Sorbitol dehydrogenase (SDH) is an enzyme in the human body. Its primary function involves converting sorbitol, a sugar alcohol, into fructose, a simple sugar. This enzymatic action is part of a metabolic route that processes sugar compounds, contributing to the body’s overall sugar metabolism.
How Sorbitol Dehydrogenase Functions
Sorbitol dehydrogenase catalyzes the reversible oxidation of sugar alcohols. Its main activity involves transforming D-sorbitol into D-fructose. This reaction requires nicotinamide adenine dinucleotide (NAD+) as a coenzyme, which converts to NADH during the process.
SDH’s function is part of the polyol pathway, also known as the sorbitol-aldose reductase pathway. This two-step process begins when aldose reductase converts glucose to sorbitol, using NADPH and converting it to NADP+. SDH then oxidizes the newly formed sorbitol to fructose.
While typically a minor route for glucose metabolism, the polyol pathway becomes more active when glucose levels are elevated. Under these conditions, the enzyme hexokinase, which normally processes glucose, can become saturated, directing excess glucose into the polyol pathway.
Where Sorbitol Dehydrogenase Acts
Sorbitol dehydrogenase is widely distributed throughout mammalian tissues. However, its concentration and activity are particularly high in certain organs. The liver contains the largest concentration of SDH, making it a primary site of action.
The enzyme is also significantly present in the seminal vesicles, ovaries, and certain nerve cells. This widespread presence indicates that SDH’s metabolic activity can influence the health and function of various bodily systems.
Sorbitol Dehydrogenase and Diabetic Complications
Elevated activity of the polyol pathway, including sorbitol dehydrogenase, contributes to complications in diabetes. In high glucose concentrations, more glucose is shunted into this pathway. This increased flux leads to sorbitol accumulation, as it is produced faster than it can be converted to fructose in some tissues.
Sorbitol accumulation within cells can cause osmotic stress, drawing water into the cells and impairing their function. The polyol pathway’s activity also consumes NADPH, a molecule important for regenerating reduced glutathione, an antioxidant. NADPH depletion reduces the cell’s antioxidant capacity, leading to oxidative stress and cellular damage.
This oxidative stress and sorbitol accumulation are implicated in various diabetic complications. For instance, diabetic neuropathy can occur due to impaired Schwann cell function caused by sorbitol buildup. Retinopathy and nephropathy are also partly attributed to this phenomenon, as these tissues can accumulate sorbitol under hyperglycemic conditions.
Sorbitol Dehydrogenase as a Diagnostic Marker
Sorbitol dehydrogenase serves as a useful biomarker in clinical diagnostics, particularly for assessing liver health. Normally, SDH levels in the blood are low. However, when liver cells are damaged, SDH is released into the bloodstream.
Elevated SDH levels in the blood indicate liver injury. This enzyme is often used with other liver enzymes, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), to provide a comprehensive assessment of liver function. Increases in SDH activity can appear within 24 hours of liver injury, making it a responsive marker for acute damage.