The Biochemical Basis of Vitamin A₃ Production in Arthropod Vision

Abstract

Metazoan photochemistry involves cis-trans isomerization of a retinylidene chromophore bound to G protein coupled receptors. Successful production of chromophore is critical for photoreceptor production and survival. For chromophore production, animals have to choose from more than 600 naturally occurring carotenoids and process them by oxidative cleavage and geometric isomerization of double bonds. Vertebrates employ three carotenoid cleavage oxygenases to tailor the carotenoid precursor in the synthesis of 11-cis-retinal (vitamin A1). Lepidoptera (butterfly and moth) possess only one such enzyme, NinaB, which faces the challenge to catalyze these reactions in unison to produce 11-cis-3-hydroxy-retinal (vitamin A3). We here showed that key to this multitasking is a bipartite substrate recognition site that conveys regio- and stereo-selectivity for double bond processing. One side performed the specific C11, C12 cis-isomerization and preferentially binds 3-OH-β-ionone rings sites. The other side maintained a trans configuration in the resulting product and preferentially binds non-canonical ionone ring sites. Concurrent binding of carotenoids containing two cyclohexyl rings to both domains is required for specific oxidative cleavage at position C15, C15’ of the substrate. The unique reaction sequence follows a dioxygenase mechanism with a carbocation/radical intermediate. This ingenious quality control system guarantees 11-cis-3-hydroxy-retinal production, the essential retinoid for insect (vitamin A3) vision.

Chronic exposure to imidacloprid or thiamethoxam neonicotinoid causes oxidative damages and alters carotenoid-retinoid levels in caged honey bees (Apis mellifera)

“…Despite recent evidence of RA implications in the development of insects, few studies addressed the link between RA and the carotenoid-retinoid metabolism. So far, NinaB, an isomeroxygenase that combines carotene oxygenase and retinoid isomerase functions, was found in several insect species 40 and appears to use many carotenoids such as α/β-carotene, β-cryptoxanthin, lutein and zeaxanthin as substrates in order to produce various proportions of RALD isomers 40 , 41 . In D. melanogaster , short chain dehydrogenases (SDRs) were shown to be biochemically similar to the human Rdh12 42 .…”

Conserved chemosensory proteins in the proboscis and eyes of Lepidoptera

“…Using these models of the four CSPs we then performed docking simulations with β-carotene, 3-hydroxyretinol and 3-hydroxyretinal (the visual pigments used by insect instead of retinol and retinal used by vertebrates 43) and found that all three molecules can fit well inside the binding pockets.…”

RPE65 has an additional function as the lutein to meso -zeaxanthin isomerase in the vertebrate eye

“…In other species, a single enzyme can perform the functions of BCO1, BCO2, and RPE65. Arthropods encode a single carotenoid cleavage enzyme, NinaB, that performs the functions of all three BCO family members (34). Carotenoid cleavage enzymes in lower organisms have a range of substrate specificities.…”