In addition to glucose, many other carbohydrates ultimately enter the glycolytic
pathway to undergo energy-yielding degradation. The most significant are the
storage polysaccharides glycogen and starch, the disaccharides maltose, lactose,
trehalose, and sucrose, and the monosaccharides fructose, mannose, and
galactose. We shall now consider the pathways by which these carbohydrates can
enter glycolysis.
Glycogen and Starch Are Degraded by Phosphorolysis
The glucose units of the outer branches of glycogen and starch gain entrance into the glycolytic pathway through the sequential action of two enzymes: glycogen phosphorylase (or the similar starch phosphorylase in plants) and phosphoglucomutase. Glycogen phosphorylase catalyzes the reaction in which an (α1→4) glycosidic linkage joining two glucose residues in glycogen undergoes attack by inorganic phosphate, removing the terminal glucose residue as α-D--glucose-1-phosphate (Fig. 14-11). This phosphorolysis reaction that occurs during intracellular mobilization of glycogen stores is different from the hydrolysis of glycosidic bonds by amylase during intestinal degradation of glycogen or starch; in phosphorolysis, some of the energy of the glycosidic bond is preserved in the formation of the phosphate ester, glucose-1-phosphate.
Pyridoxal phosphate is an essential cofactor in the glycogen phosphorylase reaction; its phosphate group acts as a general acid catalyst, promoting attack by Pi on the glycosidic bond. A quite different role of pyridoxal phosphate as a cofactor in amino acid metabolism will be described in detail in Chapter 17.
Glycogen phosphorylase (or starch phosphorylase) acts repetitively on the nonreducing ends of glycogen (or amylopectin) branches until it reaches a point four glucose residues away from an (α1→6) branch point (see Fig. 11-15). Here the action of glycogen or starch phosphorylase stops. Further degradation can occur only after the action of a "debranching enzyme," oligo (α1→6) to (α1→4) glucantransferase, which catalyzes two successive reactions that remove branches (Fig. 14-12).
Glucose-1-phosphate, the end product of the glycogen and starch phosphorylase reactions, is converted into glucose-6-phosphate by phosphoglucomutase, which catalyzes the reversible reaction
In the muscles and kidney of vertebrates this is a major pathway. In the
liver, however, fructose gains entry into glycolysis by a different pathway. The
liver enzyme fructokinase catalyzes the phosphorylation of
fructose, not at C-6, but at C-l:
The fructose-1-phosphate is then cleaved to form glyceraldehyde and
dihydroxyacetone phosphate by fructose-1-phosphate
aldolase.Dihydroxyacetone phosphate is converted into glyceraldehyde-3phosphate by the
glycolytic enzyme triose phosphate isomerase. Glyceraldehyde is phosphorylated
by ATP and triose kinase to glyceraldehyde-3-phosphate:
Glycogen and Starch Are Degraded by Phosphorolysis
The glucose units of the outer branches of glycogen and starch gain entrance into the glycolytic pathway through the sequential action of two enzymes: glycogen phosphorylase (or the similar starch phosphorylase in plants) and phosphoglucomutase. Glycogen phosphorylase catalyzes the reaction in which an (α1→4) glycosidic linkage joining two glucose residues in glycogen undergoes attack by inorganic phosphate, removing the terminal glucose residue as α-D--glucose-1-phosphate (Fig. 14-11). This phosphorolysis reaction that occurs during intracellular mobilization of glycogen stores is different from the hydrolysis of glycosidic bonds by amylase during intestinal degradation of glycogen or starch; in phosphorolysis, some of the energy of the glycosidic bond is preserved in the formation of the phosphate ester, glucose-1-phosphate.
Pyridoxal phosphate is an essential cofactor in the glycogen phosphorylase reaction; its phosphate group acts as a general acid catalyst, promoting attack by Pi on the glycosidic bond. A quite different role of pyridoxal phosphate as a cofactor in amino acid metabolism will be described in detail in Chapter 17.
