D-erythrulose reductase (DER) is a 246-residue cytosolic short-chain dehydrogenase/reductase (SDR) of chicken that forms a homotetramer and is most abundant in kidney and liver. The enzyme purified from chicken liver reduces the tetrulose D-erythrulose to D-threitol using NADPH (preferred) or NADH, and also reduces vicinal diketones such as diacetyl, consistent with a role in reducing small alpha-dicarbonyl and sugar carbonyl compounds. DER belongs to the L-xylulose reductase/carbonyl reductase SDR family (PANTHER PTHR44252, subfamily SF3), which also contains the nematode DHS-21 and the mammalian dicarbonyl/L-xylulose reductases (DCXR, a sister subfamily); by descent it is predicted, but not shown in chicken, to reduce L-xylulose to xylitol.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004090 carbonyl reductase (NADPH) activity | IBA GO_REF:0000033 | ACCEPT | Summary: Family-level PAINT inference of NADPH-dependent carbonyl reduction from the PTHR44252 ancestral node PTN001211870, which lies above the SF1 (Cbr2), SF2 (mammalian DCXR) and SF3 (DER, DHS-21) split. Chicken DER is inside this clade, and the activity is independently supported in chicken: the purified liver enzyme reduces the alpha-diketone diacetyl (a ketone to secondary alcohol reduction) as well as D-erythrulose, with NADPH as the preferred cofactor. Reason: The node placement is phylogenetically sound and the activity is directly observed for the native chicken enzyme (diacetyl and D-erythrulose reduction; NADPH Km 7.9 uM). GO:0004090 (a secondary alcohol + NADP+ = a ketone + NADPH) is the right family-level description of the broad dicarbonyl reductase chemistry; the more specific D-erythrulose activity is captured by GO:0047880. Supporting Evidence: PMID:9538249 it can catalyze reduction of not only D-erythrulose but also such diketones as diacetyl PMID:7358641 NADH was less effective than NADPH and the Km's for NADH and NADPH were 67 micrometers and 7.9 micrometers, respectively |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell mapping to cytoplasm. DER was purified as a soluble enzyme from chicken liver extract, and its cloning paper notes that its subcellular localization differs from that of the closely related (mitochondrial) mouse tetrameric lung carbonyl reductase. Reason: A soluble cytosolic location is consistent with purification of the native enzyme from crude liver extract and with the stated contrast to the related tetrameric carbonyl reductase. No organelle targeting is reported. The evidence is indirect but nothing contradicts it, and cytoplasm is as precise as the available data allow. Supporting Evidence: PMID:12200544 these two enzymes have many biochemical differences; their substrate specificity, subcellular localization, organ distribution, etc. PMID:7358641 The overall purification of the enzyme was 164-fold from a crude extract. |
| GO:0005997 xylulose metabolic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT inference from node PTN001211870, grounded in experimental L-xylulose reduction by mammalian DCXR (SF2) and by C. elegans DHS-21, which shares PANTHER subfamily SF3 with chicken DER. L-xylulose metabolism has not been examined in chicken. Reason: The inference is phylogenetically reasonable: the function is present on both sides of the SF2/SF3 split (mammalian DCXR and DHS-21), so its loss in DER would need a lineage-specific event for which there is no evidence. However, chicken DER was characterized as highly specific for D-erythrulose, and no chicken study reports L-xylulose reduction or a role in xylulose metabolism, so this remains an inferred, non-core process for this protein. Supporting Evidence: PMID:21477590 Recombinant DHS-21 was shown to convert L-xylulose to xylitol using NADPH as a cofactor. PMID:11882650 catalyzed the oxidoreduction between xylitol and l-xylulose PMID:7358641 was highly specific to D-erythrulose with an apparent Km of 0.38 mM |
| GO:0006006 glucose metabolic process | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: PAINT inference whose donors are all mammalian DCXR (SF2); it reflects the proposed role of L-xylulose reductase in the uronate cycle of glucose metabolism. Unlike the xylulose terms, no SF3 member is among the donors. Reason: The link to glucose metabolism is indirect (via L-xylulose reduction in the uronate cycle) and is drawn from mammalian enzymes in a sister subfamily. Even for mammals the DCXR characterization paper states that the kidney localization suggests a role other than general carbohydrate metabolism. Chicken DER is a D-erythrulose (tetrose) reductase, and neither L-xylulose reduction nor uronate-cycle participation has been tested in chicken. The very broad term GO:0006006 overstates what is known for this protein. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN001211870 · PTN001211870 SUPPORTS SOURCE BUT NOT TARGET Node spans SF1/SF2/SF3; for this term all extant donors are mammalian DCXR (SF2), whose glucose-metabolism role is an indirect uronate-cycle inference. Chicken DER (SF3) is characterized as a D-erythrulose reductase with no uronate-cycle data. Supporting Evidence: PMID:11882650 the unique localization of the enzyme in kidney suggests that it has a role other than in general carbohydrate metabolism PMID:7358641 The enzyme was shown to catalyze the reduction of D-erythrulose to D-threitol |
| GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor | IEA GO_REF:0000117 | MODIFY | Summary: ARBA-derived general oxidoreductase term. Correct, but the chicken enzyme has directly demonstrated, more specific activities (D-erythrulose reductase and NADPH-dependent dicarbonyl/carbonyl reductase) that are is_a descendants of this term. Reason: The term is true but less specific than the evidence supports. Both GO:0047880 erythrulose reductase activity and GO:0004090 carbonyl reductase (NADPH) activity are descendants of GO:0016616 and are already carried by this gene, supported by the purified chicken enzyme. Proposed replacements: erythrulose reductase activity carbonyl reductase (NADPH) activity Supporting Evidence: PMID:7358641 The enzyme was shown to catalyze the reduction of D-erythrulose to D-threitol with the concomitant oxidation of NAD(P)H to NAD(P)+ PMID:9538249 it can catalyze reduction of not only D-erythrulose but also such diketones as diacetyl |
| GO:0047880 erythrulose reductase activity | IEA GO_REF:0000120 | ACCEPT | Summary: EC/Rhea-based IEA (EC 1.1.1.162). This is the defining, experimentally established activity of chicken DER: the enzyme purified and crystallized from chicken liver reduces D-erythrulose to D-threitol with NADPH (preferred) or NADH, with an apparent Km of 0.38 mM for D-erythrulose. Reason: Directly supported by enzymology of the native chicken enzyme, whose identity with Q8JIS3 is anchored by peptide sequencing of the purified protein in the cloning study. Although only an IEA row exists, the activity is experimentally established in this species and is the core function of the protein. Supporting Evidence: PMID:7358641 The enzyme was shown to catalyze the reduction of D-erythrulose to D-threitol with the concomitant oxidation of NAD(P)H to NAD(P)+, and was highly specific to D-erythrulose with an apparent Km of 0.38 mM PMID:12200544 Sequence analysis of a cDNA for D-erythrulose reductase from chicken liver showed that the deduced open reading frame encodes the protein with a molecular mass of 26 kDa consisting of 246 amino acids. |
| GO:0050038 L-xylulose reductase (NADPH) activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT inference from node PTN001211870. Donors include mammalian DCXR (SF2) and C. elegans DHS-21, which is in the same PANTHER subfamily (SF3) as chicken DER and has been shown to reduce L-xylulose with NADPH. L-xylulose reduction has not been reported for the chicken enzyme; UniProt describes it only as a probable activity. Reason: The activity is experimentally grounded on both sides of the SF2/SF3 split, so inheritance by DER is a reasonable phylogenetic inference, and the active-site residues are conserved with the family. But the native chicken enzyme was described as highly specific for D-erythrulose, and no chicken data on L-xylulose exist. The function is retained as an inferred, non-core activity; it should not be treated as experimentally established in chicken when used as a reference for transfer. Supporting Evidence: PMID:21477590 Recombinant DHS-21 was shown to convert L-xylulose to xylitol using NADPH as a cofactor. PMID:11882650 homotetramers with NADPH-linked reductase activity for alpha-dicarbonyl compounds, catalyzed the oxidoreduction between xylitol and l-xylulose |
| GO:0050038 L-xylulose reductase (NADPH) activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: EC/Rhea-based IEA (EC 1.1.1.10) derived from UniProt's "Probable L-xylulose reductase" alternative name, which is a similarity-based assignment rather than a measurement on the chicken enzyme. Reason: Consistent with the IBA row for the same term: a phylogenetically plausible but untested activity for chicken DER, kept as non-core. The chicken enzyme's demonstrated substrate preference is D-erythrulose. Supporting Evidence: PMID:21477590 Recombinant DHS-21 was shown to convert L-xylulose to xylitol using NADPH as a cofactor. PMID:7358641 was highly specific to D-erythrulose with an apparent Km of 0.38 mM |
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Download this section (compressed HTML)Q: Does chicken DER reduce L-xylulose to xylitol, and with what catalytic efficiency relative to D-erythrulose? The L-xylulose reductase annotation rests only on PANTHER subfamily SF3 membership shared with C. elegans DHS-21.
Q: What is the physiological source and fate of D-erythrulose/D-threitol in birds, i.e. which metabolic process does DER serve beyond the reaction itself?
Experiment: Express recombinant chicken DER and measure kinetics with D-erythrulose, L-xylulose, diacetyl and other alpha-dicarbonyls side by side with human DCXR and C. elegans DHS-21, to establish whether substrate preference diverges between PANTHER subfamilies SF2 and SF3.
Type: enzyme kinetics
Experiment: Determine the stereochemistry of the acetoin produced from diacetyl by chicken DER, which would allow assignment of a specific diacetyl reductase activity term.
Type: enzyme assay
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