382 



PHYSIOLOGY OF GONADS 



ketoses, but cannot be fructose as they are 

 not fermented by yeast (Mann, Leone and 

 Polge, 1956) . 



In most mammals, fructose is formed 

 mainly in the seminal vesicles (Huggins and 

 Johnson, 1933; Davies and Mann, 1947; 

 Mann, 1949; Ortiz, Price, Williams-Ashman 

 and Banks, 1956). But in the rat, the semi- 

 nal vesicles secrete little fructose, most of 

 which originates from the dorsal prostate 

 and coagulating glands (Humphrey and 

 Mann, 1949). 



Metabolic pathways for the biosynthesis 

 of seminal fructose by the accessory glands 

 have been studied extensively. From the re- 

 sults of experiments on diabetic animals, 

 Mann and Parsons (1950) concluded that 

 blood glucose was the precursor of seminal 

 fructose. The hyperglycemia resulting from 

 the administration of alloxan to rabbits was 

 accompanied by a parallel increase in the 

 fructose content of semen. Injection of in- 

 sulin into such diabetic animals led to a fall 

 in the levels of both blood glucose and semi- 

 nal fructose. Similarly, the concentration of 

 fructose in human semen was found to be 

 abnormally high in diabetic patients. Mann 

 and Lutwak-Mann (1951b) incubated 

 minced accessory gland tissue with glucose 

 and observed the formation of small amounts 

 of fructose. Cell-free extracts of bull seminal 

 vesicle showed marked phosphoglucomutase 

 and phosphohexoisomerase activity. The 

 same preparations hydrolyzed both glucose 

 6-phosphate and fructose 6-phosphate to the 

 corresponding free sugars. Slices of seminal 

 vesicle glycolyzed glucose at much greater 

 rates than fructose. On the basis of these 

 facts, Mann and Lutwak-Mann (1951a, b) 

 postulated that the conversion of glucose to 

 fructose involved an initial phosphorylation 

 of glucose to glucose 6-phosphate by hexo- 

 kinase, with adenosine triphosphate as the 

 ])hosphate donor. After enzymatic isomeri- 

 zation of glucose 6-phosphate to fructose 

 6-phosphate, the latter was dephosphoryl- 

 ated to free fructose. It was assumed that 

 any glucose formed by the dephosphoryla- 

 tion of glucose 6-phosphate was rcutilized, 

 whereas fructose was not, and hence accu- 

 mulated in the secretion. This formulation 

 is consonant with the properties of the hexo- 

 kinase of seminal vesicle (Kellerman, 19551 

 wliicli, at low sugar concentrations, phos- 



phorylates glucose at much faster rates than 

 fructose. 



It was suggested by Mann and Lutwak- 

 Mann (1951a, b) that the dephosphoryla- 

 tion of hexosemonophosphates by accessory 

 glands was catalyzed by an alkaline phos- 

 phatase which attacked the 6-phosphate es- 

 ters of both glucose and fructose. Kuhlman 

 (1954) claimed, on histochemical evidence, 

 that rat seminal vesicle contains a phos- 

 phatase specific for fructose 6-phosphate 

 which is most active in the vicinity of pH 7. 

 Kellerman (1955) stated that, although the 

 microsome-bound alkaline phosphatase of 

 guinea pig seminal vesicle hydrolyzes the 

 6-phosphate esters of glucose and fructose 

 at approximately the same rate, the mito- 

 chondria of this tissue contain a phosphatase 

 which, at pH 5.8, hydrolyzes fructose 6-phos- 

 phate ten times as rapidly as glucose 6-phos- 

 phate. However, Hers (1957a) was unable 

 to confirm these observations. 



An alternative pathway for the conver- 

 sion of glucose to fructose was suggested by 

 Williams-Ashman and Banks (1954a), who 

 found that certain fructose-secreting acces- 

 sory glands of rodents contain an enzyme, 

 ketose reductase, which catalyzes the re- 

 versible oxidation of sorbitol to fructose. 

 This enzyme attacks a number of higher 

 polyols and uses diphosphopyridine nucleo- 

 tide (DPN) as a specific hydrogen acceptor 

 (Williams-Ashman, Banks and Wolf son, 

 1957). The presence of an active ketose re- 

 ductase in male accessory sexual tissues was 

 confirmed by Hers (1956, 1957a) who dis- 

 covered another enzyme, aldose reductase, 

 which catalyzes the reduction of glucose to 

 sorbitol with dihydrotriphosphopyridine nu- 

 cleotide (TPNH) as the hydrogen donor. 

 Hers suggested that seminal fructose was 

 formed from glucose by the combined action 

 of ketose and aldose reductases, as follows: 



Glucose + TPNH + H+ ;^± Sorbitol + TPN+ 



Sorbitol + DPN+ <=^ Fructose + DPNH + H+ 



Glucose + TPNH + DPN+ 



-^ Fructose + TPN^ + DPNH 



Tliis nu'chanism for fructose biosynthesis 

 accounts for the following observations 

 ( Hers. 1957a) : (1) extracts of sheep seminal 

 vesicle convert C'^-labelcd glucose to fruc- 



