Pentose shunt

The addition of ammonia to the variety of acids derivable from either the breakdown of glucose, glycolysis, or of the pentose shunt reaction products, ribose and NADPH, and from the citrate cycle, gives the amino acids (see Table 4.7 and Figure 4.4) Polymerisation of amino acids in cells gives proteins. In some of the amino acids sulfur and selenium can be incorporated easily. We assume NH3 was present. (Note that Se is in a coded amino acid not in Table 4.7.) Some selective metal-binding properties can be seen in Table 4.7, but amino acid carboxylates can bind all. 

While glycolysis degrades glucose to pyruvate and NADH, the pentose shunt leads from glucose to pentose and NADPH. 

Note that the strength of the correlations is increased by the fact that the citric acid pathway is today isolated in mitochondria derived from a distinct early life form and linked to both aspartate and glutamate, in which A and C are dominant amino-acid carriers, while glycolysis and the pentose shunt are cytoplasmic, where U and G are more dominant amino-acid carriers. 

Chow, C. K., and A. L. Tappel. Activities of pentose shunt and glycolytic enqrmes in lungs of ozone-exposed rats. Arch. Environ. Health 26 205-208, 1973. 

Increased activity of lung pentose shunt and glycolytic en mes decreased lactic dehydrogenase... 

The relationship of the pentose-phosphate pathway to glycolysis is shown in Figure 20-11. The steps involved in the pentose shunt are readily reversible, but there are several steps in glycolysis that are not. These are the phosphorylation steps (see Figure 20-9). Yet, there has to be a return route from pyruvate to glucose. This route is called gluconeogenesis and, in animals, takes place in... 

The beauty of the metabolic cycle through pyruvate, shown in summary in Figure 20-11, is the way it can be tapped at various points according to whether the organism requires ATP (from glycolysis), NADH (from pentose shunt), or NAD (from the lactate siding). 

A second class of ThDP-dependent enzymes, that perform the biological equivalent of the benzoin condensation reaction, interconvert sugar phosphates of different chain lengths. In the pentose shunt transketolase catalyzes the reaction shown in Scheme 10,... 

In a very imaginative piece of research Frost and coworkers have developed a plasmid-based method for synthesizing aromatic amino acids, by incorporating the genes that code for the enzymes that perform the series of conversions from D-fructose-6-phosphate to D-erythrose-4-phosphate to 3-deoxy-D-arabinoheptulosonic acid-7-phos-phate (DAHP) near each other on a plasmid that can be transformed in E. coli. The enzymes are the thiamin diphosphate-dependent enzyme transketolase in the nonoxida-tive pentose shunt and DAHP synthase. The DAHP is then converted to the cyclic dehydroquinate, a precursor to all aromatic amino acids L-Tyr, L-Phe and L-Trp165,166 (equation 27). 

TDP-dependent enzymes include transketolase, an enzyme component of the pentose shunt pathway, pyruvate dehydrogenase complex, and aKGDH a tricarboxylic acid cycle enzyme (Fig. 3). Branched-chain ketoacid dehydrogenases are also TDP-dependent. 

Figure 21 -8 Major glycolytic pathways of the erythrocyte. Substrates are in uppercase type, and enzymes are in parentheses. EMP, The Embden-Meyerhof pathway HMP hexose monophosphate pathway or pentose shunt RLC, the Rapoport-Luebering cycle ADP, adenosine diphosphate ATP, adenosine triphosphate NAD, nicotinamide-adenine dinudeotide NADH, reduced nicotinamide-adenine dinucleotide NADP, nicotinamide-adenine dinucleotide phosphate NADPH, reduced nicotinamide-adenine dinucleotide phosphate.The step from ribulose-5-phosphate, which is shown as being catalyzed by transketolase and transaldolase, is an abbreviation of this portion of the HMR...

This class of biomarkers measures actual toxic effects at the molecular, cellular and physiological levels. It is more closely related to pathological conditions (morbidity) that could lead to death. The oxidative status of cells has been proposed as a universal mechanism leading to cell dysfunction. The normal metabolism (e.g. (3-oxidation, pentose shunt pathway, immune function) produces oxidizing precursors such as hydrogen peroxide (H2O2), nitric oxide (NO) and peroxynitrite (ONOO) that are rapidly eliminated by non-enzymatic and enzymatic antioxidants to prevent tissue damage. 

Hershey et al, since 1954 (H17, H18, H19, H20) have reported on several glycolytic, pentose shunt, and Krebs cycle enzymes in human epidermis measured by Lowry s microtechniques. They have also compared enzyme activities in various structures of the skin (e.g., hair follicle, sweat gland, sebaceous gland, dermis, and epidermis), and have reported on their susceptibility to heat inactivation. 

Braun-Falco and Petzoldt (B30), Rassner (Rl), and Halprin and Ohkawara (H2) presented extensive surveys of the glycolytic, pentose shunt, and citric acid cycle enzymes in normal skin, unaffected skin of psoriatic patients, and in the lesions themselves. Figure 10 is reprinted from this work (H2) and shows the reorganization of the cellular metabolic activity made necessary by the high synthetic and mitotic rate of the tissue. 

Since the DNA concentration is about the same in psoriatic and normal epidermis (B14, M12), each cell must have a correspondingly decreased amount of structural or nonsoluble protein within it to counterbalance the increased amount of soluble protein. Within the psoriatic lesion there is more soluble protein per cell, with the ratio of carbohydrate metabolizing enzymes to the rest of these soluble proteins unaltered except for the increase in the pentose shunt activity which rises preferentially even in relation to the increased soluble protein. 

The second half of this chapter examines a pathway common to all organisms, known variously as the pentose phosphate pathway, the hexose monophosphate pathway, the phosphogluconate pathway, or the pentose shunt. The pathway provides a means by which glucose can be oxidized to generate NADPH and is the source of much of the NADPH that is needed for the biosynthesis of many biomolecules, most notably fats. We will observe the use of... 

---