Correct answer = C. The girl is deficient in galactokinase and is unable to appropriately phosphorylate galactose. Galactose accumulates in the blood (and urine). In the lens of the eye, galactose is reduced by aldose reductase to galactitol, a sugar alcohol, which causes osmotic effects that result in cataract formation. Deficiency of galactose 1-phosphate uridylyltransferase also results in cataracts but is characterized by liver damage and neurologic effects. Fructokinase deficiency is a benign condition. Aldolase B deficiency is severe, with effects on several tissues. Cataracts are not typically seen.
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I. OVERVIEW
The pentose phosphate pathway (or, hexose monophosphate shunt) occurs in the cytosol. It includes an irreversible oxidative phase, followed by a series of reversible sugar–phosphate interconversions (Fig. 13.1). In the oxidative phase, carbon 1 of a glucose 6-phosphate molecule is released as carbon dioxide (CO2), and one pentose sugar-phosphate plus two reduced nicotinamide adenine dinucleotide phosphates (NADPH) are produced. The rate and direction of the reversible reactions are determined by the supply of and demand for intermediates of the pathway. The pentose phosphate pathway provides a major portion of the body’s NADPH, which functions as a biochemical reductant. It also produces ribose 5-phosphate, required for nucleotide biosynthesis (see p. 293), and provides a mechanism for the conversion of pentose sugars to triose and hexose intermediates of glycolysis. No ATP is directly consumed or produced in the pathway.
II. IRREVERSIBLE OXIDATIVE REACTIONS
The oxidative portion of the pentose phosphate pathway consists of three irreversible reactions that lead to the formation of ribulose 5-phosphate, CO2, and two molecules of NADPH for each molecule of glucose 6-phosphate oxidized (Fig. 13.2). This portion of the pathway is particularly important in the liver, lactating mammary glands, and adipose tissue for the NADPH-dependent biosynthesis of fatty acids (see p. 186); in the testes, ovaries, placenta, and adrenal cortex for the NADPH-dependent biosynthesis of steroid hormones (see p. 237); and in red blood cells (RBC) for the NADPH-dependent reduction of glutathione (see p. 148).
A. Glucose 6-phosphate dehydrogenation
Glucose 6-phosphate dehydrogenase (G6PD) catalyzes the oxidation of glucose 6-phosphate to 6-phosphogluconolactone as the coenzyme NADP+ gets reduced to NADPH. This initial reaction is the committed, rate-limiting, and regulated step of the pathway. NADPH is a potent competitive inhibitor of G6PD, and the ratio of NADPH/NADP+ is sufficiently high to substantially inhibit the enzyme under most metabolic conditions. However, with increased demand for NADPH, the ratio of NADPH/NADP+ decreases, and flux through the pathway increases in response to the enhanced activity of G6PD. [Note: Insulin upregulates expression of the gene for G6PD, and flux through the pathway increases in the absorptive state (see p. 323).]