Correct answer = D. Calcium (Ca2+) released from the sarcoplasmic reticulum during exercise binds to the calmodulin subunit of phosphorylase kinase, thereby allosterically activating the dephosphorylated “b” form of this enzyme. The other choices are not caused by an elevation of cytosolic Ca2+ . [Note: Ca2+ also activates hepatic phosphorylase kinase b.] 1.7. Explain why the hypoglycemia seen with type Ia glycogen storage disease (glucose 6-phosphatase deficiency) is severe, whereas that seen with type VI (liver phosphorylase deficiency) is mild.
With type Ia, the liver is unable to generate free glucose either from glycogenolysis or gluconeogenesis because both processes produce glucose 6phosphate. With type VI, the liver is still able to produce free glucose from gluconeogenesis, but glycogenolysis is inhibited.
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I. OVERVIEW
Glucose is the most common monosaccharide consumed by humans, and its metabolism has already been discussed. Two other monosaccharides, fructose and galactose, also occur in significant amounts in the diet (primarily in disaccharides) and make important contributions to energy metabolism. In addition, galactose is an important component of glycosylated proteins. Figure 12.1 shows the metabolism of fructose and galactose as part of the essential pathways of energy metabolism.
II. FRUCTOSE METABOLISM
About 10% of the calories in the Western diet are supplied by fructose (~55 g/day). The major source of fructose is the disaccharide sucrose, which, when cleaved in the intestine, releases equimolar amounts of fructose and glucose. Fructose is also found as a free monosaccharide in many fruits, in honey, and in high-fructose corn syrup (typically, 55% fructose and 45% glucose), which is used to sweeten soft drinks and many foods (see p. 364). Fructose transport into cells is not insulin dependent (unlike that of glucose into certain tissues; see p. 97), and, in contrast to glucose, fructose does not promote the secretion of insulin.
A. Phosphorylation
For fructose to enter the pathways of intermediary metabolism, it must first be phosphorylated (Fig. 12.2). This can be accomplished by either hexokinase or fructokinase. Hexokinase phosphorylates glucose in most cells of the body (see p. 98), and several additional hexoses can serve as substrates for this enzyme. However, it has a low affinity (that is, a high Michaelis constant [Km]; see p. 59) for fructose. Therefore, unless the intracellular concentration of fructose becomes unusually high, the normal presence of saturating concentrations of glucose means that little fructose is phosphorylated by hexokinase. Fructokinase provides the primary mechanism for fructose phosphorylation (see Fig. 12.2). The enzyme has a low Km for fructose and a high Vmax ([maximal velocity] see p. 57). It is found in the liver (which processes most of the dietary fructose), kidneys, and the small intestine and converts fructose to fructose 1-phosphate, using ATP as the phosphate donor. [Note: These three tissues also contain aldolase B, discussed in section B.]
B. Fructose 1-phosphate cleavage