After studying this chapter, you should be able to:
- Describe the pentose phosphate pathway and its roles as a source of NADPH and in the synthesis of ribose for nucleotide synthesis.
- Describe the uronic acid pathway and its importance for synthesis of glucuronic acid for conjugation reactions and (in animals for which it is not a vitamin) vitamin C.
- Describe and explain the consequences of large intakes of fructose.
- Describe the synthesis and physiological importance of galactose.
- Explain the consequences of genetic defects of glucose 6-phosphate dehydrogenase deficiency (favism), the uronic acid pathway (essential pentosuria), and fructose and galactose metabolism.
The pentose phosphate pathway is an alternative route for the metabolism of glucose. It does not lead to formation of ATP but has two major functions: (1) the formation of NADPH for synthesis of fatty acids and steroids, and maintaining reduced glutathione for antioxidant activity, and (2) the synthesis of ribose for nucleotide and nucleic acid formation. Glucose, fructose, and galactose are the main hexoses absorbed from the gastrointestinal tract, derived from dietary starch, sucrose, and lactose, respectively. Fructose and galactose can be converted to glucose, mainly in the liver.
Genetic deficiency of glucose 6-phosphate dehydrogenase, the first enzyme of the pentose phosphate pathway, is a major cause of acute hemolysis of red blood cells, resulting in hemolytic anemia. Glucuronic acid is synthesized from glucose via the uronic acid pathway, of minor quantitative importance, but of major significance for the conjugation and excretion of metabolites and foreign chemicals (xenobiotics) as glucuronides. A deficiency in the pathway leads to the condition of essential pentosuria. The lack of one enzyme of the pathway (gulonolactone oxidase) in primates and some other animals explains why ascorbic acid (vitamin C) is a dietary requirement for humans but not most other mammals. Deficiencies in the enzymes of fructose and galactose metabolism lead to metabolic diseases such as essential fructosuria, hereditary fructose intolerance, and galactosemia.
The pentose phosphate pathway (hexose monophosphate shunt) is a more complex pathway than glycolysis (Figure 21–1). Three molecules of glucose 6-phosphate give rise to three molecules of CO2 and three 5-carbon sugars. These are rearranged to regenerate two molecules of glucose 6-phosphate and one molecule of the glycolytic intermediate, glyceraldehyde 3-phosphate. Since two molecules of glyceraldehyde 3-phosphate can regenerate glucose 6-phosphate, the pathway can account for the complete oxidation of glucose.
Flow chart of pentose phosphate pathway and its connections with the pathway of glycolysis. The full pathway, as indicated, consists of three interconnected cycles in which glucose 6-phosphate is both substrate and end-product. The reactions above the broken line are nonreversible, whereas all reactions under that line are freely reversible apart from that catalyzed by fructose 1,6-bisphosphatase.
Like glycolysis, the enzymes of the pentose phosphate pathway are cytosolic. Unlike glycolysis, oxidation ...