Harpers

166 / CHAPTER 20unit comprising carbons 1 and 2 of a ketose onto thealdehyde carbon of an aldose sugar. It therefore effectsthe conversion of a ketose sugar into an aldose with twocarbons less and simultaneously converts an aldose sugarinto a ketose with two carbons more. The reaction requiresMg 2+ and thiamin diphosphate (vitamin B 1 ) ascoenzyme. Thus, transketolase catalyzes the transfer ofthe two-carbon unit from xylulose 5-phosphate to ribose5-phosphate, producing the seven-carbon ketose sedoheptulose7-phosphate and the aldose glyceraldehyde3-phosphate. Transaldolase allows the transfer of athree-carbon dihydroxyacetone moiety (carbons 1–3)from the ketose sedoheptulose 7-phosphate onto the aldoseglyceraldehyde 3-phosphate to form the ketosefructose 6-phosphate and the four-carbon aldose erythrose4-phosphate. In a further reaction catalyzed by transketolase,xylulose 5-phosphate donates a two-carbon unitto erythrose 4-phosphate to form fructose 6-phosphateand glyceraldehyde 3-phosphate.In order to oxidize glucose completely to CO 2 viathe pentose phosphate pathway, there must be enzymespresent in the tissue to convert glyceraldehyde 3-phosphateto glucose 6-phosphate. This involves reversal ofglycolysis and the gluconeogenic enzyme fructose 1,6-bisphosphatase. In tissues that lack this enzyme, glyceraldehyde3-phosphate follows the normal pathway ofglycolysis to pyruvate.The Two Major Pathways for theCatabolism of Glucose HaveLittle in CommonAlthough glucose 6-phosphate is common to bothpathways, the pentose phosphate pathway is markedlydifferent from glycolysis. Oxidation utilizes NADPrather than NAD, and CO 2 , which is not produced inglycolysis, is a characteristic product. No ATP is generatedin the pentose phosphate pathway, whereas ATP isa major product of glycolysis.Reducing Equivalents Are Generatedin Those Tissues Specializingin Reductive SynthesesThe pentose phosphate pathway is active in liver, adiposetissue, adrenal cortex, thyroid, erythrocytes, testis, andlactating mammary gland. Its activity is low in nonlactatingmammary gland and skeletal muscle. Those tissues inwhich the pathway is active use NADPH in reductivesyntheses, eg, of fatty acids, steroids, amino acids via glutamatedehydrogenase, and reduced glutathione. Thesynthesis of glucose-6-phosphate dehydrogenase and6-phosphogluconate dehydrogenase may also be inducedby insulin during conditions associated with the “fedstate” (Table 19–1), when lipogenesis increases.Ribose Can Be Synthesized in VirtuallyAll TissuesLittle or no ribose circulates in the bloodstream, so tissuesmust synthesize the ribose required for nucleotideand nucleic acid synthesis (Chapter 34). The source ofribose 5-phosphate is the pentose phosphate pathway(Figure 20–2). Muscle has only low activity of glucose-6-phosphate dehydrogenase and 6-phosphogluconatedehydrogenase. Nevertheless, like most other tissues, itis capable of synthesizing ribose 5-phosphate by reversalof the nonoxidative phase of the pentose phosphatepathway utilizing fructose 6-phosphate. It is not necessaryto have a completely functioning pentose phosphatepathway for a tissue to synthesize ribose phosphates.THE PENTOSE PHOSPHATE PATHWAY& GLUTATHIONE PEROXIDASE PROTECTERYTHROCYTES AGAINST HEMOLYSISIn erythrocytes, the pentose phosphate pathway providesNADPH for the reduction of oxidized glutathionecatalyzed by glutathione reductase, a flavoproteincontaining FAD. Reduced glutathione removesH 2 O 2 in a reaction catalyzed by glutathione peroxidase,an enzyme that contains the selenium analogueof cysteine (selenocysteine) at the active site (Figure20–3). This reaction is important, since accumulationof H 2 O 2 may decrease the life span of the erythrocyteby causing oxidative damage to the cell membrane,leading to hemolysis.GLUCURONATE, A PRECURSOR OFPROTEOGLYCANS & CONJUGATEDGLUCURONIDES, IS A PRODUCT OFTHE URONIC ACID PATHWAYIn liver, the uronic acid pathway catalyzes the conversionof glucose to glucuronic acid, ascorbic acid, andpentoses (Figure 20–4). It is also an alternative oxidativepathway for glucose, but—like the pentose phosphatepathway—it does not lead to the generation of ATP.Glucose 6-phosphate is isomerized to glucose 1-phosphate,which then reacts with uridine triphosphate(UTP) to form uridine diphosphate glucose (UDPGlc)in a reaction catalyzed by UDPGlc pyrophosphorylase,as occurs in glycogen synthesis (Chapter 18). UDPGlc isoxidized at carbon 6 by NAD-dependent UDPGlc dehydrogenasein a two-step reaction to yield UDP-glucuronate.UDP-glucuronate is the “active” form of glucuronatefor reactions involving incorporation ofglucuronic acid into proteoglycans or for reactions inwhich substrates such as steroid hormones, bilirubin, anda number of drugs are conjugated with glucuronate forexcretion in urine or bile (Figure 32–14).