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The Mechanism of Rhodopsin Synthesis

1951; National Academy of Sciences; Volume: 37; Issue: 2 Linguagem: Inglês

10.1073/pnas.37.2.69

1091-6490

Ruth Hubbard, George Wald,

Neuroscience and Neuropharmacology Research

We have recently demonstrated the synthesis of rhodopsin from vitamin A, and opsin (rhodopsin-protein) in retinal homogenates and aqueous retinal extracts.' This process was shown to be aided by supplementation with homogenates of the pigment layers of the eye-the pigment epithelium and choroid-and with cozymase (DPN).A mechanism was proposed for rhodopsin synthesis, based upon the following considerations.(1) Vitamin A, is in equilibrium with retinene, through the retinene reductase system, in which cozymase functions as coenzyme.2The equilibrium lies far over toward the side of reduction (vitamin A,), but can be dis- placed in the oxidative direction by the use of a retinene-trapping reagent such as hydroxylamine, which condenses spontaneously with retinene, to form retinene, oxime.In this process the endergonic oxidation of vitamin A, to retinene, is coupled with the exergonic trapping reaction.'(2) Retinene, condenses spontaneously also with opsin to form rhodopsin.3This exergonic process can serve as a retinene-trapping reaction in the retina.Rhodopsin may therefore be synthesized by the oxidation of vitamin A, to retinene1 by the retinene reductase system, coupled with the condensation of retinene, with opsin to form rhodopsin.'These reactions are summarized in the following diagram: Rhodopsin retinene 1 light reductase DPN-H2 + opsin Vitamin A1, 7 Retinene1 DPN + hydroxylamine Retinene1 oxime