Evolutionary Features of the Metabolic Strategy of Mammalian Spermatozoa

The enzymatic activities of mammalian spermatozoa have kinetic properties and respond to regulation in a manner that closely resembles those of muscle cells. Although ATP-utilizing enzymes in these two types of cells are very different at a molecular level, they both produce contractile force, an activity to which the cellular metabolism is geared. This suggests that sperm's metabolic machinery is geared towards the maintenance of energy for the contractile work of motility; only minor amounts of metabolic energy appear to be consumed in other reactions, including those involved in the process of fertilization.

The preferential conversion of glucose to lactate under aerobic conditions through the Embden-Meyerhof pathway may be an important evolutionary feature of sperm, perhaps intended to minimize the accumulation of reducing equivalents in the mitochondria and the subsequent increase in oxygen radical production by the mitochondria. It is well known that sperm produce oxygen radicals, that the bulk of these radicals are produced by the mitochondria, and that oxygen radical-induced damage could result in loss of sperm motility, loss of acrosomal contents, and oxidative DNA damage [48-53] . Conversion of glucose to lactate under aerobic conditions would (1) decrease production of mitochondrial NADH and FADH-reducing equivalents by the Krebs cycle; and (2) decrease electron flow in the inner mitochondrial membrane thereby downregulating oxygen radical formation. This metabolic feature of sperm is especially important outside the protective environment of the epididymis where oxygen radical-induced damage is minimized by a lower temperature and lower pO2.

There is another evolutionary feature related to the metabolic strategy of mammalian spermatozoa worth mentioning. If we ask the question: is maximal efficiency of ATP production subordinated to maximal rate of ATP utilization in the axoneme simply because it would reduce NADH and FADH-reducing equivalents and oxygen radical production by the mitochondria? Is there another important evolutionary feature related to this strategy? The answer would be that both apply. Although ATP production by the mitochondria is far more efficient than ATP production by glycolysis in terms of moles of ATP produced per mole of glucose, should the mitochondria be the sole source of ATP for sperm, given the dimensions of the sperm flagellum and the almost lack of cytosol, diffusion of ATP to the more distal segments of the axoneme would be virtually impossible. The ATP generated in the mitochondria could only effectively diffuse to the midpiece and proximal

Fig. 10.1 Diagram that depicts the role of the glycolytic units in the axoneme in energy production in mammalian spermatozoa

region of the axoneme for appropriate maintenance of sperm motility. It has been also proposed that in order to optimize ATP utilization in the axoneme, glycolysis should be organized in the form of glycolytic units (Fig. 10.1). That is, rather than being in solution in the cytosol, given the fact that spermatozoa are highly compact cells with very little cytosol, glycolytic enzymes should be bound to cytoskeleton of the axoneme, i.e., fibrous sheath, and organized as structural and functional units that would span from hexokinase to lactate dehydrogenase. Rather than utilizing the "energy plant" of the mitochondria to produce ATP, sperm would utilize multiple "pumps" of ATP distributed along the length of the flagellum, pumping ATP at very high rates. The net ATP generated by these glycolytic units would be readily delivered to the flagellar ATPase. Recently, Young-Hwan et al. have revisited this concept of compartmentalization of glycolytic enzymes in the flagellum providing further support to this hypothesis. They found colocalization of a sperm flagellar energy carrier, designated as SFEC, and glycolytic enzymes attached to the fibrous sheath, thus supporting a growing literature that the principal piece of the flagellum is capable of generating and regulating ATP independently from mitochondrial oxi-dative phosphorylation in the midpiece. A model is proposed by these investigators by which the fibrous sheath represents a highly ordered complex, analogous to the electron transport chain of the mitochondria, in which adjacent enzymes in the gly-colytic pathway are assembled to permit efficient flux of energy substrates and products with SFEC serving to mediate energy-generating and energy-consuming processes in the distal flagellum, possibly as a nucleotide shuttle between flagellar glycolysis, protein phosphorylation, and mechanisms of motility [54].

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