1.3.99.23: all-trans-retinol 13,14-reductase
This is an abbreviated version!
For detailed information about all-trans-retinol 13,14-reductase, go to the full flat file.
Word Map on EC 1.3.99.23
Reaction
Synonyms
(13,14)-all-trans-retinol saturase, 13,14-dihydroretinol saturase, all-trans-13,14-dihydroretinol saturase, all-trans-retinol:all-trans-13,14-dihydroretinol saturase, rat mammary tumor 7, retinol saturase, RetSat, RetSat A, Rmt7
ECTree
1.3.99.23 all-trans-retinol 13,14-reductaseAdvanced search results
results (
results (General Information
General Information on EC 1.3.99.23 - all-trans-retinol 13,14-reductase
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
top
GENERAL INFORMATION 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
evolution
The zebrafish RetSat enzyme exists in two isozymes, a and b, where a ist the active form and b (UniProt ID B0S6C5) is inactive
malfunction
metabolism
physiological function
additional information
malfunction
deletion of the N-terminal signal peptide prevents endoplasmic reticulum localization and lowers protein stability. When depleting RetSat in 3T3-L1 preadipocytes (a widely used cell model for adipogenesis), adipocyte differentiation is impaired. Surprisingly, supplementing these cells with all-trans-13,14-dihydroretinol failed to rescue differentiation. Differentiation of RetSat-depleted cells is rescued by adding a synthetic PPARgamma agonist, and RetSat overexpression induced PPARgamma activity during differentiation. Retsat deletion causes impaired long-term phagocytosis of apoptotic cells by peritoneal and bone marrow-derived macrophages. This effect can be rescued by providing the recombinant bridging molecule milk fat globule EGF-factor 8, whose expression is lower in RetSat-deficient macrophages. Female Retsat knockout mice are prone to develop mild systemic lupus erythematosus-like autoimmunity upon aging, and display increased spleen weights, delayed clearance of apoptotic cells, and deposition of immune complexes in organs such as the kidney. RetSat depletion in NIH3T3 cells strongly increased cell viability upon exposure to tertbutyl hydroperoxide (BHP) or H2O2. Fibroblasts depleted of RetSat are not protected from UV light or paraquat-induced stress, suggesting that loss of RetSat increases resistance selectively to damage elicited by peroxides
malfunction
liver-specific depletion of RetSat in dietary obese mice lowers hepatic and circulating TGs and normalizes hyperglycemia. Mechanistically, RetSat depletion reduces the activity of carbohydrate response element binding protein (ChREBP), a cellular hexose-phosphate sensor and inducer of lipogenesis. RetSat depletion impairs the nuclear accumulation of ChREBP. Defects upon RetSat depletion are rescued by ectopic expression of ChREBP but not by its putative enzymatic product 13,14-dihydroretinol, suggesting that RetSat affects hepatic glucose sensing independent of retinol conversion. RetSat depletion in adipocyte precursor cells impaires their adipogenic conversion in vitro, and the enzyme expression in adipose tissue is downregulated in obesity. Several glycolytic genes, including aldolase (Aldoa), phosphofructokinase, liver (Pfkl) and pyruvate kinase, liver (Pklr) are downregulated upon RetSat depletion, enzyme expression analysis
malfunction
Retsat shows reduced transcript levels in mammary adenocarcinomas and hyperplastic bladder tissue compared with normal control tissues in rats. RETSAT mutations have been identified in rare undifferentiated tongue sarcoma and malignant melanoma. These findings link low expression or mutation of RetSat to tumor development
malfunction
-
liver-specific depletion of RetSat in dietary obese mice lowers hepatic and circulating TGs and normalizes hyperglycemia. Mechanistically, RetSat depletion reduces the activity of carbohydrate response element binding protein (ChREBP), a cellular hexose-phosphate sensor and inducer of lipogenesis. RetSat depletion impairs the nuclear accumulation of ChREBP. Defects upon RetSat depletion are rescued by ectopic expression of ChREBP but not by its putative enzymatic product 13,14-dihydroretinol, suggesting that RetSat affects hepatic glucose sensing independent of retinol conversion. RetSat depletion in adipocyte precursor cells impaires their adipogenic conversion in vitro, and the enzyme expression in adipose tissue is downregulated in obesity. Several glycolytic genes, including aldolase (Aldoa), phosphofructokinase, liver (Pfkl) and pyruvate kinase, liver (Pklr) are downregulated upon RetSat depletion, enzyme expression analysis
-
metabolism
-
retinol signaling plays an important role in the establishment and maintenance of cellular phenotype in embryonic and adult vertebrate tissues. all-trans-Retinoic acid functions as the activating ligand for a family of ligand-activated transcription factors, the retinoic acid receptors, which form heterodimers with the retinoid X receptors to regulate gene transcription. Through its activation of the receptors, all-trans-retinoic acid regulates the expression of over 500 protein-coding genes
metabolism
hepatic RETSAT correlates with obesity and steatosis in humans
physiological function
-