Glycogen phosphorylase (or starch phosphorylase) acts repetitively on the nonreducing ends of glycogen (or amylopectin) branches until it reaches a point four glucose residues away from an (α1→6) branch point (see Fig. 11-15). Here the action of glycogen or starch phosphorylase stops. Further degradation can occur only after the action of a "debranching enzyme," oligo (α1→6) to (α1→4) glucantransferase, which catalyzes two successive reactions that remove branches (Fig. 14-12).
Glucose-1-phosphate, the end product of the glycogen and starch phosphorylase reactions, is converted into glucose-6-phosphate by phosphoglucomutase, which catalyzes the reversible reaction
Glucose-1-phosphate ![]()
__________
glucose-6-phosphate
Phosphoglucomutase requires as a cofactor
glucose-1,6-bisphosphate; its role is analogous to that of
2,3-bisphosphoglycerate in the reaction catalyzed by phosphoglycerate mutase
(Fig. 14-6). Phosphoglucomutase, like phosphoglycerate mutase, cycles between a
phosphorylated and nonphosphorylated form. In phosphoglucomutase, however, it is
the hydroxyl group of a Ser residue in the active site that is transiently
phosphorylated in the catalytic cycle.Other Monosaccharides Can Enter the Glycolytic Pathway
In most organisms, hexoses other than glucose can undergo glycolysis after conversion to a phosphorylated derivative. D-Fructose, present in free form in many fruits and formed by hydrolysis of sucrose in the small intestine, can be phosphorylated by hexokinase, which acts on a number of different hexoses:| Fructose + ATP | _______Mg2+ |
fructose-6-phosphate + ADP |
| Fructose + ATP | ________Mg2+ |
fructose-1-phosphate + ADP |
| Glyceraldehyde + ATP | ___________Mg2+ |
glyceraldehyde-3-phosphate + ADP |
|
Thus both products of fructose hydrolysis enter the glycolytic pathway as
glyceraldehyde- 3-phosphate. D-Galactose, derived by hydrolysis of the disaccharide lactose (milk sugar), is first phosphorylated at C-1 at the expense of ATP by the enzyme galactokinase:
Galactose + ATP__________
The galactose-1-phosphate is then converted into its epimer at C-4,
glucose-1-phosphate, by a set of reactions in which uridine diphosphate (UDP)
functions as a coenzymelike carrier of hexose groups (Fig. 14-13).There are several human genetic diseases in which galactose metabolism is affected. In the most common form of galactosemia, the enzyme UDP-glucose : galactose-1-phosphate uridylyltransferase (Fig. 14-13) is genetically defective, preventing the overall conversion of galactose into glucose. Other forms of galactosemia result when either galactokinase or UDP-glucose-4-epimerase is genetically defective. D-Mannose, which arises from the digestion of various polysaccharides and glycoproteins present in foods, can be phosphorylated at C-6 by hexokinase:
Dietary Disaccharides Are Hydrolyzed to MonosaccharidesDisaccharides cannot directly enter the glycolytic pathway; indeed they cannot enter cells without first being hydrolyzed to monosaccharides extracellularly. In vertebrates, ingested disaccharides must first be hydrolyzed by enzymes attached to the outer surface of the epithelial cells lining the small intestine (Fig. 14-14), to yield their monosaccharide units:
Lactose intolerance is a condition, common among adults of most human races except Northern Europeans and some Africans, in which the ingestion of milk or other foods containing lactose leads to abdominal cramps and diarrhea. Lactose intolerance is due to the disappearance after childhood of most or all of the lactase activity of the intestinal cells (Fig. 14-14b), so that lactose cannot be completely digested and absorbed. Lactose not absorbed in the small intestine is converted by bacteria in the large intestine into toxic products that cause the symptoms of the condition. In those parts of the world where lactose intolerance is prevalent, milk is simply not used as a food by adults. Milk products digested with lactase are commercially available in some countries as an alternative to excluding milk products from the diet. In certain diseases of humans, several or all of the intestinal disaccharidases are missing because of genetic defects or dietary factors, resulting in digestive disturbances triggered by disaccharides in the diet (Fig. 14-14b). Altering the diet to reduce disaccharide content sometimes alleviates the symptoms of these defects. Figure 14-15 summarizes the feeder pathways that funnel hexoses, disaccharides, and polysaccharides into the central glycolytic pathway. |
