Ocular Metabolism and Disposition of 4-Hydroxy-2-nonenal

ABSTRACT

Lifelong exposure to solar radiation in the ultraviolet spectrum can result in uncontrolled levels of reactive oxygen species and consequent lipid peroxidation of cellular membranes in ocular tissues. The peroxidative degradation of lipids yields the α, β − unsaturated aldehyde, 4-hydroxy-2-nonenal (HNE) as a major product. The electrophilic nature of this molecule toward cellular nucleophiles, including protein side chains (i.e., cysteine, histidine, and lysine), deoxyribonucleic acids (i.e., guanosine), and several phospholipid head groups (i.e., ethanolamines), requires its availability to be tightly regulated. Cellular levels of HNE in the eye appear to be regulated by several biotransformation pathways, with the level of HNE metabolizing capacity varying depending on the ocular tissue of interest. It has become increasingly clear that, in the eye, these pathways are essential to normal function and the prevention of several pathologies, all of which have HNE-related etiologies. It is likely that several of these pathologies may be result, at least in part, of alterations in HNE biotransformation. This paper reviews that current literature relating to HNE metabolism in ocular structures.

Keywords :

• 4-Hydroxyl-2-nonenal
• Metabolism
• Lipid peroxidation
• Aldehyde dehydrogenase
• Alcohol dehydrogenase
• Glutathione-5-transferase