RetSat is required for adipocyte differentiation in the 3T3-L1 cell culture model, analysis of the mechanism involved in this putative proadipogenic effect of RetSat, overview. RetSat-null mice have normal levels of retinol and retinyl palmitate in liver, serum, and adipose tissue, but, in contrast to wild-type mice, are deficient in the production of all-trans-13,14-dihydroretinol from dietary vitamin A. Despite accumulating more fat, RetSat-null mice maintained on either low-fat or high-fat diets gain weight and have similar rates of food intake as age- and gender-matched wild-type control littermates, ablation of RetSat does not result in alterations in total body weight gain but could still affect the relative composition and size of adipose stores, phenotype, overview
physiological function
cellular RetSat protein localizes primarily to the endoplasmic reticulum and catalyzes the conversion of retinol to 13,14-dihydroretinol (13,14-dhretinol), a retinoid metabolite that can act as precursor for the generation of 13,14-dihydroretinoic acid. Retinol saturase coordinates liver metabolism by regulating ChREBP activity. The oxidoreductase retinol saturase (RetSat) is involved in the development of fatty liver. Hepatic RetSat expression correlates with steatosis and serum triglycerides (TGs) in humans. Major transcriptional regulators of RetSat expression include peroxisome proliferator-activated receptor alpha (PPARalpha) and forkhead box O1 (FoxO1) in liver, and PPARgamma in adipose tissue, where RetSat's expression is robustly induced during the differentiation of precursor cells into adipocytes
physiological function
cellular RetSat protein localizes primarily to the endoplasmic reticulum and catalyzes the conversion of retinol to 13,14-dihydroretinol (13,14-dhretinol), a retinoid metabolite that can act as precursor for the generation of 13,14-dihydroretinoic acid. Retinol saturase coordinates liver metabolism by regulating ChREBP activity. The oxidoreductase retinol saturase (RetSat) is involved in the development of fatty liver. Hepatic RetSat expression correlates with steatosis and serum triglycerides (TGs) in humans. RetSat is elevated in obese mouse liver and controls lipid metabolism
physiological function
retinol saturase (RetSat) is an oxidoreductase that is expressed in metabolically active tissues and is highly regulated in conditions related to insulin resistance and type 2 diabetes. RetSat has been implicated in adipocyte differentiation, hepatic glucose and lipid metabolism, macrophage function, vision, and the generation of reactive oxygen species (ROS)
physiological function
retinol saturase (RetSat) is an oxidoreductase that is expressed in metabolically active tissues and is highly regulated in conditions related to insulin resistance and type 2 diabetes. RetSat has been implicated in adipocyte differentiation, hepatic glucose and lipid metabolism, macrophage function, vision, and the generation of reactive oxygen species (ROS). Function of RetSat and dihydroretinol in retinoid homeostasis, overview. RetSat enhances adipocyte differentiation independently of dihydroretinol formation. RetSat may drive differentiation by activating PPARgamma. RetSat is required for glucose-induced ChREBP activity and its nuclear accumulation in primary mouse hepatocytes, thus identifying RetSat as novel upstream regulator of this glucose-sensing transcription factor. RetSat regulation of carbohydrate response element-binding protein (ChREBP) is independent of dihydroretinol formation. In NIH3T3 cells RetSat is a major mediator of oxidative stress sensitivity
physiological function
retinol saturase (RetSat) is an oxidoreductase that is expressed in metabolically active tissues and is highly regulated in conditions related to insulin resistance and type 2 diabetes. RetSat has been implicated in adipocyte differentiation, hepatic glucose and lipid metabolism, macrophage function, vision, and the generation of reactive oxygen species (ROS). Function of RetSat and dihydroretinol in retinoid homeostasis, overview. RETSAT expression in liver correlates with obesity, hepatic steatosis, and the expression of carbohydrate response element-binding protein (ChREBP) target genes
physiological function
retinol saturase (RetSat) is an oxidoreductase that is expressed in metabolically active tissues and is highly regulated in conditions related to insulin resistance and type 2 diabetes. RetSat has been implicated in adipocyte differentiation, hepatic glucose and lipid metabolism, macrophage function, vision, and the generation of reactive oxygen species (ROS). The regulation of RetSat by Zfx in stem cells and its role in retinoid homeostasis may imply relevance for cell proliferation and tumorigenesis
physiological function
-
cellular RetSat protein localizes primarily to the endoplasmic reticulum and catalyzes the conversion of retinol to 13,14-dihydroretinol (13,14-dhretinol), a retinoid metabolite that can act as precursor for the generation of 13,14-dihydroretinoic acid. Retinol saturase coordinates liver metabolism by regulating ChREBP activity. The oxidoreductase retinol saturase (RetSat) is involved in the development of fatty liver. Hepatic RetSat expression correlates with steatosis and serum triglycerides (TGs) in humans. RetSat is elevated in obese mouse liver and controls lipid metabolism
-
additional information
-
RetSat deficiency leads to up-regulation of PPARgamma and PPARgamma target expression
additional information
-
the mouse pluripotent P-19 cell metabolizes retinol to all-trans-retinoic acid, analysis of expression of enzymes in the cell involved in the pathway, overview
