LPD1/YFL018C Summary Help

Standard Name LPD1 1
Systematic Name YFL018C
Alias HPD1
Feature Type ORF, Verified
Description Dihydrolipoamide dehydrogenase; the lipoamide dehydrogenase component (E3) of the pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase multi-enzyme complexes; LPD1 has a paralog, IRC15, that arose from the whole genome duplication (2, 3 and see Summary Paragraph)
Name Description LiPoamide Dehydrogenase 1
Chromosomal Location
ChrVI:103127 to 101628 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All LPD1 GO evidence and references
  View Computational GO annotations for LPD1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 11 genes
Classical genetics
Large-scale survey
65 total interaction(s) for 49 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 32
  • Affinity Capture-RNA: 2
  • Two-hybrid: 1

Genetic Interactions
  • Dosage Growth Defect: 1
  • Negative Genetic: 11
  • Phenotypic Enhancement: 1
  • Phenotypic Suppression: 1
  • Positive Genetic: 8
  • Synthetic Growth Defect: 5
  • Synthetic Lethality: 2
  • Synthetic Rescue: 1

Expression Summary
Length (a.a.) 499
Molecular Weight (Da) 54,010
Isoelectric Point (pI) 8.11
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrVI:103127 to 101628 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1500 103127..101628 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000001876

LPD1 encodes dihydrolipoamide dehydrogenase, which is found in the mitochondrial matrix (4, 2) and is an essential enzyme required for the glycine cleavage system, glycolysis and TCA cycle. Lpd1p is a component of the glycine decarboxylase complex (GDC), 2-oxoglutarate dehydrogenase (OGDH), and pyruvate dehydrogenase (PDH) complexes (4, 5). Mutations in LPD1 abolish activity of the glycine decarboxylase, 2-oxoglutarate dehydrogenase, and pyruvate dehydrogenase complexes (6, 7, 8). GDC is a multienzyme complex that catalyzes the reversible oxidative cleavage of glycine into CO2 and NH3 and connects the metabolism of one, two and three-carbon compounds as shown in this pathway diagram (9). PDH catalyses the conversion of pyruvate to acetyl-CoA while OGDH catalyses the oxidative decarboxylation of 2-oxoglutarate to succinyl-CoA, which is part of the TCA cycle (4). In order to bind to the E2 (Lat1p) core of the pyruvate dehydrogenase complex, Lpd1p (E3) requires the activity of Pdx1p (Lpd1p-binding protein; Protein X) (10).

LPD1 is subject to catabolite repression and transcription of LPD1 for release from glucose repression is activated by the HAP2/HAP3/HAP4 transcription factor complex (11). In addition, LPD1 is also regulated by the Gcn4p transcription factor under conditions of amino acid starvation (8).

Lpd1p has strong sequence similarity to dihydrolipoamide dehydrogenases in prokaryotes and mammals (2, 12). Mutations in DLD, the human dihydrolipoamide dehydrogenase gene, are responsible for some cases of lactic acidosis (maple syrup urine disease, type III) (OMIM) (13).

Last updated: 2008-04-03 Contact SGD

References cited on this page View Complete Literature Guide for LPD1
1) Dickinson JR, et al.  (1986) A mutation affecting lipoamide dehydrogenase, pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase activities in Saccharomyces cerevisiae. Mol Gen Genet 204(1):103-7
2) Ross J, et al.  (1988) The nucleotide sequence of the LPD1 gene encoding lipoamide dehydrogenase in Saccharomyces cerevisiae: comparison between eukaryotic and prokaryotic sequences for related enzymes and identification of potential upstream control sites. J Gen Microbiol 134(5):1131-9
3) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
4) Pronk JT, et al.  (1996) Pyruvate metabolism in Saccharomyces cerevisiae. Yeast 12(16):1607-33
5) Roy DJ and Dawes IW  (1987) Cloning and characterization of the gene encoding lipoamide dehydrogenase in Saccharomyces cerevisiae. J Gen Microbiol 133(4):925-33
6) Sinclair DA and Dawes IW  (1995) Genetics of the synthesis of serine from glycine and the utilization of glycine as sole nitrogen source by Saccharomyces cerevisiae. Genetics 140(4):1213-22
7) Dickinson JR, et al.  (1997) A 13C nuclear magnetic resonance investigation of the metabolism of leucine to isoamyl alcohol in Saccharomyces cerevisiae. J Biol Chem 272(43):26871-8
8) Zaman Z, et al.  (1999) Transcription factor GCN4 for control of amino acid biosynthesis also regulates the expression of the gene for lipoamide dehydrogenase. Biochem J 340 ( Pt 3)():855-62
9) Gelling CL, et al.  (2004) Identification of a novel one-carbon metabolism regulon in Saccharomyces cerevisiae. J Biol Chem 279(8):7072-81
10) Lawson JE, et al.  (1991) Disruption and mutagenesis of the Saccharomyces cerevisiae PDX1 gene encoding the protein X component of the pyruvate dehydrogenase complex. Biochemistry 30(11):2834-9
11) Bowman SB, et al.  (1992) Positive regulation of the LPD1 gene of Saccharomyces cerevisiae by the HAP2/HAP3/HAP4 activation system. Mol Gen Genet 231(2):296-303
12) Browning KS, et al.  (1988) Nucleotide sequence for yeast dihydrolipoamide dehydrogenase. Proc Natl Acad Sci U S A 85(6):1831-4
13) Foury F  (1997) Human genetic diseases: a cross-talk between man and yeast. Gene 195(1):1-10