PMID- 10521434
OWN - NLM
STAT- MEDLINE
DCOM- 19991123
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 43
DP  - 1999 Oct 22
TI  - The human PICD gene encodes a cytoplasmic and peroxisomal NADP(+)-dependent
      isocitrate dehydrogenase.
PG  - 30527-33
AB  - Human PICD was identified by homology probing the data base of expressed sequence
      tags with the protein sequence of Saccharomyces cerevisiae Idp3p, a peroxisomal
      NADP(+)-dependent isocitrate dehydrogenase. The human PICD cDNA contains a
      1242-base pair open reading frame, and its deduced protein sequence is 59%
      identical to yeast Idp3p. Expression of PICD partially rescued the fatty acid
      growth defect of the yeast idp3 deletion mutant suggesting that PICD is
      functionally homologous to Idp3p. Kinetic studies on bacterially expressed PICD
      demonstrated that this enzyme catalyzed the oxidative decarboxylation of
      isocitrate to 2-oxoglutarate with a specific activity of 22.5 units/mg and that
      PICD displayed K(M) values of 76 microM for isocitrate and 112 microM for
      NADP(+). In subcellular fractionation experiments, we found PICD in both
      peroxisomes and cytoplasm of human and rat liver cells, with approximately 27% of
      total PICD protein associated with peroxisomes. The presence of PICD in mammalian
      peroxisomes suggests roles in the regeneration of NADPH for intraperoxisomal
      reductions, such as the conversion of 2, 4-dienoyl-CoAs to 3-enoyl-CoAs, as well 
      as in peroxisomal reactions that consume 2-oxoglutarate, namely the
      alpha-hydroxylation of phytanic acid. As for cytoplasmic PICD, the phenotypes of 
      patients with glucose-6-phosphate dehydrogenase deficiency (Luzzatto, L., and
      Mehta, A. (1995) in The Metabolic and Molecular Bases of Inherited Disease
      (Scriver, C. R., Beaudet, A. L., Sly, W. S., and Valle, D., eds) Vol. 3, 7th Ed.,
      pp. 3367-3398, McGraw-Hill Inc., New York) suggest that PICD serves a significant
      role in cytoplasmic NADPH production, particularly under conditions that do not
      favor the use of the hexose monophosphate shunt (Luzzatto et al.).
FAU - Geisbrecht, B V
AU  - Geisbrecht BV
AD  - Department of Biological Chemistry, The Johns Hopkins University School of
      Medicine, Baltimore, Maryland 21205, USA.
FAU - Gould, S J
AU  - Gould SJ
LA  - eng
SI  - GENBANK/AF113917
GR  - DK45787/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Recombinant Proteins)
RN  - EC 1.1.1.41 (Isocitrate Dehydrogenase)
RN  - EC 1.1.1.42 (isocitrate dehydrogenase (NADP+))
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Pairing
MH  - Base Sequence
MH  - Cell Fractionation
MH  - Cloning, Molecular
MH  - Cytoplasm/enzymology
MH  - Humans
MH  - Isocitrate Dehydrogenase/chemistry/*genetics/*metabolism
MH  - Kinetics
MH  - Liver/*enzymology
MH  - Molecular Sequence Data
MH  - Open Reading Frames
MH  - Peroxisomes/*enzymology
MH  - Rats
MH  - Recombinant Proteins/chemistry/metabolism
MH  - Saccharomyces cerevisiae/enzymology/growth & development
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Tumor Cells, Cultured
EDAT- 1999/10/16 00:00
MHDA- 1999/10/16 00:01
CRDT- 1999/10/16 00:00
PHST- 1999/10/16 00:00 [pubmed]
PHST- 1999/10/16 00:01 [medline]
PHST- 1999/10/16 00:00 [entrez]
AID - 10.1074/jbc.274.43.30527 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Oct 22;274(43):30527-33. doi: 10.1074/jbc.274.43.30527.