The catabolism of sugars other than glucose
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Release of glucose from glycogen
The main storage carbohydrate of animal cells is glycogen, in which chains of glucose molecules—linked end-to-end, the C1 position of one glucose being linked to the C4 position of the adjacent one—are joined to each other by occasional linkages between a carbon at position 1 on one glucose and a carbon at position 6 on another. Two enzymes cooperate in releasing glucose molecules from glycogen. Glycogen phosphorylase catalyzes the splitting of the 1,4-bonds by adding the elements of phosphoric acid at the point shown by the broken arrow in [16] rather than water, as in the digestive hydrolysis of polysaccharides such as glycogen and starch. The products of [16] are glucose 1-phosphate and chains of sugar molecules shortened by one unit; the chains are degraded further by repetition of step [16]. When a bridge linking two chains, at C1 and C6 carbon atoms of adjacent glucose units, is reached, it is hydrolyzed in a reaction involving the enzyme α (1 → 6) glucosidase. After the two chains are separated, reaction [16] can occur again. The glucose 1-phosphate thus formed from glycogen or, in plants, from starch is converted to glucose 6-phosphate by phosphoglucomutase [7, 8], which catalyzes a reaction very similar to that effected in step [8] of glycolysis. Glucose 6-phosphate can then undergo further catabolism via glycolysis [2, 3, 4, 5, 6, 7, 8, 9, 10] or via either of the routes involving formation of 6-phosphogluconate [12].
Fragmentation of other sugars
Other sugars encountered in the diet are likewise transformed into products that are intermediates of central metabolic pathways. Lactose, or milk sugar, is composed of one molecule of galactose linked to one molecule of glucose. Sucrose, the common sugar of cane or beet, is made up of glucose linked to fructose. Both sucrose and lactose are hydrolyzed to glucose and fructose or galactose, respectively. Glucose is utilized as already described, but special reactions must occur before the other sugars can enter the catabolic routes. Galactose, for example, is phosphorylated in a manner analogous to step [1] of glycolysis. The reaction, catalyzed by a galactokinase, results in the formation of galactose 1-phosphate. This product is transformed to glucose 1-phosphate by a sequence of reactions requiring as a coenzyme uridine triphosphate (UTP). Fructose may also be phosphorylated in animal cells through the action of hexokinase [1], in which case fructose 6-phosphate is the product, or in liver tissue via a fructokinase that gives rise to fructose 1-phosphate [17]. ATP supplies the phosphate group in both cases.
Fructose 1-phosphate is also formed when facultative anaerobic microorganisms use fructose as a carbon source for growth; in this case, however, the source of the phosphate is phosphoenolpyruvate rather than ATP. Fructose 1-phosphate can be catabolized by one of two routes. In the liver, it is split by an aldolase enzyme [18] abundant in that tissue (but lacking in muscle); the products are dihydroxyacetone phosphate and glyceraldehyde. It will be recalled that dihydroxyacetone phosphate is an intermediate compound of glycolysis. Although glyceraldehyde is not an intermediate of glycolysis, it can be converted to one (glyceraldehyde 3-phosphate) in a reaction involving the conversion of ATP to ADP.
In many organisms other than mammals, fructose 1-phosphate does not have to undergo reaction [18] in order to enter central metabolic routes. Instead, a fructose 1-phosphate kinase, distinct from the phosphofructokinase that catalyzes step [3] of glycolysis, effects the direct conversion of fructose 1-phosphate and ATP to fructose 1,6-diphosphate and ADP.
The catabolism of lipids (fats)
Although carbohydrates are the major fuel for most organisms, fatty acids are also a very important energy source. In vertebrates at least half of the oxidative energy used by the liver, kidneys, heart muscle, and resting skeletal muscle is derived from the oxidation of fatty acids. In fasting or hibernating animals or in migrating birds, fat is virtually the sole source of energy.
Neutral fats or triglycerides, the major components of storage fats in plant and animal cells, consist of the alcohol glycerol linked to three molecules of fatty acids. Before a molecule of neutral fat can be metabolized, it must be hydrolyzed to its component parts. Hydrolysis [19] is effected by intracellular enzymes or gut enzymes, and it forms phase I of fat catabolism. Letters x, y, and z represent the number of ―CH2― groups in the fatty acid molecules.
As is apparent from [19], the three molecules of fatty acid released from the triglyceride need not be identical. A fatty acid usually contains 16 or 18 carbon atoms but may also be unsaturated—that is, containing one or more double bonds (―CH=CH―). Only the fate of saturated fatty acids—of the type CH3(CH2)nCOOH (n most commonly is an even number)—is dealt with here.
Fate of glycerol
It requires but two reactions to channel glycerol into a catabolic pathway. In a reaction catalyzed by glycerolkinase, ATP is used to phosphorylate glycerol; the products are glycerol 1-phosphate and ADP. Glycerol 1-phosphate is then oxidized to dihydroxyacetone phosphate [20], an intermediate of glycolysis. The reaction is catalyzed by either a soluble (cytoplasmic) enzyme, glycerolphosphate dehydrogenase, or a similar enzyme present in the mitochondria. In addition to their different locations, the two dehydrogenase enzymes differ in that a different coenzyme accepts the electrons removed from glycerol 1-phosphate. In the case of the cytoplasmic enzyme, NAD+ accepts the electrons (and is reduced to NADH + H+); in the case of the mitochondrial enzyme, flavin adenine dinucleotide (FAD) accepts the electrons (and is reduced to FADH2).