PMID- 10434065
OWN - NLM
STAT- MEDLINE
DCOM- 19990927
LR  - 20190610
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1428
IP  - 2-3
DP  - 1999 Aug 5
TI  - Characterization of the CoA ligases of human liver mitochondria catalyzing the
      activation of short- and medium-chain fatty acids and xenobiotic carboxylic
      acids.
PG  - 455-62
AB  - Two distinct forms of xenobiotic/medium-chain fatty acid:CoA ligase (XM-ligase)
      were isolated from human liver mitochondria. They were referred to as HXM-A and
      HXM-B based on their order of elution from a DEAE-cellulose column. Activity of
      the two ligases was determined toward 15 different carboxylic acids. HXM-A
      represented 60-80% of the benzoate activity in the lysate, and kinetic analysis
      revealed that benzoate was the best substrate (highest V(max)/K(m)). The enzyme
      also had medium-chain fatty acid:CoA ligase activity. HXM-B had the majority of
      the hexanoate activity and hexanoate was its best substrate. It was, however,
      also active toward many xenobiotic carboxylic acids. Comparison of these two
      human XM-ligases with the previously characterized bovine XM-ligases indicated
      that they were kinetically distinct. When assayed with benzoic acid as substrate,
      both HXM-A and HXM-B had an absolute dependence on either Mg(2+) or Mn(2+) for
      activity. Further, addition of monovalent cation (K(+), Rb(+), or NH(4)(+))
      stimulated HXM-A activity by >30-fold and HXM-B activity by 4-fold. For both
      forms, activity toward straight-chain fatty acids was stimulated less by K(+)
      than was activity toward benzoate or phenylacetate. A 60 kDa short-chain fatty
      acid:CoA ligase was also isolated. It had activity toward propionate and
      butyrate, but not acetate, hexanoate or benzoate. The K(m)(app) values were high 
      but similar for propionate and butyrate (285 microM and 250 microM, respectively)
      but the V(max)(app) was nearly 6-fold greater with propionate as substrate. While
      the K(m) values are somewhat high, the enzyme is still more efficient with these 
      substrates than either of the XM-ligases.
FAU - Vessey, D A
AU  - Vessey DA
AD  - Liver Study Unit, Department of Veterans' Affairs Medical Center, San Francisco, 
      CA 94121, USA.
FAU - Kelley, M
AU  - Kelley M
FAU - Warren, R S
AU  - Warren RS
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Carboxylic Acids)
RN  - 0 (Fatty Acids)
RN  - 0 (Xenobiotics)
RN  - EC 6.2.1.- (Coenzyme A Ligases)
RN  - EC 6.2.1.- (xenobiotic medium chain fatty acid - coenzyme A ligase)
SB  - IM
MH  - Animals
MH  - Carboxylic Acids/metabolism
MH  - Cattle
MH  - Chromatography, Gel
MH  - Chromatography, Ion Exchange
MH  - Coenzyme A Ligases/chemistry/*metabolism
MH  - Fatty Acids/metabolism
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Kinetics
MH  - Mitochondria, Liver/*enzymology
MH  - Substrate Specificity
MH  - Xenobiotics/metabolism
EDAT- 1999/08/06 00:00
MHDA- 1999/08/06 00:01
CRDT- 1999/08/06 00:00
PHST- 1999/08/06 00:00 [pubmed]
PHST- 1999/08/06 00:01 [medline]
PHST- 1999/08/06 00:00 [entrez]
AID - S0304-4165(99)00088-4 [pii]
AID - 10.1016/s0304-4165(99)00088-4 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 1999 Aug 5;1428(2-3):455-62. doi:
      10.1016/s0304-4165(99)00088-4.