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Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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196<br />

Chapter | 7 The Erythrocyte: Physiology, Metabolism, and Biochemical Disorders<br />

FIGURE 7-5 Metabolic pathways <strong>of</strong> the mature erythrocyte. Abbreviations: HK, hexokinase; GPI, glucose<br />

phosphate isomerase; PFK, phosph<strong>of</strong>ructokinase; TPI, triosephosphate isomerase; GAPD, glyceraldehyde-<br />

3-phosphate dehydrogenase; PGK, phosphoglycerate kinase; MPGM, monophosphoglycerate mutase; DPGM,<br />

diphosphoglycerate mutase; PK, pyruvate kinase; G6PD, glucose-6-phosphate dehydrogenase; 6PGD,<br />

6-phosphogluconate dehydrogenase; LDH, lactate dehydrogenase; LMB, leukomethylene blue; MB, methylene<br />

blue; GR, glutathione reductase; GPx, glutathione peroxidase; TK, transketolase; TA, transaldolase; GSSG, oxidized<br />

glutathione; G6P, glucose 6-phosphate; F6P, fructose 6-phosphate; FDP, fructose 1,6-diphosphate; DHAP,<br />

dihydroxyacetone phosphate; GAP, glyceraldehyde 3-phosphate; 1,3-DPG, 1,3-diphosphoglycerate; 2,3-DPG,<br />

2,3-diphosphoglycerate; 3PG, 3-phosphoglycerate; 2PG, 2-phosphoglycerate; PEP, phosphoenolpyruvate; ADP,<br />

adenosine diphosphate; ATP, adenosine triphosphate; NAD, nicotinamide adenine dinucleotide; NADH, reduced<br />

nicotinamide adenine dinucleotide; NADP, nicotinamide adenine dinucleotide phosphate; NADPH, reduced nicotinamide<br />

adenine dinucleotide phosphate; NADPH-D, reduced nicotinamide adenine dinucleotide phosphate<br />

diaphorase; GSH, reduced glutathione; P i , inorganic phosphate; SOD, superoxide dismutase.<br />

G . Embden-Meyerh<strong>of</strong> Pathway<br />

Most <strong>of</strong> the species variations in glucose utilization appear<br />

to result from variations in EMP metabolism, with PPP<br />

metabolism being relatively constant when not stimulated<br />

by oxidants ( Harvey and Kaneko, 1976a ). In addition to the<br />

phosphorylation <strong>of</strong> glucose, one molecule <strong>of</strong> ATP is used<br />

to phosphorylate fructose 6-phosphate, and one molecule<br />

<strong>of</strong> ATP is generated for each three-carbon molecule metabolized<br />

through the phosphoglycerate kinase (PGK) and<br />

pyruvate kinase (PK) reactions ( Fig. 7-5 ). Consequently a<br />

net <strong>of</strong> two molecules <strong>of</strong> ATP is produced for each molecule<br />

<strong>of</strong> glucose metabolized to two molecules <strong>of</strong> lactate in the<br />

EMP. Because mature RBCs lack mitochondria, the EMP<br />

is the only source <strong>of</strong> ATP production in these cells.<br />

In human RBCs, reactions catalyzed by HK, phosph<strong>of</strong>ructokinase<br />

(PFK), and PK appear to be rate-limiting steps<br />

in glycolysis, because these reactions are far displaced<br />

from equilibrium ( Minakami and Yoshikawa, 1966 ). Under<br />

physiological steady-state conditions, the PFK enzyme<br />

reaction controls glycolysis through the EMP ( Rapoport,<br />

1968 ). Its activity is influenced by a variety <strong>of</strong> effectors,<br />

with ATP being the most important inhibitor and AMP and

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