Adipose tissue pentose phosphate pathway

Figure 25-7. Metabolism of adipose tissue. Hormone-sensitive lipase is activated by ACTH, TSH, glucagon, epinephrine, norepinephrine, and vasopressin and inhibited by insulin, prostaglandin E, and nicotinic acid. Details of the formation of glycerol 3-phosphate from intermediates of glycolysis are shown in Figure 24-2. (PPP, pentose phosphate pathway TG, triacylglycerol FFA, free fatty acids VLDL, very low density lipoprotein.)...

Some mammalian cells have the ability to metabolize glucose 6-phosphate in a pathway that involves the production of C3, C4, C5, C6, and C7 sugars. This process also yields the reduced coenzyme, NADPH, which is oxidized in the biosynthesis of fatty acids and steroids (Chap. 13). Consequently, this metabolic pathway is of major importance in those cells involved in fatty acid and steroid production, such as the liver, lactating mammary gland, adrenal cortex, and adipose tissue. The pentose phosphate pathway, which does not require oxygen and which occurs in the cytoplasm of these cells, has two other names the phosphogluconate pathway (after the first product in the pathway) and the hexose monophosphate shunt (since the end products of the pathway can reenter glycolysis). 

Mode 3. Much more NADPII than ribose 5-phosphate is required. For example, adipose tissue requires a high level of NADPH for the synthesis of fatty acids (Table 20.4). In this case, glucose 6-phosphate is completely oxidi i to CO>. Three groups of reactions are active in this situation. First, the oxidative phase of the pentose phosphate pathway forms two molecules ot NADPH and one molecule of ribose S-phosphate. Then, ribose 5-phosphate... 

The pentose phosphate pathway is most active in tissues involved in cholesterol and fatty acid biosynthesis. These two processes require abundant NADPH. Thus the liver, which is the site of cholesterol synthesis and a major site for fatty acid biosynthesis, and adipose (fat) tissue, where active fatty acid synthesis also occurs, have very high levels of pentose phosphate pathway enzymes. 

The pentose phosphate pathway is an alternative pathway for glucose degradation that is particularly abundant in the liver and adipose tissue. It provides the cell with a source of NADPH to serve as a reducing agent for bios)mthetic reactions. It also provides ribose-5-phosphate for nucleotide synthesis and erythrose-4-phosphate for bios)mthesis of the amino acids tryptophan, t)rrosine, and phenylalanine. 

Unlike reduced NAD, reduced NADP is not used during oxidative phosphorylation to produce ATP, and the main fimction of the pentose phosphate pathway is to provide reduced NADP for tissues that have a specific demand for it, particularly those actively synthesising fatty acids. Almost one-third of the glucose metabolised by the liver may follow this pathway, and this figme may be exceeded in adipose tissue. Reduced NADP can be converted to reduced NAD via an energy-linked transhydrogenase and thus serve indirectly as a source of ATP. 

Tissues which are more active in the synthesis of lipids than nucleotides require NADPH rather than ribose moieties. In such tissues, e.g. adipose tissue, the ribose 5-phosphate enters a series of sugar interconversion reactions which connect the pentose phosphate pathway with glycolysis and gluconeogenesis. These interconversion reactions constitute the non-oxidative phase of the pathway (Figure 11.14) and since oxidation is not involved, NADPH is not produced. Two enzymes catalyse the important reactions transketolase which contains thiamin diphosphate (Figure 12.3a) as its prosthetic group and transaldolase. Both enzymes function in the transfer of carbon units transketolase transfers two-carbon units and transaldolase transfers three-carbon units. The transfer always occurs from a ketose donor to an aldose acceptor. The interconversion sequence requires the oxidative phase to operate three times, i.e. three molecules of glucose 6-phosphate yield three molecules of ribulose 5-phosphate. 

FIGURE 11.14 The non-oxidative phase of the pentose phosphate pathway in adipose tissue... 

---