BIOLOGY OF SPERMATOZOA 



76a 



The I'c'latively high glycolytic activity of 

 Imiuaii sperm was compared by MacLeod 

 1 1942) to the metabolism of certain types of 

 tumor cells (see Warburg, 1956a, b). 



The apparent toxicity of oxygen on 

 human sperm in vitro was attributed to 

 the production of hydrogen peroxide, inas- 

 much as the effect could be eliminated by 

 the addition of catalase. The enhanced res- 

 piration induced by succinate, noted above, 

 was also found to be accompanied by an 

 increase in HoOo formation. As a possible 

 mechanism of peroxide formation, the auto- 

 oxidation of a flavo-like compound was 

 suggested (MacLeod, 1943b, 1946). 



These investigations on human sperm 

 cmpiiasize the preferential utilization of 

 glycolytic substrates, under the conditions 

 of the experiments. The relative failure, 

 however, of respiratory substrates to sup- 

 port motility might well bear further scru- 

 tiny. This is particularly true in light of 

 the rapid oxidation of succinate, as shown 

 by MacLeod, and the recent report of Ter- 

 ner ( 1960) that saline suspensions of human 

 sperm oxidize both pyruvate and acetate, 

 as shown by C^^Oo production from pyru- 



ger, 1959; Hacker, 1959). In human sperm, 

 however, the rates of oxidative respiration 

 and phosphorylation are low and appear 

 to be initially metabolically suppressed. 

 Thus the oxidative inhibition is not induced 

 by high glycolytic activity itself (Crabtree 

 effect), but rather, glycolysis is favored by 

 the previous suppression of respiration. 

 The inhibition of oxidation, in turn, can 

 be attributed, if MacLeod is correct, to the 

 production of toxic amounts of hydrogen 

 peroxide, and this seems to be the relatively 

 unique feature of human sperm metabolism. 

 A plausible explanation for both the source 

 of the peroxide and the failure of respiration 

 and oxidative phosphorylation can be 

 formulated following the suggestion by 

 MacLeod (1942). Thus, it is characteristic 

 of flavoi)rotein (FAD) that, as a "pace- 

 maker" in the oxidative chain (Krebs, 

 1957), it can either transfer hydrogen atoms 

 from reduced diphosphopyridine nucleotide 

 (DPNH + ) to the cytochrome system or, 

 by auto-oxidation, noncatalytically com- 

 bine with molecular oxygen to form hydro- 

 gen peroxide (Fruton and Simmonds, 1958) 

 (see schema). 



vate-2-C^'* and acetate-1-C^^. Dinitrophenol 

 stimulated C^'*02 production from both glu- 

 cose-C^-* and pyruvate-2-C^*. 



The peculiar metabolic behavior of hu- 

 man sperm may be partially clarified l)y 

 reference to the principles of intracellular 

 regulation and alternative metabolic path- 

 ways, characteristic of other cellular and 

 subcellular systems. Of the two main types 

 of energy-producing pathways, which in a 

 sense are normally in competition (Krebs, 

 1957; Racker and Gatt, 1959 (, the process 

 of glycolytic phosphorylation in human 

 s])erm dominates oxidative phosphorylation. 

 This imbalance could be brought about by 

 the unequal distribution of such rate-limit- 

 ing substances as ADP or inorganic phos- 

 phorus (for general discussion, see Lehnin- 



Unlike most respiring cells which follow 

 the first of these alternative pathways, hu- 

 man sperm seem to be shunted off into 

 the nonphosphorylative peroxide-producing 

 route. Succinate is known to bypass DPN 

 and to donate hydrogen directly to FAD 

 (Krebs, 1957). As previously mentioned, in 

 human sperm succinate causes increases in 

 both oxygen uptake and peroxide formation 

 and a decrease in lactic acid accumulation 

 (MacLeod, 1946). But whether this repre- 

 sents a shift from glycolytic to oxidative 

 pathways or merely an inhibition of gly- 

 colysis, possibly by the poisoning of sulf- 

 hydryl-containing enzymes by excessive 

 amounts of i)eroxide (MacLeod, 1951), is 

 not known. 



Speculative as these interpretations con- 



