PMID- 10064899
OWN - NLM
STAT- MEDLINE
DCOM- 19990413
LR  - 20190610
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1437
IP  - 2
DP  - 1999 Feb 25
TI  - A specific human lysophospholipase: cDNA cloning, tissue distribution and kinetic
      characterization.
PG  - 157-69
AB  - Lysophospholipases are critical enzymes that act on biological membranes to
      regulate the multifunctional lysophospholipids; increased levels of
      lysophospholipids are associated with a host of diseases. Herein we report the
      cDNA cloning of a human brain 25 kDa lysophospholipid-specific lysophospholipase 
      (hLysoPLA). The enzyme (at both mRNA and protein levels) is widely distributed in
      tissues, but with quite different abundances. The hLysoPLA hydrolyzes
      lysophosphatidylcholine in both monomeric and micellar forms, and exhibits
      apparent cooperativity and surface dilution kinetics, but not interfacial
      activation. Detailed kinetic analysis indicates that the hLysoPLA binds first to 
      the micellar surface and then to the substrate presented on the surface. The
      kinetic parameters associated with this surface dilution kinetic model are
      reported, and it is concluded that hLysoPLA has a single substrate binding site
      and a surface recognition site. The apparent cooperativity observed is likely due
      to the change of substrate presentation. In contrast to many non-specific
      lipolytic enzymes that exhibit lysophospholipase activity, hLysoPLA hydrolyzes
      only lysophospholipids and has no other significant enzymatic activity. Of
      special interest, hLysoPLA does not act on plasmenylcholine. Of the several
      inhibitors tested, only methyl arachidonyl fluorophosphonate (MAFP) potently and 
      irreversibly inhibits the enzymatic activity. The inhibition by MAFP is
      consistent with the catalytic mechanism proposed for the enzyme - a serine
      hydrolase with a catalytic triad composed of Ser-119, Asp-174 and His-208.
FAU - Wang, A
AU  - Wang A
AD  - Department of Chemistry and Biochemistry, University of California at San Diego, 
      La Jolla, CA 92093-0601, USA.
FAU - Yang, H C
AU  - Yang HC
FAU - Friedman, P
AU  - Friedman P
FAU - Johnson, C A
AU  - Johnson CA
FAU - Dennis, E A
AU  - Dennis EA
LA  - eng
GR  - GM 2050/GM/NIGMS NIH HHS/United States
GR  - GM 51606/GM/NIGMS NIH HHS/United States
GR  - HD 26171/HD/NICHD 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  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (DNA, Complementary)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.5 (Lysophospholipase)
RN  - EC 3.1.4.- (Phosphoric Diester Hydrolases)
RN  - EC 3.1.4.1 (ectonucleotide pyrophosphatase phosphodiesterase 1)
RN  - EC 3.6.1.- (Pyrophosphatases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Brain/enzymology
MH  - Cloning, Molecular
MH  - DNA, Complementary/biosynthesis
MH  - Escherichia coli/genetics/metabolism
MH  - Gene Expression
MH  - Humans
MH  - Kinetics
MH  - Lysophospholipase/biosynthesis/chemistry/*genetics
MH  - Membrane Glycoproteins/pharmacology
MH  - Molecular Sequence Data
MH  - Muscle, Skeletal/enzymology
MH  - Myocardium/enzymology
MH  - Phospholipases A/analysis
MH  - *Phosphoric Diester Hydrolases
MH  - Placenta/enzymology
MH  - *Pyrophosphatases
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Recombinant Proteins/chemistry
MH  - Substrate Specificity
EDAT- 1999/03/05 00:00
MHDA- 1999/03/05 00:01
CRDT- 1999/03/05 00:00
PHST- 1999/03/05 00:00 [pubmed]
PHST- 1999/03/05 00:01 [medline]
PHST- 1999/03/05 00:00 [entrez]
AID - S1388-1981(99)00012-8 [pii]
AID - 10.1016/s1388-1981(99)00012-8 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 1999 Feb 25;1437(2):157-69. doi:
      10.1016/s1388-1981(99)00012-8.