See Figure 3-2 for an overall diagram of glucose metabolism in the lens.
Glycolysis and Hexose Monophosphate Shunt
The goal of lens metabolism is the maintenance of lens transparency. In the lens, energy production largely depends on glucose metabolism. Glucose enters the lens from the aqueous humor both by simple diffusion and by a mediated transfer process called facilitated diffusion. Most of the glucose transported into the lens is phosphorylated to glucose-6-phosphate (G6P) by the enzyme hexokinase. This reaction is 70–100 times slower than that of other enzymes involved in lens glycolysis and is, therefore, rate-limited. Once formed, G6P enters 1 of 2 metabolic pathways:
Anaerobic glycolysis. The more active of the 2 pathways, anaerobic glycolysis provides most of the high-energy phosphate bonds required for lens metabolism. In anaerobic glycolysis, substrate-linked phosphorylation of adenosine diphosphate (ADP) to adenosine triphosphate (ATP) occurs at 2 steps along the pathway from glucose metabolism to lactate. The rate-limiting step in the glycolytic pathway itself occurs at the level of the enzyme phosphofructokinase, which is regulated via feedback control by metabolic products of the glycolytic pathway. This pathway is much less efficient than the aerobic citric acid cycle (also called the tricarboxylic acid cycle or the Krebs cycle), because only 2 net molecules of ATP are produced for each glucose molecule utilized, whereas the aerobic citric acid cycle produces an additional 36 molecules of ATP from each metabolized glucose molecule (oxidative metabolism). Because of the low oxygen tension in the lens, only about 3% of the lens glucose passes through the citric acid cycle to produce ATP; however, even this low level of aerobic metabolism produces approximately 25% of the ATP of the lens.
The hexose monophosphate (HMP) shunt. Also known as the pentose phosphate pathway, the HMP shunt is the less active pathway for utilization of G6P in the lens—on average, less than 5% of lens glucose is metabolized by this route. This pathway, which is stimulated in the presence of elevated levels of glucose, is involved in the generation of NADPH or reducing power.
Figure 3-2 Simplified scheme of glucose metabolism in the lens.
(Adapted with permission from Hart WM Jr, ed. Adler’s Physiology of the Eye: Clinical Application. 9th ed. St Louis: Mosby; 1992:362.)
Excerpted from BCSC 2020-2021 series: Section 11 - Lens and Cataract. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.