SBC 308: LECTURE 3-ANABOLISM AND CATABOLISM

Multienzyme Systems May Take Different Forms

The individual metabolic pathways of anabolism and catabolism consist of sequential

enzymatic steps. Several types of organization are possible. The enzymes of some

multienzyme systems may exist as physically separate, soluble entities, with diffusing

intermediates. In other instances, the enzymes of a pathway are collected to form a discrete

multienzyme complex, and the substrate is sequentially modified as it is passed along from

enzyme to enzyme. This type of organization has the advantage that intermediates are not

lost or diluted by diffusion. In a third pattern of organization, the enzymes common to a

pathway reside together as a membrane-bound system. In this case, the enzyme

participants (and perhaps the substrates as well) must diffuse in just the two dimensions of

the membrane to interact with their neighbors.

As research reveals the ultrastructural organization of the cell in ever greater detail, more

and more of the so-called soluble enzyme systems are found to be physically united into

functional complexes.

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Thus, in many (perhaps all) metabolic pathways, the consecutively acting enzymes are

associated into stable multienzyme complexes that are sometimes referred to as

metabolons, a word meaning “units of metabolism.”

How do anabolic and catabolic processes form the core of metabolic pathways

Metabolism serves two fundamentally different purposes: the generation of energy

to drive vital functions and the synthesis of biological molecules. To achieve these

ends, metabolism consists largely of two contrasting processes: catabolism and anabolism.

Catabolic pathways are characteristically energy yielding, whereas anabolic pathways are

energy requiring. Catabolism involves the oxidative degradation of complex

nutrient molecules (carbohydrates, lipids, and proteins) obtained either from the

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environment or from cellular reserves. The breakdown of these molecules by catabolism

leads to the formation of simpler molecules such as lactic acid, ethanol, carbon dioxide,

urea, or ammonia. Catabolic reactions are usually exergonic, and often the chemical energy

released is captured in the form of ATP.

Because catabolism is oxidative for the most part, part of the chemical energy may be

conserved as energy-rich electrons transferred to the coenzymes NAD+ and NADP+. These

two reduced coenzymes have very different metabolic roles: NAD reduction is part of

catabolism; NADPH oxidation is an important aspect of anabolism. The energy released

upon oxidation of NADH is coupled to the phosphorylation of ADP in aerobic cells, and so

NADH oxidation back to NAD+ serves to generate more ATP; in contrast, NADPH is the

source of the reducing power needed to drive reductive biosynthetic reactions.

Thermodynamic considerations demand that the energy necessary for biosynthesis of any

substance exceed the energy available from its catabolism. Otherwise, organisms could

achieve the status of perpetual motion machines: A few molecules of substrate whose

catabolism yielded more ATP than required for its resynthesis would allow the cell to cycle

this substance and harvest an endless supply of energy.

Anabolism Is Biosynthesis

Anabolism is a synthetic process in which the varied and complex biomolecules (proteins,

nucleic acids, polysaccharides, and lipids) are assembled from simpler precursors. Such

biosynthesis involves the formation of new covalent bonds, and an input of chemical

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energy is necessary to drive such endergonic processes. The ATP generated by catabolism

provides this energy. Furthermore, NADPH is an excellent donor of high-energy electrons

for the reductive reactions of anabolism. Despite their divergent roles, anabolism and

catabolism are interrelated in that the products of one provide the substrates of the other.

Many metabolic intermediates are shared between the two processes, and the precursors

needed by anabolic pathways are found among the products of catabolism.

Anabolism and Catabolism Are Not Mutually Exclusive

Interestingly, anabolism and catabolism occur simultaneously in the cell. The conflicting

demands of concomitant catabolism and anabolism are managed by cells in two ways. First,

the cell maintains tight and separate regulation of both catabolism and anabolism, so

metabolic needs are served in an immediate and orderly fashion. Second, competing

metabolic pathways are often localized within different cellular compartments. Isolating

opposing activities within distinct compartments, such as separate organelles, avoids

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interference between them. For example, the enzymes responsible for catabolism of fatty

acids, the fatty acid oxidation pathway, are localized within mitochondria. In contrast, fatty

acid biosynthesis takes place in the cytosol. In subsequent chapters, we shall see that the

particular molecular interactions responsible for the regulation of metabolism become

important for an understanding and appreciation of metabolic biochemistry.

