3,1.1.21, 220.127.116.11, 18.104.22.168, BCDP, (11Z)-Retinal, 22.214.171.124, 126.96.36.199, 4-Hydroxy-retinoic acid O4-beta-D- glucuronoside, ADHFE1, 4-Oxoretinoic acid, 188.8.131.52, ALD9A1, CYP2C19, DHA2, CRABP1, 1.13.11.-, 11-cis-Retinyl palmitate, CYP2C18, CYP3A7, 4-Hydroxy-retinol, 184.108.40.206, 220.127.116.11, ALDH2, 18.104.22.168, Retinoic acid, RDH5, RDH14, Retinol palmitate, 22.214.171.124, 126.96.36.199, 188.8.131.52, 4-Hydroxy-retinoic acid O1-beta-D- glucuronoside, CYP2B6, 184.108.40.206, CYP2A6, Xanthine oxidase, CYP1B1, CYP2C9, Retinol, DHA6, CYP2C8, DHRS4, RDH12, DHRS3, 4-Hydroxyretinoic acid, CYP2D6, CYP1A2, 220.127.116.11, UGT1A3, 18.104.22.168, 22.214.171.124, UGT1A8, Rhodopsin, RPE65, 126.96.36.199, 188.8.131.52, CRABP1, CYP1A1, rhodopsin, 184.108.40.206, 220.127.116.11, CYP3A5, CYP3A4, (11Z)-Retinol, 18.104.22.168, Retinal, AL1A7, CYP4A11, 22.214.171.124, BCDO, RDH11, beta-Apo-10'-carotenal, beta-Carotene, CYP2E1, UGT2B7, beta-Ionone, AL1A1, 3,1.1.21, 126.96.36.199
Key enzymes involved in retinoid metabolisms are alcohol and aldehyde dehydrogenases that convert retinols to aldehydes and aldehydes to carboxylic acids, respectively. The first oxidation reaction is catalyzed by a large number of enzymes from the Dehydrogenase/reductase (SDR family), and by classic medium chain Alcohol dehydrogenases .
Rhodopsin is converted by photoabsorption to metarhodopsin, and the latter is reconverted to Rhodopsin by light. It is well known that Rhodopsin can be formed from opsin only when (11Z)-Retinal is present. The photoisomerization of Retinal released during the degradation of metarhodopsin is catalyzed by an unknown isomerase is and this photoisomerization stereospecifically directed toward the formation of (11Z)-Retinal , . Retinal is also reduced in the reaction catalyzed by all -trans -retinal-specific Retinol dehydrogenases.- Retinol dehydrogenase 11 (all-trans/9-cis/11-cis) ( RDH11 ), , , Alcohol dehydrogenase, iron containing, 1 (ADHFE1 ), , Dehydrogenase/reductase (SDR family) member 3 ( DHRS3 ) , Retinol dehydrogenase 5 (11-cis/9-cis) ( RDH5 ) , , , , , Retinol dehydrogenase 12 (all-trans/9-cis/11-cis) ( RDH12 ) , , , retinol dehydrogenase 14 (all-trans/9-cis/11-cis) ( RDH14 ) , , dehydrogenase/reductase (SDR family) member (RDH14) . This dehydrogenase activity utilizes [H+] of NADH and does not require NAD + to generate Retinol. These enzymes also catalyze oxidizing (11Z)-Retinol with concomitant generation of [H] NADH to complete the cycle.
Retinol is further isomerized via inversion of the C15 prochiral methylene hydroxyl group configuration resulting in formation of (11Z)-Retinol. This reaction is catalyzed by specific isomerase , .
Retinol can also esterification to format Retinol palmitate and 11-cis-Retinyl palmitate which can be either stored in the cell or processed further . The 11-cis-Retinyl palmitate can be hydrolyzed at the rate ~20 times faster than Retinol palmitate. Human retinal epithelium contains distinct activities that hydrolyze 11-cis-Retinyl palmitate and Retinol palmitate , , .
Retinal in turn is rapidly oxidized to Retinoic acid by Xanthine dehydrogenase ( Xanthine oxidase ) , , Aldehyde dehydrogenase 2 family (mitochondrial) ( ALDH2 ) , , Aldehyde dehydrogenase 1 family, member A3 ( DHA6 ) , , Aldehyde dehydrogenase 9 family, member A1 ( ALD9A1 ), , Aldehyde dehydrogenase 1 family, member A2 ( DHA2 ) , and Aldehyde dehydrogenase family 1, subfamily A7 ( AL1A7 ) , Aldehyde dehydrogenase 1 family, member A1 ( AL1A1 ) , . Retinoic acid is metabolized to 4-Hydroxy-retinoic acid, 4-Oxo-retinoic acid and 5,6-Epoxy-retinoic acid . Oxidation of Retinoic acid to 4-Hydroxy-retinoic acid is catalyzed by cytochrome P-450 isozyme(s) Cytochrome P450, family 2, subfamily C, polypeptides 8, 9, 18, 19 ( CYP2C8, CYP2C9, CYP2C18, CYP2C19 ), Cytochrome P450, family 2, subfamily A, polypeptide 6 ( CYP2A6 ), Cytochrome P450, family 1, subfamily A, polypeptides 1 and 2 ( CYP1A1 and CYP1A2 ), Cytochrome P450, family 3, subfamily A, polypeptides 4, 5 and 7 ( CYP3A4, CYP3A5 and CYP3A7 ), Cytochrome P450, family 2, subfamily S, polypeptide 1 ( CYP2S1 ), Cytochrome P450, family 4, subfamily A, polypeptide 11 ( CYP4A11 ), Cytochrome P450, family 1, subfamily B, polypeptide 1 ( CYP1B1 ), Cytochrome P450, family 2, subfamily B, polypeptide 6 ( CYP2B6 ), Cytochrome P450, family 2, subfamily E, polypeptide 1 ( CYP2E1 ), Cytochrome P450, family 2, subfamily D, polypeptide 6 ( CYP2D6 ), Cytochrome P450, family 26, subfamily A, polypeptide 1 ( CYP26A1 ) , , , , , . The next step of Retinoic acid oxidation results in formation of 4-Oxo-retinoic acid and is also catalyzed by P450 cytochromes CYP3A4, CYP1A1, CYP2C9, CYP3A7, CYP2C8, CYP3A5 and CYP4A11 , .
Glucuronic acid can be conjugated to 4-Hydroxy-retinoic acid, which results in formation of two types of glucuronides: 4-Hydroxy-retinoic acid O1-beta-D-glucuronoside and 4-Hydroxy-retinoic acid O4beta-D-glucuronoside. These reactions are catalyzed by UDP Glucuronosyltransferase 1 family, polypeptide A8 ( UGT1A8 )  and UDP Glucuronosyltransferase 1 family, polypeptide A3 ( UGT1A3 )  to 4-Hydroxy-retinoic acid O1-beta-D-glucuronoside; and by UDP Glucuronosyltransferase 2 family, polypeptide B7 ( UGT2B7 )  and UDP-Glucuronosyltransferase 2 family, member 37 ( UDB5 )  to 4-Hydroxy-retinoic acid O4beta-D-glucuronoside.
Two key enzymes involved in carotenoid metabolism are Beta-carotene 15,15'-monooxygenase 1 ( BCDO ) and Beta-carotene oxygenase 2 ( BCDP ). The first one cleaves Beta-Carotene to form Retinal , . The second enzyme is responsible for the unconventional cleavage of Beta-Carotene to form Beta-apo-10'-carotenal and Beta-Ionone , .