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TRANSALDOLASE

CH2-O-® Erythrose 4-phosphate

Fructose 6-phosphate

TRANSKETOLASE

Glyceraldehyde 3-phosphate

CH2-O-® Fructose 6-phosphate

Figure20-2. The pentose phosphate pathway. (®,—PO32 ; PRPP, 5-phosphoribosyl 1-pyrophosphate.)

unit comprising carbons 1 and 2 of a ketose onto the aldehyde carbon of an aldose sugar. It therefore effects the conversion of a ketose sugar into an aldose with two carbons less and simultaneously converts an aldose sugar into a ketose with two carbons more. The reaction requires Mg2+ and thiamin diphosphate (vitamin B1) as coenzyme. Thus, transketolase catalyzes the transfer of the two-carbon unit from xylulose 5-phosphate to ribose

5-phosphate, producing the seven-carbon ketose sedo-heptulose 7-phosphate and the aldose glyceraldehyde

3-phosphate. Transaldolase allows the transfer of a three-carbon dihydroxyacetone moiety (carbons 1-3) from the ketose sedoheptulose 7-phosphate onto the al-dose glyceraldehyde 3-phosphate to form the ketose fructose 6-phosphate and the four-carbon aldose erythrose

4-phosphate. In a further reaction catalyzed by transketolase, xylulose 5-phosphate donates a two-carbon unit to erythrose 4-phosphate to form fructose 6-phosphate and glyceraldehyde 3-phosphate.

In order to oxidize glucose completely to CO2 via the pentose phosphate pathway, there must be enzymes present in the tissue to convert glyceraldehyde 3-phos-phate to glucose 6-phosphate. This involves reversal of glycolysis and the gluconeogenic enzyme fructose 1,6-bisphosphatase. In tissues that lack this enzyme, glyc-eraldehyde 3-phosphate follows the normal pathway of glycolysis to pyruvate.

The Two Major Pathways for the Catabolism of Glucose Have Little in Common

Although glucose 6-phosphate is common to both pathways, the pentose phosphate pathway is markedly different from glycolysis. Oxidation utilizes NADP rather than NAD, and CO2, which is not produced in glycolysis, is a characteristic product. No ATP is generated in the pentose phosphate pathway, whereas ATP is a major product of glycolysis.

Reducing Equivalents Are Generated in Those Tissues Specializing in Reductive Syntheses

The pentose phosphate pathway is active in liver, adipose tissue, adrenal cortex, thyroid, erythrocytes, testis, and lactating mammary gland. Its activity is low in nonlactat-ing mammary gland and skeletal muscle. Those tissues in which the pathway is active use NADPH in reductive syntheses, eg, of fatty acids, steroids, amino acids via glutamate dehydrogenase, and reduced glutathione. The synthesis of glucose-6-phosphate dehydrogenase and

6-phosphogluconate dehydrogenase may also be induced by insulin during conditions associated with the "fed state" (Table 19-1), when lipogenesis increases.

Ribose Can Be Synthesized in Virtually All Tissues

Little or no ribose circulates in the bloodstream, so tissues must synthesize the ribose required for nucleotide and nucleic acid synthesis (Chapter 34). The source of ribose 5-phosphate is the pentose phosphate pathway (Figure 20-2). Muscle has only low activity of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. Nevertheless, like most other tissues, it is capable of synthesizing ribose 5-phosphate by reversal of the nonoxidative phase of the pentose phosphate pathway utilizing fructose 6-phosphate. It is not necessary to have a completely functioning pentose phosphate pathway for a tissue to synthesize ribose phosphates.

THE PENTOSE PHOSPHATE PATHWAY & GLUTATHIONE PEROXIDASE PROTECT ERYTHROCYTES AGAINST HEMOLYSIS

In erythrocytes, the pentose phosphate pathway provides NADPH for the reduction of oxidized glu-tathione catalyzed by glutathione reductase, a flavo-protein containing FAD. Reduced glutathione removes H2O2 in a reaction catalyzed by glutathione peroxi-dase, an enzyme that contains the selenium analogue of cysteine (selenocysteine) at the active site (Figure 20-3). This reaction is important, since accumulation of H2O2 may decrease the life span of the erythrocyte by causing oxidative damage to the cell membrane, leading to hemolysis.

GLUCURONATE, A PRECURSOR OF PROTEOGLYCANS & CONJUGATED GLUCURONIDES, IS A PRODUCT OF THE URONIC ACID PATHWAY

In liver, the uronic acid pathway catalyzes the conversion of glucose to glucuronic acid, ascorbic acid, and pentoses (Figure 20-4). It is also an alternative oxidative pathway for glucose, but—like the pentose phosphate pathway—it does not lead to the generation of ATP. Glucose 6-phosphate is isomerized to glucose 1-phos-phate, 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 is oxidized at carbon 6 by NAD-dependent UDPGlc de-hydrogenase in a two-step reaction to yield UDP-glu-curonate. UDP-glucuronate is the "active" form of glu-curonate for reactions involving incorporation of glucuronic acid into proteoglycans or for reactions in which substrates such as steroid hormones, bilirubin, and a number of drugs are conjugated with glucuronate for excretion in urine or bile (Figure 32-14).

Figure 20-3. Role of the pentose phosphate pathway in the glutathione peroxidase reaction of erythrocytes. (G-S-S-G, oxidized glutathione; G-SH, reduced glutathione; Se, selenium cofactor.)

Glucuronate is reduced to l-gulonate in an NADPH-dependent reaction; l-gulonate is the direct precursor of ascorbate in those animals capable of synthesizing this vitamin. In humans and other primates as well as guinea pigs, ascorbic acid cannot be synthesized because of the absence of L-gulonolactone oxidase. l-Gulonate is metabolized ultimately to d-xylulose 5-phosphate, a constituent of the pentose phosphate pathway.

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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