Metabolic Relationships

Metabolism can be overwhelmingly complex. A large number of reactions go on at the same time and remembering how they fit together with any kind of logic is difficult. The temptation to simply memorize the individual reactions is great, but some underlying principles can help your understanding.

Energy from Glucose

Glucose is a preferred source of metabolic energy in almost all tissues. Glucose can be metabolized either aerobically or anaerobically. Although more energy is available by oxidative metabolism, some tissues can use glycolysis for a rapid burst of energy. The sources of glucose vary in different tissues.

Muscle is the largest consumer of glucose during exercise and can get glucose either from the circulation or by breaking down internal glycogen reserves. Two types of skeletal muscle exist and are distinguished by their physiological properties and their glucose metabolism.

In fast white fibers, glycolysis catabolizes glucose. The relative lack of mitochondria in these fibers causes the white appearance. The rapid breakdown of glucose by anaerobic metabolism means that ATP is made rapidly. These muscles are used in rapid, short‐duration movement and exhibit a fast twitch when electrically stimulated. The flight muscles of birds are of this type—remember that you find the white meat of a chicken on the breast.

In slow red fibers, glucose metabolism leads into the TCA cycle and metabolism is aerobic. The red appearance of these muscles comes from the large number of mitochondria in them—the iron‐containing cytochromes and myoglobin give the tissue its red appearance. The leg muscles (dark meat) of birds are of this type.

The same distinctions hold in humans. Sprinters and marathon runners have different proportions of muscle fibers, and therefore different metabolisms. Sprinters have relatively more fast white fibers, and can run very rapidly, but not for long distances. Marathon runners, on the other hand, have more slow red fibers and can carry out aerobic metabolism for very long periods of time, although they can't go as fast. Well‐trained, world‐class runners may have as much as 90 percent of their leg muscle of one type or the other, depending on their sport. Some sports, such as basketball and soccer, involve both aerobic endurance and anaerobic sprinting; these athletes tend to have both types of muscle fiber. Untrained individuals have about 50 percent of each type. The relative contributions of training and heredity to each type of metabolism remain unknown, although both play some part.

The brain relies on the circulation for nutrients and is a chief consumer of glucose. The brain uses about 15 percent of the energy required for minimal maintenance of body functions (called the basal metabolic rate). Brain tissue doesn't store energy. Instead, the brain must rely on the circulation for its fuel supply. Not all molecules can be transported across the blood‐brain barrier to be used for energy. One molecule that can cross the blood‐brain barrier is glucose, the preferred fuel source for the brain. Brain tissue can also adapt to ketone bodies such as acetoacetate as a source of fuel.

The liver is the store for and dispenser of carbohydrates to the circulation. Glycogen phosphorylase/glycogen synthetase enzyme activities control the glycogen breakdown. Hormones such as epinephrine and glucagon lead to the breakdown of glycogen to glucose‐1‐ phosphate. Phosphoglucomutase then converts glucose‐1‐phosphate to glucose‐6‐phosphate, which is then dephosphorylated to glucose as it travels to the bloodstream.

Patients who have a hereditary deficiency of glucose‐6‐phosphate phosphatase accumulate large granules of glycogen in their livers. The only fate for glucose‐6‐phosphate in these patients is conversion into glucose‐1‐phosphate and then into glycogen. All the glucose that is not directly metabolized flows “one way,” into glycogen.

Proteins and Fatty Acids

Other sources of metabolic energy include proteins and fatty acids. Muscle can use fatty acids from adipose (fat‐containing) tissues. The first reaction, in the fat globule, is the hydrolysis of triacylglycerols by lipase, to give free fatty acids and glycerol. Fatty acids move through the circulation when bound to serum albumin. Serum albumin is a general carrier of molecules in the blood, but it seems to have a specific affinity for fatty acid. After it enters the muscle, β‐ oxidation breaks down the fatty acid to Acetyl‐CoA molecules, which are then metabolized through the TCA cycle and the mitochondrial electron chain. Muscle can also use amino acids derived from proteolysis as energy sources, after their conversion to TCA cycle intermediates or pyruvate. The amino groups must be eliminated, preferably by converting them into urea in the liver. The “glucose‐alanine” cycle transports amino groups from protein breakdown to the liver. Glucose from the liver circulates to muscle and is degraded to pyruvate; pyruvate is transaminated to alanine; alanine circulates back to the liver. In the liver, the amino group is converted to urea, leaving pyruvate, which can be reconverted to glucose. No net carbon metabolism occurs during this cycle—it moves amino groups only.

The heart oxidatively metabolizes a variety of substrates, probably because it is the most essential organ in the body. The energy demands of the heart are such that it probably must rely on ATP generated in the mitochondria; not enough ATP can be made anaerobically to support these demands. The heart efficiently metabolizes fatty acids and ketone bodies and may prefer those sources of energy, even to glucose.