Feeder Pathways for Glycolysis:- Other Monosaccharides Enter the Glycolytic Pathway at Several Points
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 of vertebrates, is phosphorylated by hexokinase:
This is a major pathway of fructose entry into glycolysis in the muscles and kidney. In the liver, however, fructose enters by a different pathway. The liver enzyme fructokinase catalyzes the phosphorylation of fructose at C-1 rather than C-6:
The fructose 1-phosphate is then cleaved to glyceraldehyde and dihydroxyacetone phosphate by fructose 1-phosphate aldolase:
Dihydroxyacetone phosphate is converted to glyceraldehyde 3-phosphate by the glycolytic enzyme triose phosphate isomerase. Glyceraldehyde is phosphorylated by ATP and triose kinase to glyceraldehyde 3-phosphate:
Thus, both products of fructose 1-phosphate hydrolysis enter the glycolytic pathway as glyceraldehyde 3 phosphate.
D-Galactose, a product of hydrolysis of the disaccharide lactose (milk sugar), passes in the blood from the intestine to the liver, where it is first phosphorylated at C-1, at the expense of ATP, by the enzyme galactokinase:
The galactose 1-phosphate is then converted to its epimer at C-4, glucose 1-phosphate, by a set of reactions in which uridine diphosphate (UDP) functions as a coenzyme-like carrier of hexose groups (Fig. 14–11). The epimerization involves first the oxidation of the C-4 OOH group to a ketone, then reduction of the ketone to an OOH, with inversion of the configuration at C-4. NAD is the cofactor for both the oxidation and the reduction.
FIGURE 14–11 Conversion of galactose to glucose 1-phosphate. The conversion proceeds through a sugar-nucleotide derivative, UDP galactose, which is formed when galactose 1-phosphate displaces glucose 1-phosphate from UDP-glucose. UDP-galactose is then converted by UDP-glucose 4-epimerase to UDP-glucose, in a reaction that in volves oxidation of C-4 (pink) by NAD+, then reduction of C-4 by NADH; the result is inversion of the configuration at C-4. The UDP glucose is recycled through another round of the same reaction. The net effect of this cycle is the conversion of galactose 1-phosphate to glucose 1-phosphate; there is no net production or consumption of UDP-galactose or UDP-glucose.
Defects in any of the three enzymes in this pathway cause galactosemia in humans. In galactokinase deficiency galactosemia, high galactose concentrations are found in blood and urine. Infants develop cataracts, caused by deposition of the galactose metabolite galactitol in the lens.
The symptoms in this disorder are relatively mild, and strict limitation of galactose in the diet greatly diminishes their severity. Transferase-deficiency galactosemia is more serious; it is characterized by poor growth in children, speech abnormality, mental deficiency, and liver dam age that may be fatal, even when galactose is withheld from the diet. Epimerase-deficiency galactosemia leads to similar symptoms, but is less severe when dietary galactose is carefully controlled. D-Mannose, released in the digestion of various poly saccharides and glycoproteins of foods, can be phosphorylated at C-6 by hexokinase:
Mannose 6-phosphate is isomerized by phosphoman nose isomerase to yield fructose 6-phosphate, an intermediate of glycolysis.
