PMID- 10601301
OWN - NLM
STAT- MEDLINE
DCOM- 20000113
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 52
DP  - 1999 Dec 24
TI  - Cloning, expression, and fatty acid regulation of the human delta-5 desaturase.
PG  - 37335-9
AB  - Arachidonic (20:4(n-6)), eicosapentaenoic (20:5(n-3)), and docosahexaenoic
      (22:6(n-3)) acids are major components of brain and retina phospholipids,
      substrates for eicosanoid production, and regulators of nuclear transcription
      factors. One of the two rate-limiting steps in the production of these polyenoic 
      fatty acids is the desaturation of 20:3(n-6) and 20:4(n-3) by Delta-5 desaturase.
      This report describes the cloning and expression of the human Delta-5 desaturase,
      and it compares the structural characteristics and nutritional regulation of the 
      Delta-5 and Delta-6 desaturases. The open reading frame of the human Delta-5
      desaturase encodes a 444-amino acid peptide which is identical in size to the
      Delta-6 desaturase and which shares 61% identity with the human Delta-6
      desaturase. The Delta-5 desaturase contains two membrane-spanning domains, three 
      histidine-rich regions, and a cytochrome b(5) domain that all align perfectly
      with the same domains located in the Delta-6 desaturase. Expression of the open
      reading frame in Chinese hamster ovary cells instilled the ability to convert
      20:3(n-6) to 20:4(n-6). Northern analysis revealed that many human tissues
      including skeletal muscle, lung, placenta, kidney, and pancreas expressed Delta-5
      desaturase mRNA, but Delta-5 desaturase was most abundant in the liver, brain,
      and heart. However, in all tissues, the abundance of Delta-5 desaturase mRNA was 
      much lower than that observed for the Delta-6 desaturase. When rats were fed a
      diet containing 10% safflower oil or menhaden fish oil, the level of hepatic mRNA
      for Delta-5 and Delta-6 desaturase was only 25% of that found in the liver of
      rats fed a fat-free diet or a diet containing triolein. Finally, a BLAST and
      Genemap search of the human genome revealed that the Delta-5 and Delta-6
      desaturase genes reside in reverse orientation on chromosome 11 and that they are
      separated by <11,000 base pairs.
FAU - Cho, H P
AU  - Cho HP
AD  - Program of Nutritional Sciences and the Institute for Cellular and Molecular
      Biology, The University of Texas-Austin, Austin, Texas 78712, USA.
FAU - Nakamura, M
AU  - Nakamura M
FAU - Clarke, S D
AU  - Clarke SD
LA  - eng
GR  - DK 53872/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
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 (Fatty Acids)
RN  - 0 (RNA, Messenger)
RN  - EC 1.14.19.- (Fatty Acid Desaturases)
RN  - EC 1.14.19.3 (Linoleoyl-CoA Desaturase)
RN  - EC 1.14.99.- (delta-5 fatty acid desaturase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - CHO Cells
MH  - Cloning, Molecular
MH  - Cricetinae
MH  - Fatty Acid Desaturases/chemistry/*genetics
MH  - Fatty Acids/*pharmacology
MH  - Gene Expression Regulation, Enzymologic/*drug effects
MH  - Humans
MH  - Linoleoyl-CoA Desaturase
MH  - Molecular Sequence Data
MH  - Open Reading Frames
MH  - RNA, Messenger/analysis
EDAT- 1999/12/22 00:00
MHDA- 1999/12/22 00:01
CRDT- 1999/12/22 00:00
PHST- 1999/12/22 00:00 [pubmed]
PHST- 1999/12/22 00:01 [medline]
PHST- 1999/12/22 00:00 [entrez]
AID - 10.1074/jbc.274.52.37335 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Dec 24;274(52):37335-9. doi: 10.1074/jbc.274.52.37335.