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
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,
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-Ionone , .
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