208 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



TPN* 



glucose - 6- PO4- 



6- phosphogluconate 



PHOSPHOHEXOISOMERASE 



' / 



fructose - 6- PO4 



GLUCOSE - 6 - P- DEHYDROGENASE 



6- PHOSPHOGLUCONIC 



DEHYDROGENASE 



sedoheptuiose - 7-PO4 



TPN + 



TPNH 



ribulose-5-P04 



ISCMERASE /,' 

 ISOMERASE 



TRANSALDOLASE 



TRANSKETOLASE 



erythrose-4-P04 glyceraldehyde-3- PO4 ribose-5-P04 



FJG. 1 1. The hexomonophosphate pathway (pentose shunt) for glucose oxidation. 



reactions of glycolysis are reversible in cardiac muscle 

 with the aid of the Utter-Ochoa cycle, although the 

 synthesis of glycogen from pyruvate is not quantita- 

 tively important. 



Pentose pkosphale shunt. A second fate of glucose-6- 

 phosphate in cardiac muscle is the direct oxidation 

 via the TPN-dependent hexose monophosphate 

 shunt. The details of the metabolism of pentose- 

 phosphate and the proof of a pentose-hexose cycle 

 is largely due to the work of Horecker & Mehler 

 (105) and Racker (198). The first reaction of this 

 cycle is catalyzed by glucose-6-phosphate dehydro- 

 genase (named Zwischenferment by Warburg) and 

 results in the formation of 6-phosphogluconolactone 

 and TPNH followed by enzymatic hydrolysis of the 

 lactone to 6-phosphogluconic acid. A second TPN- 

 dependent dehydrogenase then converts the 6- 

 phosphogluconic acid to ribulose-5-phosphate with 

 the loss of a molecule of CO). In these two steps 

 four electrons are tiansferred to TPN+ to form two 

 molecules of TPNH which does not merge with the 

 hydrogen derived from DPN-dehydrogenase catalyzed 

 oxidations destined for transport to oxygen in the 

 sarcosome, but remains in a sarcoplasmic pool for 

 synthetic reductions required in the formation of 

 fatty acids, sterols, and other structural components 

 of heart muscle. The ribulose-5-phosphate is iso- 

 merized to ribose-5-phosphatc and xylulose-5-phos- 

 phate, and these pentose phosphates are converted 

 via transketolase (which requires thiamin pyro- 

 phosphate as a coenzyme) and transaldolase to a 

 variety of 3-, 4- and 7-carbon sugar-phosphates, and 



ultimately to fructose-6-phosphate. This provides 

 the basis for a pentose-hexose cycle with a limited 

 oxidation of glucose as shown in figure 1 1 . The over- 

 all reaction of this cycle is: 



6 glucose-6-phosphate — ► 6CO2 + 5 glucose-6-phosphate (4) 



The quantitatixe extent of this shunt varies in 

 different tissues. Clock & McLean (80) have studied 

 the distribution of the enzymes glucose-6-phosphate 

 dehvdrogenase and 6-phosphogluconate dehydro- 

 genase and found these enzymes plentiful in actively 

 synthesizing tissues such as adrenal, lactating mam- 

 mary gland, lymphatic tissues, and embryonic tissues, 

 moderate in li\er and low in i^oth skeletal and cardiac 

 muscle. A study of fetal and adult cardiac muscle by 

 Jolley and associates (113), who employed glucose-C'^ 

 labeled in various carbon atoms, revealed a significant 

 pentose shunt in rapidly growing fetal heart tissue 

 but a negligible one in adtilt pig heart homogenates. 

 The over-all glucose oxidation rate, however, was 

 3 to 4 times as high in adult as in fetal tissue. The 

 need for TPNH for synthetic leactions is apparently 

 not high in cardiac muscle. 



Glycogenesis and glycogenolysis. A third fate of glucose- 

 6-phosphate is conversion to glycogen. Although this 

 mav be viewed as a form of energy conservation (at 

 the substrate level), it is considered in this section 

 because of its important relationship to the pathways 

 of gluco.se metabolism. 



Clycogen is a highly branched polysaccharide with 

 a molecular weight of 10" to 10^, consisting of 1,4- 

 and I ,6-a-D-glucoside residues. It occurs in heart 



