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ELSEVIER
FEES Letters 344 (t994) 239—241
FEBS 140¡9
LE TTERS
Inhibition of carnitine palmitoyltransferase 1 by hepatocyte swelling
Manuel Guzmána*. Guillermo Velascoa, José Castroa, Victor A. Zammitb
~Departmentof Biochernistrr ond Molecular Biology L Facuitv of Chernistry, Complutense University. 28040-Madrid, Spain
bHannah Research Institute, Ayr, KÁÓ SHL, Scotland. UK
Received 8 April 1994
Abstract
Incubation of hepatoc~tes under conditions known te increase their vo¡ume. i.e. with amino acids ev in bypo-osmotic medium.
decreased carnitine pa¡n,itoyi-transferase 1 (CPT-l) activity. Tbis effect of hepatocvte swe¡¡ing was antagonized by okadaic acid and dibutyry¡-cAMP.
Physio¡ogica¡ concentrations of g¡uramate inhibited CPT-l activity in digitonin-permeabi¡ized bepatocytes but not in iso¡ated n,itochondria. Resu¡ts
suggest that the amino acid-induced inhibition of CPT-¡ shares a common n,echanism with the amino acid-induced stimu¡ation of acety¡-CoA
carboxy¡ase and g¡ycogen synthase f(¡993) Eur. J. Biochen. 2¡7. ¡083—¡089].
Key words: Carnitjne palmitoyltransferase 1; l-lepatocyte swelling; Glutamine: Ketegenesis
1. Introduction 2. Experimental
Evidence is rapidly accumulating that changes in
hepatocyte volume play an important role in the control
of hepatocellular metabolic function [1,2]. Hepatocyte
swelling induced by several amino acids, notably glutaminc
amd proline. or by hypotonicity have a number of
anabolic and anti-catabolic effects. such as stimulation
of glycogen [3,4], lipid [4] and protein synthesis [5], or
¡nbibition of glycogenolysis [6] aud proteolysis [7]. Keto-
~enesis is also inhibited by hepatocyte swelling [8]. Although
the mechanism responsible for this effect has not
been described. amino acid-induced inhibition of hepatic
ketogenesis was observed te be independent of changes
tn the concentration of malonyl-CoA [8],a physiological
inhibitor of the key regulatory enzyme in the transport
of long-cbain fatty acids into the mitochondrial matrix,
viz. carnitine palmitoyltransferase 1 (CPT-l) [9—12].
Changes in the kinetic characteristics of CPT-I that
occur in parallel with, or independently of. intracellular
malonyl-CoA concentration have been shown te be involved
in a number of short- and long-ten alterations
of hepatic kctogenesis [9—12].Iherefore. the present
work was undertaken te test whether changes in the
intrinsic properties of CPT-I are involved in the amino
acid-induced inhibition of hepatic ketogencsis.
‘Corresponding author. Fax: (341 (¡) 394 4¡59.
O0¡4-5793/94/$7.O0© ¡994 Federation of EuropeanBiochemical Secieties.
lSD! 00 ¡ 4-5793