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The Pathways of Catabolism Converge to a Few End Products

If we survey the catabolism of the principal energy-yielding nutrients (carbohydrates,

lipids, and proteins) in a typical heterotrophic cell, we see that the degradation of these

substances involves a succession of enzymatic reactions. In the presence of oxygen (aerobic

catabolism), these molecules are degraded ultimately to carbon dioxide, water, and

ammonia. Aerobic catabolism consists of three distinct stages. In stage 1, the nutrient

macromolecules are broken down into their respective building blocks. Despite the great

diversity of macromolecules, these building blocks represent a rather limited number of

products. Proteins yield up their 20 component amino acids, polysaccharides give rise to

carbohydrate units that are convertible to glucose, and lipids are broken down into glycerol

and fatty acids (Figure 17.7).

In stage 2, the collection of product building blocks generated in stage 1 is further degraded

to yield an even more limited set of simpler metabolic intermediates. The deamination of

amino acids leaves α -keto acid carbon skeletons. Several of these α-keto acids are citric

acid cycle intermediates and are fed directly into stage 3 catabolism via this cycle. Others

are converted either to the three-carbon α -keto acid pyruvate or to the acetyl groups of

acetyl -coenzyme A (acetyl-CoA). Glucose and the glycerol from lipids also generate

pyruvate, whereas the fatty acids are broken into two-carbon units that appear as acetyl-

CoA. Because pyruvate also gives rise to acetyl-CoA, we see that the degradation of

macromolecular nutrients converges to a common end product, acetyl-CoA (Figure 17.7).

The combustion of the acetyl groups of acetyl-CoA by the citric acid cycle and oxidative

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phosphorylation to produce CO2 and H2O represents stage 3 of catabolism. The end

products of the citric acid cycle, CO 2 and H2O, are the ultimate waste products of aerobic

catabolism.

Anabolic Pathways Diverge, Synthesizing an Astounding Variety of Biomolecules

from a Limited Set of Building Blocks

A rather limited collection of simple precursor molecules is sufficient to provide for the

biosynthesis of virtually any cellular constituent, be it protein, nucleic acid, lipid, or

polysaccharide. All of these substances are constructed from appropriate building blocks

via the pathways of anabolism. In turn, the building blocks (amino acids, nucleotides,

sugars, and fatty acids) can be generated from metabolites in the cell. For example, amino

acids can be formed by amination of the corresponding α -keto acid carbon skeletons, and

pyruvate can be converted to hexoses for poly- saccharide biosynthesis.

Amphibolic Intermediates Play Dual Roles

Certain of the central pathways of intermediary metabolism, such as the citric acid cycle,

and many metabolites of other pathways have dual purposes—they serve in both

catabolism and anabolism. This dual nature is reflected in the designation of such pathways

as amphibolic rather than solely catabolic or anabolic. In any event, in contrast to

catabolism—which converges to the common intermediate, acetyl-CoA—the pathways of

anabolism diverge from a small group of simple metabolic intermediates to yield a

spectacular variety of cellular constituents.

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Corresponding Pathways of Catabolism and Anabolism Differ in Important Ways

The anabolic pathway for synthesis of a given end product usually does not precisely match

the pathway used for catabolism of the same substance. Some of the intermediates may be

common to steps in both pathways, but different enzymatic reactions and unique

metabolites characterize other steps. A good example of these differences is found in a

comparison of the catabolism of glucose to pyruvic acid by the pathway of glycolysis and

the biosynthesis of glucose from pyruvate by the pathway called gluconeogenesis. The

glycolytic pathway from glucose to pyruvate consists of 10 enzymes. Although it may seem

efficient for glucose synthesis from pyruvate to proceed by a reversal of all 10 steps,

gluconeogenesis uses only seven of the glycolytic enzymes in reverse, replacing those

remaining with four enzymes specific to glucose biosynthesis. In similar fashion, the

pathway responsible for degrading proteins to amino acids differs from the protein

synthesis system, and the oxidative degradation of fatty acids to two-carbon acetyl-CoA

groups does not follow the same reaction path as the biosynthesis of fatty acids from

acetyl-CoA.

FIGURE 17.7 The three stages of catabolism. Stage 1: Proteins, polysaccharides, and
lipids are broken down into their component building blocks, which are relatively
few in number. Stage 2: The various building blocks are degraded into the common
product, the acetyl groups of acetyl-CoA. Stage 3: Catabolism converges to three
principal end products: water, carbon dioxide, and ammonia.

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