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MetaCyc Enzyme: 3-ketodihydrosphinganine reductase

Gene: TSC10A Accession Number: AT3G06060 (MetaCyc)

Synonyms: 3-oxosphinganine reductase, 3-oxosphinganine:NADPH oxidoreductase

Species: Arabidopsis thaliana col

Summary:
TSC10A is a 3-ketodihydrosphinganine (KDS) reductase based on genetic complementation of a yeast mutant and direct enzymatic assays using recombinant TSC10A expressed in yeast. A functional GFP-tagged TSC10A fusion protein localizes in the ER membrane, and, like its yeast ortholog, this Arabidopsis protein appears to have its C-terminus on the cytoplasmic face of the ER, however, unlike Tsc10p from yeast, this Arabidopsis protein appears to have its N-terminus on the lumenal face of the ER [Chao11]. There are also some interesting differences in the specificities of the enzymes from the two species. While the yeast Tsc10p enzyme only acts with NADPH, the TSC10A and TSC10B orthologs can also use NADH, albeit with less activity. All three enzymes, including TSC10A seem to be relatively promiscuous and can catalyze the reduction of sphinganines with chain lengths varying from 12 to 20 carbons. But, of the two related genes in Arabidopsis, TSC10A has a unique ability to produce not only the biologically relevant D-erythro form of dihydrosphingosine (DHS), but also the L-threo form that appears to have anti-cancer properties [Morales07, Chao11].

Mutant plants with a disrupted TSC10A gene have altered ionomes, with increased levels of Na, K, and Rb and decreased levels of Ca, Mg, Fe, and Mo in their leaves. tsc10a-2 mutants also have higher levels of ceramides and hydroxyceramides than wild type plants but their levels of glucosylceramides are reduced. These mutants also have an altered suberin composition and deposition pattern in their roots, possibly as a result of lipid raft perturbations caused by the alterations in sphingolipid metabolism [Chao11, Lahner03].

TSC10A appears to be responsible for the majority of the KDS reductase activity in Arabidopsis since tsc10a-2 mutants have lost most of this activity, despite the presence of a wild type copy of the TSC10B gene. However, TSC10B likely also contributes to total KDS reductase activity in vivo based on the observation that tsc10a tsc10b double mutants are not viable [Chao11].

Locations: endoplasmic reticulum membrane

Map Position: [1,827,986 -> 1,830,206]

Unification Links: ArrayExpress:Q9M7S9 , PhylomeDB:Q9M7S9 , Phytozome Plant Orthologs:AT3G06060.1 , Pride:Q9M7S9 , Protein Model Portal:Q9M7S9 , SMR:Q9M7S9 , TAIR:AT3G06060 , UniProt:Q9M7S9

Relationship Links: InterPro:IN-FAMILY:IPR002198 , InterPro:IN-FAMILY:IPR002347 , InterPro:IN-FAMILY:IPR016040 , InterPro:IN-FAMILY:IPR020904 , Pfam:IN-FAMILY:PF00106 , Prints:IN-FAMILY:PR00081 , Prosite:IN-FAMILY:PS00061

Gene-Reaction Schematic: ?

GO Terms:

Cellular Component: GO:0005789 - endoplasmic reticulum membrane [Chao11]

Gene Class: UNCLASSIFIED

Credits:
Created 15-Sep-2011 by Dreher KA , PMN


Enzymatic reaction of: 3-ketodihydrosphinganine reductase

Synonyms: 3-ketodihydrosphinganine (C18) reductase

EC Number: 1.1.1.102

sphinganine + NADP+ <=> 3-dehydrosphinganine + NADPH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the opposite direction.

In Pathways: sphingolipid biosynthesis (plants)

Summary:
Based on assays performed using HA-tagged TSC10A present in yeast microsomes, the specific activity of this enzyme appears to be ~85 μmol mg-1 min-1 [Chao11].


Enzymatic reaction of: 3-ketodihydrosphinganine (C18) reductase (3-ketodihydrosphinganine reductase)

EC Number: 1.1.1.102

L-threo-sphinganine + NADP+ <=> 3-dehydrosphinganine + NADPH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

Reversibility of this reaction is unspecified.


Enzymatic reaction of: 3-ketodihydrosphinganine reductase

EC Number: 1.1.1.102

sphinganine + NADP+ <=> 3-dehydrosphinganine + NADPH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the opposite direction.

In Pathways: sphingolipid biosynthesis (plants)


Enzymatic reaction of: 3-ketodihydrosphinganine (C20) reductase (3-ketodihydrosphinganine reductase)

EC Number: 1.1.1.102

sphinganine (C20) + NADP+ <=> 3-dehydrosphinganine (C20) + NADPH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

Reversibility of this reaction is unspecified.


Enzymatic reaction of: 3-ketodihydrosphinganine (C18) reductase (3-ketodihydrosphinganine reductase)

Synonyms: 3-ketodihydrosphinganine reductase

EC Number: 1.1.1.-

a sphinganine + NAD+ <=> 3-dehydrosphinganine + NADH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

Reversibility of this reaction is unspecified.


References

Chao11: Chao DY, Gable K, Chen M, Baxter I, Dietrich CR, Cahoon EB, Guerinot ML, Lahner B, Lu S, Markham JE, Morrissey J, Han G, Gupta SD, Harmon JM, Jaworski JG, Dunn TM, Salt DE (2011). "Sphingolipids in the root play an important role in regulating the leaf ionome in Arabidopsis thaliana." Plant Cell 23(3);1061-81. PMID: 21421810

Lahner03: Lahner B, Gong J, Mahmoudian M, Smith EL, Abid KB, Rogers EE, Guerinot ML, Harper JF, Ward JM, McIntyre L, Schroeder JI, Salt DE (2003). "Genomic scale profiling of nutrient and trace elements in Arabidopsis thaliana." Nat Biotechnol 21(10);1215-21. PMID: 12949535

Morales07: Morales PR, Dillehay DL, Moody SJ, Pallas DC, Pruett S, Allgood JC, Symolon H, Merrill AH (2007). "Safingol toxicology after oral administration to TRAMP mice: demonstration of safingol uptake and metabolism by N-acylation and N-methylation." Drug Chem Toxicol 30(3);197-216. PMID: 17613006


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Mon Dec 22, 2014, biocyc13.