It must be obvious by now that cells have mechanisms for careful management of carbon compounds. Rather than being dead ends, most catabolic pathways contain strategic molecular intermediates (metabolites) that can be diverted into anabolic pathways. In this way, a given molecule can serve multiple purposes, and the maximum benefit can be derived from all nutrients and metabolites of the cell pool. The property of a system to integrate catabolic and anabolic pathways to improve cell efficiency is termed amphibolism.
Figure 1 demonstrates the amphibolic nature of intermediary metabolism. The pathways of glucose catabolism are an especially rich “metabolic marketplace.” The principal sites of amphibolic in teraction occur during glycolysis (glyceraldehyde-3-phosphate and pyruvic acid) and the Krebs cycle (acetyl coenzyme A and various organic acids).
Fig1. An amphibolic view of metabolism. Intermediate compounds such as pyruvic acid and acetyl coenzyme A serve multiple functions. With comparatively small modifications, these compounds can be converted into other compounds and enter a different pathway. Note that catabolism of glucose (center) furnishes numerous intermediates for anabolic pathways that synthesize amino acids, fats, nucleic acids, and carbohydrates. These building blocks can serve in further synthesis of larger molecules to construct a wide array of cell components.
Amphibolic Sources of Cellular Building Blocks
Glyceraldehyde-3-phosphate can be diverted away from glycolysis and converted into precursors for amino acid, carbohydrate, and triglyceride (fat) synthesis. (A precursor molecule is one that gives rise to a different compound.) Earlier, we noted the numerous directions that pyruvic acid catabolism can take. In terms of synthesis, pyruvate also plays a pivotal role in providing intermediates for amino acids. In the event of an inadequate glucose supply, pyruvate serves as the starting point in glucose synthesis from various metabolic intermediates, a process called gluconeogenesis.
The acetyl group that starts the Krebs cycle is another extremely versatile metabolite that can be fed into a number of syn thetic pathways. This 2-carbon fragment can be converted as a single unit into one of several amino acids, or a number of these fragments can be condensed into hydrocarbon chains that are important building blocks for fatty acid and lipid synthesis. Note that the reverse is also true: Fats can be degraded to acetyl and thereby enter the Krebs cycle via acetyl coenzyme A. This aerobic process, called beta oxidation, releases significant energy. Oxidation of a 6-carbon fatty acid with glycerol potentially yields 50 ATPs, compared with 38 for a 6-carbon sugar.
Two carbohydrate metabolites from the Krebs cycle are oxaloacetic acid and α-ketoglutaric acid—essential intermediates in the synthesis of certain amino acids. This occurs through amination, the addition of an amino group to a carbon skeleton (figure 2a). A certain core group of amino acids can then be used to synthesize others. Amino acids and carbohydrates can be interchanged through transamination as well (figure 2b).
Fig2. Reactions that produce and convert amino acids. All of the reactions require energy as ATP or NADH and specialized enzymes. (a) Through amination (the addition of an ammonium molecule [amino group]), a carbohydrate can be converted to an amino acid. (b) Through transamination (transfer of an amino group from an amino acid to a carbohydrate), metabolic intermediates can be converted to amino acids that are in low supply. (c) Through deamination (removal of an amino group), an amino acid can be converted to a useful intermediate of carbohydrate catabolism. This is how proteins are used to derive energy. Ammonium is one waste product of deamination. Note that carbohydrate structures are in brown and amino acids are in blue.
Pathways that synthesize the nitrogen bases (purines, pyrimidines), which are com ponents of DNA and RNA, originate in amino acids and so can be dependent on intermediates from the Krebs cycle as well. Because the coenzymes NAD+, NADP, FAD, and others contain purines and pyrimidines similar to the nucleic acids, their synthetic pathways are also dependent on amino acids. During times of carbohydrate deprivation, organisms can likewise convert amino acids to intermediates of the Krebs cycle by de amination (removal of an amino group) and thereby derive energy from proteins. Deamination results in the formation of nitrogen waste products such as ammonium ions or urea (figure 2c).
Formation of Macromolecules
Monosaccharides, amino acids, fatty acids, nitrogen bases, and vitamins—the building blocks that make up the various macromolecules and organelles of the cell—come from two possible sources. They can enter the cell from the outside as nutrients, or they can be synthesized through various cellular pathways. The degree to which an organism can synthesize its own building blocks (simple molecules) is determined by its genetic makeup, a factor that varies tremendously from group to group. In chapter 7, you learned that autotrophs require only CO2 as a carbon source, a few minerals to synthesize all cell substances, and no organic nutrients. Even some heterotrophic organisms (E. coli, yeasts) are so metabolically complete that they can synthesize all cellular substances from minerals and one organic carbon source such as glucose. Compare this with a strict parasite lacking or having lost significant synthetic capabilities and having to obtain most essential nutrient molecules from its host.
Whatever their source, once these building blocks are added to the metabolic pool, they are available for synthesis of polymers by the cell. The details of synthesis vary among the types of macro molecules, but all of them involve the formation of bonds by specialized enzymes and the expenditure of ATP.
Carbohydrate Biosynthesis
The role of glucose in bioenergetics is so crucial that its biosynthesis is ensured by several alternative pathways. Certain structures in the cell depend on an adequate supply of glucose as well. It is the major component of the cellulose cell walls of some eukaryotes and of certain storage granules (starch, glycogen). One of the intermediaries in glycolysis, glucose-6-P, is used to form glycogen. Mono saccharides other than glucose are important in the synthesis of bacterial cell walls. Peptidoglycan contains a linked polymer of muramic acid and glucosamine. Fructose-6-P from glycolysis is used to form these two sugars. Carbohydrates (deoxyribose, ribose) are also essential building blocks in nucleic acids. Polysaccharides are the predominant components of cell surface structures such as capsules and the glycocalyx, and they are commonly found in slime layers (dextran is an example). Remember that most polymerization reactions occur via loss of a water molecule and the input of energy.
