Membrane-associated N-myristoyltransferase activity is reduced in obese (fa/fa) Zucker rat liver.
N-Myristoyltransferase is the enzyme that catalyses the transfer of myristate from myristoyl-CoA to the NH2-terminal glycine residue of a number of protein of diverse functions. Many of the known myristoylated proteins are important in signal transduction. We have compared the activity of rat liver N-myristoyltransferase from lean and obese (fa/fa) Zucker rats (a model for non-insulin dependent diabetes mellitus, NIDDM). N-myristoyltransferase activity isolated from the particulate fraction of obese (fa/fa) Zucker rat liver was approximately 4.7-fold lower than the corresponding activity observed in either the controls or the vanadate-treated obese rat livers. This pattern was only observed in the particulate fraction; the homogenate and soluble N-myristoyltransferase activities were not significantly different to the control activities. N-myristoyltransferase activity isolated from the brain of the four groups showed no significant variations. These results, and previous work [King, M. J., Pugazhenthi, S., Khandelwal, R. L. and Sharma, R. K. (1993) Biochim. Biophys. Acta. 1165, 259-262], would indicate that the rat liver particulate N-myristoyltransferase activity appears to be inversely proportional to the level of plasma insulin, implicating insulin in the control of N-myristoylation. The specific activity of the particulate liver N-myristoyltransferase was approximately 10-fold higher than that of the soluble liver N-myristoyltransferase, raising the possibility that N-myristoyltransferase exists in 2 populations, with the active form of N-myristoyltransferase residing in the membranous fraction. This situation could provide a system whereby N-myristoylation is regulated by the translocation of N-myristoyltransferase from the cytosol to its active site in the membranes.
King
M J
MJ
Department of Pathology, Royal University Hospital, University of Saskatchewan, Canada.
Pugazhenthi
S
S
Khandelwal
R L
RL
Sharma
R K
RK
D000217:Acyltransferases / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology; D003920:Diabetes Mellitus / Q000201:enzymology*; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology; D007328:Insulin / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009765:Obesity / Q000201:enzymology* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology
D001786:Blood Glucose; D007328:Insulin; D014638:Vanadates; D000217:Acyltransferases; C050480:glycylpeptide N-tetradecanoyltransferase