Stimulation of rat liver mitochondrial sn-glycerol-3-phosphate acyltransferase by polymyxin B via enhanced extraction of lysophosphatidic acid.
The purpose of this investigation was to determine how polymyxin B stimulates the activity of mitochondrial glycerophosphate acyltransferase. Polymyxin B did not change the integrity of the mitochondrial outer membrane as judged by testing the latency (>80%) of cytochrome oxidase activity. The stimulation totally disappeared when polymyxin B-treated mitochondria were washed. The FA side chain in polymyxin B was unnecessary for stimulation, as the nonapeptide was as effective as the whole antibiotic. The stimulation by polymyxin B or the nonapeptide was observed only in the presence of BSA. Cytochrome c, when added to the incubation medium instead of albumin, did not stimulate the mitochondrial enzyme, but did produce a stimulatory effect of polymyxin B on the mitochondrial acyltransferase. As reported earlier for the bacterial and microsomal acyltransferase, other polycationic compounds such as spermine and spermidine stimulated mitochondrial glycerophosphate acyltransferase. The stimulation of the mitochondrial acyltransferase by spermine and spermidine also occurred only in the presence of BSA. The analysis of the products of esterification demonstrated the presence of more lysophosphatidic acid (LPA) in the polymyxin B- and polyamine-stimulated assays in comparison to their respective control. Furthermore, in comparison to the albumin-treated control, there was 60% more LPA present in the assay supernatant fractions of polymyxin B-treated samples. Our results suggest that polymyxin B stimulates the mitochondrial glycerophosphate acyltransferase activity by enhancing the extraction of more LPA from the mitochondria to the supernatant fraction.
Roy
Arun
A
St. John's University, Department of Biological Sciences, Jamaica, New York 11439, USA.
Guha
Nilanjan
N
Veras
Ingrid D
ID
Chakraborty
Sanjoy
S
Haldar
Dipak
D
D000215:Acylation / Q000187:drug effects; D000818:Animals; D002417:Cattle; D045304:Cytochromes c / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism*; D007425:Intracellular Membranes / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008246:Lysophospholipids / Q000302:isolation & purification / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D011073:Polyamines / Q000494:pharmacology; D011112:Polymyxin B / Q000494:pharmacology*; D011489:Protein Denaturation / Q000187:drug effects; D051381:Rats; D012709:Serum Albumin / Q000494:pharmacology
D005227:Fatty Acids; D008246:Lysophospholipids; D011073:Polyamines; D012709:Serum Albumin; D045304:Cytochromes c; D003576:Electron Transport Complex IV; D005992:Glycerol-3-Phosphate O-Acyltransferase; D011112:Polymyxin B