fatty acids for energy is entirely aerobic and takes place exclusively in mitochondria. Aerobic exercise enhances the cardiovascular system’s ability to circulate more oxygen to exercising muscles, thus promoting cardiovascular fitness.

Fatty acids are broken down to acetate* and then to carbon dioxide (Figure 9.2). Because energy is stored in the body mainly as fat (triglycerides), fatty acids are the main source of energy whenever cells need to call on substantial energy reserves (perhaps when a person is on a weight-loss diet, or running a marathon).

Amino acids can also be used as fuel, but aren’t the best source (Chap. 10). The nitrogen-containing (amino) part is removed. The remaining structure is converted to pyruvate† and enters the energy-releasing set of reactions (Figure 9.2). When fat stores are depleted (e.g., by starvation), amino acids from protein in our organs and muscles are used as a source of energy. When this happens, the body “wastes away.”

^{†This set is called the citric acid cycle, TCA (tricarboxylic acid) cycle, or Krebs cycle. Hans Krebs discovered these reactions and shared a Nobel Prize in 1953 with Fritz Lipmann.
**The poisonous gas hydrogen cyanide blocks oxygen-requiring reactions in mitochondria. It’s been used in the gas chamber for capital punishment, and is made by dropping cyanide pellets into acid.
††Acetate is carried by Coenzyme A, which contains the B-vitamin pantothenic acid. In the trucks-carrying-lumber analogy, the lumber is acetate. Franz Lipmann discovered Coenzyme A and its role in metabolism and shared a 1953 Nobel Prize with Hans Kreb.
*For his part in this discovery, Feodor Lynen won a Nobel Prize in 1964.
†Some amino acids are converted to acetate, depending on the amino acid’s structure.}

Athletic Performance

Athletes are useful examples in explaining anaerobic and aerobic energy production. Athletes push ATP production to its limits. Athletics can be roughly grouped according to whether glucose (strength-and-power events) or fatty acid (endurance events) is the main fuel.

Strength-and-power events (e.g., weight-lifting, gymnastics, sprints, shot put) mainly use ATP generated anaerobically from glycolysis. Oxygen isn’t a limiting factor—the event is short. The reactions of glycolysis are very fast and make ATP much faster for “bursts of energy.”

Don’t confuse speed of ATP production with the total amount made from one molecule of glucose. Most of the energy released from glucose comes from the aerobic reactions of metabolism, but these are rather slow. In contrast, glycolysis breaks down many glucose molecules to make lots of ATP quickly.

Recall that ATP isn’t stored, but is made as needed. A sprinter doesn’t gather ATP while anticipating the starting gun. The ATP to fuel that sprint is made during the sprint itself. It needs to be made fast!

Types of muscle cells: It follows that athletes with a greater capacity for glycolysis will be more successful in events that call for a short and intense burst of energy. Muscle cells differ in their anaerobic and aerobic capability, and can be roughly divided into two types: white (fast-twitch) fibers and red (slow-twitch) fibers. (Muscle cells are often called fibers, because they’re long and cylindrical.) Muscles are made of both white and red fibers; most of us have both in about equal amounts.

White fibers are geared for glycolysis (e.g., have more glycolysis enzymes), allowing them to contract (twitch) rapidly. Red fibers are geared toward the slower, aerobic production of energy; they have more fat and mitochondria. Red fibers are also rich in myoglobin, which is similar to the hemoglobin in red blood cells.

Both myoglobin and hemoglobin are proteins that contain heme (which contains iron) and carry oxygen. Myoglobin in muscle holds oxygen that can be used when oxygen from blood is restricted (as when muscle contractions squeeze the capillaries). Muscles of seals and whales are exceptionally rich in myoglobin, to provide oxygen to generate ATP when they dive and swim underwater.

Muscle fibers in the relevant muscles of elite strength-and-power athletes are more than 70% white, whereas those of elite endurance athletes are more than 70% red. These proportions seem to be genetic. (Quarter horses and greyhounds are bred for speed. Fibers in their leg muscles are about 95% white.) For athletes intending to break world records, heredity could well be destiny. Training, however, can markedly enhance the aerobic (and possibly the anaerobic) capacity of both types of fibers.

