Relationships between Metabolic Pathways

Glycolysis and the pathways of cellular respiration do not operate in isolation from the rest of metabolism. Rather, there is an interchange, with biochemical traffic flowing both into these pathways and out of them, to and from the synthesis and breakdown of amino acids, nucleotides, fatty acids, and so forth. Carbon skeletons enter from other molecules that are broken down to release their energy (catabolism), and carbon skeletons leave to form the major macromolecular constituents of the cell (anabolism).

Catabolism and anabolism involve interconversions using carbon skeletons

A hamburger or veggiburger contains three major sources of carbon skeletons for the person who eats it: carbohydrates, mostly as starch (a polysaccharide); lipids, mostly as triglycerides (three fatty acids attached to glycerol); and proteins (polymers of amino acids).

Catabolic interconversions

Polysaccharides, lipids, and proteins can all be broken down to provide energy:

Polysaccharides are hydrolyzed to glucose. Glucose then passes through glycolysis and the citric acid cycle, where its energy is captured in NADH and ATP.

Lipids are broken down into their substituents, glycerol and fatty acids. Glycerol is converted to dihydroxyacetone phosphate, an intermediate in glycolysis, and fatty acids are converted to acetate and then acetyl CoA in the mitochondria. In both cases, further oxidation to CO2 and release of energy then occur.

Proteins are hydrolyzed to their amino acid building blocks. The 20 different amino acids feed into glycolysis or the citric acid cycle at different points.

Catabolism and anabolism are integrated

A carbon atom from a protein in your burger can end up in DNA or fat or CO2, among other fates. How does the cell “decide” which metabolic pathway to follow? With all of these possible interconversions, you might expect that the cellular concentrations of various biochemical molecules would vary widely. For example, the level of oxaloacetate in your cells might depend on what you eat (some food molecules form oxaloacetate) and whether oxaloacetate is used up (in the citric acid cycle or in forming the amino acid aspartate). Remarkably, the levels of these substances in what is called the “metabolic pool” - the sum total of all the small molecules such as metabolic intermediates in a cell - are quite constant. The cell regulates the enzymes of catabolism and anabolism so as to maintain a balance. This metabolic homeostasis gets upset only in unusual circumstances. Let’s look one such unusual circumstance: undernutrition. Glucose is an excellent source of energy. The fats and proteins can also serve as energy sources. Any one, or all three, could be used to provide the energy your body needs. In reality, things are not so simple. Proteins, for example, have essential roles in your body as enzymes and structural elements, and using them for energy might deprive you of a catalyst for a vital reaction. Polysaccharides and fats have no such catalytic roles. But polysaccharides, because they are somewhat polar, can bind a lot of water. Because they are nonpolar, fats do not bind as much water as polysaccharides do. Thus, in water, fats weigh less than polysaccharides. Also, fats are more reduced than carbohydrates (more C-H bonds as opposed to C-OH) and have more energy stored in their bonds. For these two reasons, fats are a better way for an organism to store energy than polysaccharides. It is not surprising, then, that a typical person has about one day’s worth of food energy stored as glycogen, a week’s food energy as usable proteins in blood and over a month’s food energy stored as fats. What happens if a person does not eat enough food to produce sufficient ATP and NADH for anabolism and biological activities? This situation can be the result of a deliberate decision to lose weight, but for too many people, it is forced upon them because not enough food is available. In either case, the first energy stores in the body to be used are the glycogen stores in muscle and liver cells. This doesn’t last long, and next come the fats. The level of acetyl CoA rises as fatty acids are broken down. However, a problem remains: Because fatty acids cannot get from the blood to the brain, the brain can use only glucose as its energy source. With glucose already depleted, the body must convert something else to make glucose for the brain. This gluconeogenesis uses mostly amino acids, largely from the breakdown of proteins. So, without sufficient food intake, both proteins (for glucose) and fats (for energy) are used up. After several weeks of starvation, fat stores become depleted, and the only energy source left is proteins, some of which have already been degraded to supply the brain with glucose. At this point, essential proteins, such as antibodies used to fight off infections and muscle proteins, get broken down, both for energy and for gluconeogenesis. The loss of these proteins can lead to severe illnesses.