PMID- 10588950
OWN - NLM
STAT- MEDLINE
DCOM- 20000210
LR  - 20181130
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 40
IP  - 12
DP  - 1999 Dec
TI  - Phytanoyl-CoA hydroxylase from rat liver. Protein purification and cDNA cloning
      with implications for the subcellular localization of phytanic acid
      alpha-oxidation.
PG  - 2244-54
AB  - Phytanoyl-CoA hydroxylase (PhyH) catalyzes the conversion of phytanoyl-CoA to
      2-hydroxyphytanoyl-CoA, which is the first step in the phytanic acid
      alpha-oxidation pathway. Recently, several studies have shown that in humans,
      phytanic acid alpha-oxidation is localized in peroxisomes. In rat, however, the
      alpha-oxidation pathway has been reported to be mitochondrial. In order to
      clarify this differential subcellular distribution, we have studied the rat PhyH 
      protein. We have purified PhyH from rat liver to apparent homogeneity as judged
      by SDS-PAGE. Sequence analysis of two PhyH peptide fragments allowed cloning of
      the rat PHYH cDNA encoding a 38. 6 kDa protein. The deduced amino acid sequence
      revealed strong homology to human PhyH including the presence of a peroxisome
      targeting signal type 2 (PTS2). Heterologous expression of rat PHYH in
      Saccharomyces cerevisiae yielded a 38.6 kDa protein whereas the PhyH purified
      from rat liver had a molecular mass of 35 kDa. This indicates that PhyH is
      probably processed in rat by proteolytic removal of a leader sequence containing 
      the PTS2. This type of processing has been reported in several other peroxisomal 
      proteins that contain a PTS2. Subcellular localization studies using equilibrium 
      density centrifugation showed that PhyH is indeed a peroxisomal protein in rat.
      The finding that PhyH is peroxisomal in both rat and humans provides strong
      evidence against the concept of a differential subcellular localization of
      phytanic acid alpha-oxidation in rat and human.
FAU - Jansen, G A
AU  - Jansen GA
AD  - Department of Pediatrics (Emma Children's Hospital), University of Amsterdam,
      Academic Medical Centre, The Netherlands.
FAU - Ofman, R
AU  - Ofman R
FAU - Denis, S
AU  - Denis S
FAU - Ferdinandusse, S
AU  - Ferdinandusse S
FAU - Hogenhout, E M
AU  - Hogenhout EM
FAU - Jakobs, C
AU  - Jakobs C
FAU - Wanders, R J
AU  - Wanders RJ
LA  - eng
SI  - GENBANK/AF121345
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 0 (Carbon Radioisotopes)
RN  - 0 (DNA, Complementary)
RN  - 0 (Ketoglutaric Acids)
RN  - 14721-66-5 (Phytanic Acid)
RN  - EC 1.- (Mixed Function Oxygenases)
RN  - EC 1.14.- (PHYH protein, human)
RN  - EC 1.14.- (Phyh protein, rat)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Carbon Radioisotopes
MH  - Centrifugation, Density Gradient
MH  - Cloning, Molecular
MH  - DNA, Complementary/biosynthesis
MH  - Humans
MH  - Ketoglutaric Acids/metabolism
MH  - Liver/*enzymology
MH  - Male
MH  - Mixed Function Oxygenases/genetics/*isolation & purification/metabolism
MH  - Molecular Sequence Data
MH  - Oxidation-Reduction
MH  - Peroxisomes/enzymology
MH  - Phytanic Acid/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Saccharomyces cerevisiae/genetics
MH  - Sequence Homology, Amino Acid
MH  - Yeasts
EDAT- 1999/12/10 00:00
MHDA- 1999/12/10 00:01
CRDT- 1999/12/10 00:00
PHST- 1999/12/10 00:00 [pubmed]
PHST- 1999/12/10 00:01 [medline]
PHST- 1999/12/10 00:00 [entrez]
PST - ppublish
SO  - J Lipid Res. 1999 Dec;40(12):2244-54.