The iron-containing heme in myoglobin (and hemoglobin) is red, giving a reddish color to muscles rich in red fibers. People are familiar with these muscle fibers in their preference for either dark or white meat in the Thanksgiving turkey.

The dark meat of the turkey leg is mostly red fibers, and is thus well adapted to turkeys running around (endurance). The white breast meat is mostly white fibers, needed for the burst of power that turkeys use to flap their wings in making a fast move. (In contrast, the breast of migratory birds is dark meat, needed for the endurance of long, nonstop flights.) As a food, this makes dark turkey meat higher in fat and iron than white meat.*

The flesh of fish is mostly white fibers. Survival depends a lot on a fish’s ability to make quick movements—to catch prey, or avoid being caught. Fish don’t need much power to cruise the waters; for this, fish have thin bands of red fibers just under their skin and/or near their fins. (The flesh of salmon is actually white, but looks pink, because of pigments from insects and such that salmon feed on.)

Oxygen delivery: Endurance athletes need a steady production of ATP over a long time—more ATP than glycogen (glucose) stores can provide. But even the leanest athlete has more than enough body fat to fuel a marathon. Oxygen is needed to “burn” fat, so the amount of oxygen available to the muscles is what becomes limiting.

Endurance athletes work for cardiovascular fitness (to deliver oxygen and remove carbon dioxide and lactic acid as fast as possible), and they train to enhance the aerobic capacity of their muscles. Also, as discussed in Chapter 7, some endurance athletes attempt to boost the amount of red blood cells (i.e., the oxygen-carrying capacity) in their blood.

Glucose supply: Aerobic metabolism is sluggish when glucose is scarce. In other words, a muscle doesn’t “burn” fatty acids as well if it runs out of glucose.† Endurance athletes often use carbohydrate-loading to temporarily increase glycogen (the storage form of glucose) in the relevant muscles.** The extra supply of glycogen delays muscle fatigue.

Endurance athletes also work to “spare” the use of glucose so it won’t run out as fast. Drinking carbohydrate-containing beverages during events of more than 90 minutes helps (Chap. 4). Caffeine can also help, because it promotes the use of fatty acids as fuel, thus sparing the use of glucose.

Local acidity in muscle, caused by lactic acid production, can cause muscle fatigue and can be a limiting factor in events like the 400- and 800-meter races—“all-­out” events of 1 to 2 minutes. In “soda-loading,” sodium bicarbonate (baking soda) is consumed prior to the event. Bicarbonate is alkaline in pH and counters the acidity of the lactic acid build-up.*** Taken at the right time and dosage, soda loading has been shown to improve running times by as much as 1½ seconds in a 400 meter race and 3 seconds in an 800-meter race—times that can mean the difference between first and last place. But a common side effect is “urgent diarrhea” which, of course, can deter performance if it occurs at the wrong time.

^{*Looking for good sources of iron in the diet, we can make a visual appraisal of the heme-iron content of meat (Chap. 7). Myoglobin in muscle has the red iron-containing heme, so the redder meats generally have more heme iron. Beef liver has more iron than hamburger, which has more iron than chicken or fish. Whale and seal meat is very dark and rich in iron because it’s so rich in myoglobin.
†Fatty acids are released from triglycerides, which are composed of 3 fatty acids attached to a backbone of glycerol (see Figure 5.2). Glycerol is a 3-carbon sugar, which can be made into glucose. Smart combination!
**About a week before competition, athletes train hard and then taper training, resting on the day before the event. For 3 days before the event, they eat a high-carbohydrate diet. The intense exercise depletes the muscles of glycogen. Upon repletion with a high-carb diet, there’s a rebound effect—glycogen stores are temporarily raised to higher-than-normal levels in time for the event.
***In the digestive tract, sodium bicarbonate from the pancreas neutralizes the acid material coming from the stomach (Chap. 6).​​​​​​​}