Redox Regulation and Glucose Metabolism in the Stallion Spermatozoa

Abstract

Stallion spermatozoa are cells which exhibit intense metabolic activity, where oxidative phosphorylation in the mitochondria is the primary ATP generator. However, metabolism must be viewed as a highly interconnected network of oxidation-reduction reactions that generate the energy necessary for life. An unavoidable side effect of metabolism is the generation of reactive oxygen species, leading to the evolution of sophisticated mechanisms to maintain redox homeostasis. In this paper, we provide an updated overview of glucose metabolism in stallion spermatozoa, highlighting recent evidence on the role of aerobic glycolysis in these cells, and the existence of an intracellular lactate shuttle that may help to explain the particular metabolism of the stallion spermatozoa in the context of their redox regulation.

Keywords: ROS; aerobic glycolysis; metabolism; spermatozoa; stallion.

Figure 1

Importance of the metabolism and redox reactions in the stallion spermatozoa. Enrichment of proteins matching membership terms: “metabolism” on the left and “oxidation” on the right. The outer and inner pie charts show the proportion of proteins within the background (whole proteome, outer, in black) and input (sperm proteome, inner in red) datasets, respectively. The p-values indicate that both memberships (metabolism and oxidation) are statistically significantly enriched on the lists. https://metascape.org/gp/index.html#/main/step1 (accessed on 27 July 2024).

Figure 2

Proposed mechanism of the intracellular lactate shuttle in the stallion spermatozoa. Isoforms of LDH are highly compartmentalized in the spermatozoa. LDHA and LDHC expressed in the acrosomal region (I) and tail (III), respectively, have a higher affinity for pyruvate; these isoenzymes reduce pyruvate to lactate, and the electron donor is NADH, which is oxidized to NAD⁺. NAD⁺ favors glycolysis, supporting glycolytic enzymes in the flagellum (III) and improving sperm velocity. The lactate generated is imported into the mitochondria, supporting mitochondrial function; in the mitochondria, the isoform present is LDHB (II) with a higher affinity for lactate. This is oxidized to pyruvate which feeds the TCA cycle, providing reducing equivalents and donating electrons to the ETC to generate energy to phosphorylate ADP, producing ATP.

Figure 3

(1) Excess glucose in the media triggers several damaging pathways. (2) During glycolysis, the removal of phosphate groups from glyceraldehyde 3-phosphate (GA3P) and dihydroxyacetone phosphate (DHAP) leads to the formation of reactive oxoaldehydes, such as glyoxal and methylglyoxal. These compounds, due to their highly reactive carbonyl groups, act as strong electrophiles, capable of oxidizing lipids, proteins, and DNA. Their detoxification relies on the glutathione (GSH)-dependent glyoxalase system, which consumes both GSH and NADPH. Furthermore, glyoxal can directly deactivate superoxide dismutase (SOD), further compromising antioxidant defenses. (3) Excess glucose can also be shunted into the polyol pathway, where it is reduced to sorbitol and then oxidized to fructose. These reactions consume NADPH, disrupting redox homeostasis, and NAD⁺, impacting glycolysis. Finally, mitochondrial dysfunction contributes by increasing superoxide (O₂^•− production, which inhibits glyceraldehyde 3-phosphate dehydrogenase (GAPDH), further disrupting glycolysis and leading to an accumulation of oxoaldehyde precursors, thereby exacerbating oxoaldehyde formation.