Short-chain dehydrogenase/reductases: endocrine and redox control in metabolism
🧪 lmctl-orchestrated review — written by an orchestrated team of AI agents, grounded in 1,347 papers from lmmol's literature graph. Citations link to their source on PubMed.
| Protein | Papers |
|---|---|
| 11-beta-hydroxysteroid dehydrogenase 1 | 29 |
| 3-hydroxyacyl-CoA dehydrogenase type-2 | 29 |
| WW domain-containing oxidoreductase | 28 |
| Peroxisomal multifunctional enzyme type 2 | 28 |
| 11-beta-hydroxysteroid dehydrogenase type 2 | 27 |
| Alcohol dehydrogenase | 26 |
| 17-beta-hydroxysteroid dehydrogenase type 1 | 24 |
| 15-hydroxyprostaglandin dehydrogenase [NAD(+)] | 22 |
The short-chain dehydrogenase/reductase (SDR) superfamily is a compact catalytic scaffold with broad physiological reach, especially in hormone conversion, lipid processing, and stress-linked redox control [1][2][3]. Across taxa, conserved motifs are redeployed in distinct settings, so shared fold does not imply shared biology without expression context and compartmentalization [4][5][6].
1. Core biology and fold-level unification
A defining feature is how a conserved redox grammar yields different pathway outcomes. Classic work in steroid systems shows that tissue specificity and partner context can turn similar catalytic modules into very different physiological controls [7][8][6]. Even within the same superfamily, substrate preference and redox directionality are often rewired around disease-relevant tissue states, making localization as important as chemistry [9][10].
2. What has shifted in recent literature
Recent years foregrounded two themes: mechanistic nuance and translational utility. Genetic stratification studies identify HSD17B13 effects on liver outcomes, while retinoid and neurobiology links continue to reposition this family beyond classic endocrinology [3][11][12]. The same lane also highlights how oxidative cofactor balance and membrane context shape redox output in disease states, so interpretation now needs pathway-aware reading rather than isolated motif matching [13].
3. How to interpret this topic in lmmol
For this topic, prioritize neighborhoods where SDR chemistry co-locates with endocrine and neuro-metabolic outcomes, rather than high-degree housekeeping references. Strong candidates combine mechanism-heavy nodes with phenotypic directionality: steroid converters, retinoid-linked branches, and lipid stress modules [4][9][6].
References
- McDonald J.H., Kreitman M. Adaptive protein evolution at the Adh locus in Drosophila. Nature 1991. PubMed 2,474×
- Ridlon J.M., Kang D.J., Hylemon P.B. Bile salt biotransformations by human intestinal bacteria. J. Lipid Res 2006. PubMed 2,173×
- Abul-Husn N.S., Cheng X., Li A.H., Xin Y. et al. A protein-truncating HSD17B13 variant and protection from chronic liver disease. N. Engl. J. Med 2018. PubMed 676×
- Kotelevtsev Y., Holmes M.C., Burchell A., Houston P.M. et al. 11beta-hydroxysteroid dehydrogenase type 1 knockout mice show attenuated glucocorticoid-inducible responses and resist hyperglycemia on obesity or stress. Proc. Natl. Acad. Sci. U.S.A 1997. PubMed 751×
- Albiston A.L., Obeyesekere V.R., Smith R.E., Krozowski Z.S. Cloning and tissue distribution of the human 11 beta-hydroxysteroid dehydrogenase type 2 enzyme. Mol. Cell. Endocrinol 1994. PubMed 707×
- Wu L., Einstein M., Geissler W.M., Chan H.K. et al. Expression cloning and characterization of human 17 beta-hydroxysteroid dehydrogenase type 2, a microsomal enzyme possessing 20 alpha-hydroxysteroid dehydrogenase activity. J. Biol. Chem 1993. PubMed 376×
- Mune T., Rogerson F.M., Nikkilae H., Agarwal A.K. et al. Human hypertension caused by mutations in the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase. Nat. Genet 1995. PubMed 528×
- Tannin G.M., Agarwal A.K., Monder C., New M.I. et al. The human gene for 11 beta-hydroxysteroid dehydrogenase. Structure, tissue distribution, and chromosomal localization. J. Biol. Chem 1991. PubMed 409×
- Kreitman M., Hudson R.R. Inferring the evolutionary histories of the Adh and Adh-dup loci in Drosophila melanogaster from patterns of polymorphism and divergence. Genetics 1991. PubMed 265×
- Lustbader J.W., Cirilli M., Lin C., Xu H.W. et al. ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease. Science 2004. PubMed 1,104×
- Ma Y., Belyaeva O.V., Brown P.M., Fujita K. et al. 17-Beta hydroxysteroid dehydrogenase 13 is a hepatic retinol dehydrogenase associated with histological features of nonalcoholic fatty liver disease. Hepatology 2019. PubMed 254×
- Yan S.D., Fu J., Soto C., Chen X. et al. An intracellular protein that binds amyloid-beta peptide and mediates neurotoxicity in Alzheimer's disease. Nature 1997. PubMed 330×
- Wermuth B. Purification and properties of an NADPH-dependent carbonyl reductase from human brain. Relationship to prostaglandin 9-ketoreductase and xenobiotic ketone reductase. J. Biol. Chem 1981. PubMed 322×