Effects of apolipoprotein C-II (apoC-II) on the lipolysis of very low density lipoproteins from apoC-II deficient patients

Matsuoka, N; Shirai, Kohji; Johnson, J D; Kashyap, Moti L.; Srivastava, Laxmi S.; Yamamura, Taku; Yamamoto, Akira; Saito, Y; Kumagai, Akira; Jackson, Richard L.

doi:10.1016/0026-0495(81)90029-9

Cited by 36 publications

(7 citation statements)

References 29 publications

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“…Our data have indicated that C-II has no effect on the apparent Km(TG) nor on Ks and that the only effect of the activator is to increase Fmax by increasing the catalytic rate constant, kp. The difference between our conclusions and those reached elsewhere (Schrecker & Greten, 1979; Matsuoka et al, 1981;Fitzharris et al, 1981) that C-II increases Km(TG) and has little effect on tzmax is undoubtedly due to differences in experimental design. In the cited papers, reaction velocities were determined at increasing TG concentrations and a constant ratio of C-ILTG concentrations.…”

Section: Discussioncontrasting

confidence: 99%

Kinetics of bovine milk lipoprotein lipase and the mechanism of enzyme activation by apolipoprotein C-II

Posner¹,

Wang²,

McConathy³

1983

Biochemistry

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The kinetics of bovine milk lipoprotein lipase (LPL) were studied in order to determine the reaction mechanism of this enzyme. Reaction velocities were determined at varying concentrations of emulsified trioleoylglycerol (TG) and different fixed concentrations of apolipoprotein C-II (C-II) or at varying C-II concentrations and different fixed concentrations of TG. Neither the apparent Km(TG) nor the apparent Km(C-II) was affected by varying the concentrations of C-II or TG, respectively. However, C-II increased the apparent Vmax for the enzyme about 20-fold. The following kinetic parameters were calculated from Lineweaver-Burk plots: Km(C-II) = 2.5 X 10(-8) M and Km (TG) = 2.5 X 10(-3) M. The dissociation constant (KS) of the enzyme-TG binary complex was determined from Scatchard plots to be 7.6 X 10(-8) M. Heparin was found to be a competitive dead-end inhibitor against both TG and C-II. Tricapryloylglycerol represented a competitive inhibitor against TG but a noncompetitive inhibitor against C-II. C-II was shown to interact with dansylated bovine milk LPL, increasing its fluorescent emission by inducing a conformational change in the enzyme. Based on these studies, it was concluded that the LPL-catalyzed reaction follows a random, bireactant, rapid-equilibrium mechanism and the role of C-II in the activation process involves an increase in the catalytic rate constant (Kp) resulting from conformational changes of LPL induced by C-II.

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Section: Discussioncontrasting

confidence: 99%

Kinetics of bovine milk lipoprotein lipase and the mechanism of enzyme activation by apolipoprotein C-II

Posner¹,

Wang²,

McConathy³

1983

Biochemistry

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“…21,22 Indeed, in hypertriglyceridemic patients, both the absolute concentrations of the different C apolipoproteins as well as the apo C-III to apo C-II ratio are increased, 8,20 both factors that may contribute to less efficient lipolysis by LPL as well as reduced apo E-dependent clearance. 14,17 Patients with hypertriglyceridemia are often treated with hypolipidemic drugs belonging to the class of fibrates.…”

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confidence: 99%

Developmental and Pharmacological Regulation of Apolipoprotein C-II Gene Expression

Andersson

Majd

Lefebvre

et al. 1999

ATVB

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Abstract-Increased plasma triglyceride concentrations are often observed in metabolic disorders predisposing to coronary heart disease. Among the major determinants of plasma triglyceride metabolism are the apolipoproteins (apos) of the C class, C-I, C-II, and C-III. Whereas physiological concentrations of apo C-II are required for lipolysis of triglycerides by lipoprotein lipase (LPL), overexpression of all 3 C apolipoproteins leads to hypertriglyceridemia. In the present study, we investigated apo C-II gene regulation under conditions associated with profound changes in plasma triglyceride metabolism, ie, during postnatal development and after treatment with the triglyceride-lowering fibrate drugs, and compared its expression to that of apo C-I and apo C-III. Whereas the expression of both apo C-I and apo C-III is low in fetal liver, increases gradually after birth, and attains maximal levels after weaning, apo C-II gene expression is already detectable in the fetal liver, increases rapidly immediately after birth, and remains elevated throughout suckling. Thus, the increased ingestion of lipids during suckling is met by an earlier induction of apo C-II, the obligatory activator for LPL, compared with apo C-III and apo C-I, which antagonize triglyceride catabolism. Treatment of rats with fibrates decreased apo C-II gene expression in the liver, but not in the intestine, whereas apo C-I gene expression did not change. The decrease of liver apo C-II mRNA levels after fenofibrate occurred in a time-and dose-dependent manner and was reversible but appeared less pronounced than the decrease of apo C-III mRNA. Apo C-II mRNA levels were not affected after treatment with BRL49653, a peroxisome proliferator-activated receptor (PPAR)␥-specific ligand, suggesting that fibrates act on apo C-II expression via PPAR␣. Addition of fenofibric acid to primary rat and human hepatocytes resulted in a decrease of apo C-II expression. In conclusion, fibrates decrease gene expression of apo C-II and apo C-III, but not apo C-I, in rat and human hepatocytes. This decrease of apo C-II and apo C-III gene expression, together with a lowered apo C-III to apo C-II ratio, should result in an improved clearance of triglyceride-rich remnant lipoproteins from plasma, without hampering triglyceride lipolysis by LPL.

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“…The whole homogenate was used for experiments. Lipoprotein lipase activity was determined using Triton X-100-emulsified [14C]trioleoyl glycerol emulsion according to the method of Matsuoka et al (1981). Incubations were carried out for indicated times at 3TC.…”

mentioning

confidence: 99%

“…VLDL was prepared by ultracentrifguation operated at 105,000 X g at d =1.006 for 18 hr. The extent of VLDL-[14C] triolein hydrolysis was determined according to the method previously reported (Matsuoka et al 1981).…”

mentioning

confidence: 99%

Existence of lipoprotein lipase in rat brain microvessels.

Shirai

Saitō

Yoshida

et al. 1986

Tohoku J. Exp. Med.

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Effects of apolipoprotein C-II (apoC-II) on the lipolysis of very low density lipoproteins from apoC-II deficient patients

Cited by 36 publications

References 29 publications

Kinetics of bovine milk lipoprotein lipase and the mechanism of enzyme activation by apolipoprotein C-II

Kinetics of bovine milk lipoprotein lipase and the mechanism of enzyme activation by apolipoprotein C-II

Developmental and Pharmacological Regulation of Apolipoprotein C-II Gene Expression

Existence of lipoprotein lipase in rat brain microvessels.

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