No abstract

The dose response to alcohol use of carbohydrate-deficient transferrin (CDT), γ-glutamyltransferase (GGT), and their combination (γ-CDT) was studied in an age-and gender-stratified, random sample from Finland in 1997. A linear association with a threshold between alcohol consumption and the three markers was observed. Body mass index was negatively associated with CDT and positively with GGT. Age was positively associated with GGT and γ-CDT. In conclusion, CDT appears to be an early phase marker of alcohol consumption. The combined marker, γ-CDT, was less associated with factors such as body mass index but more strongly correlated with alcohol consumption than were the two markers separately. Am J Epidemiol 2000;152:747-51.

Microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase kinase activity is enhanced about 5 fold by 2mM of either AMP or ADP. Activation constants, K a , for AMP and ADP are 17μΜ and 430μΜ respectively, showing that AMP is a more potent activator than ADP. This property is expressed by increasing not only the rate of reductase inactivation but also the rate of reductase phosphorylation from [γ-32 Ρ]ΑΤΡ. GTP can replace ATP as substrate of reductase kinase but GMP and GDP cannot replace AMP as activators. Kinetic studies show that ATP can only act as a substrate. Nucleoside mono or diphosphates and nucleoside triphosphates, thus, appear to bind to different sites on microsomal HMG-CoA reductase kinase. Nucleoside mono or diphosphates act as allosteric activators of reductase kinase. The adenosyl moiety and the unaltered phosphate ester at the 5' position are two essential features of the activator molecule. Phosphorylation of reductase either by microsomal or cytosolic AMP-activated reductase kinase produces an 80% inactivation, with a concomitant incorporation of 0.8 mol of 32 P per mol of reductase (M T 55 000). In both cases exhaustive tryptic digestion of 32 P-labeled HMG-CoA reductase, which had been denatured in 2M urea, yields two major phosphopeptides, the phosphoryl group being bound to serine residues. Allosterische Aktivierung der [Hydroxymethylglutaryl-CoA-Reduktase-(NADPH)]-Kinase aus Rattenlebermikrosomen durch NucleosidphosphateZusammenfassung: Die Aktivit t der mikrosomalen3-Hydroxy-3-methylglutaryl-Coenzym-A-(HMG-CoA-)Reduktase-Kinase wird durch 2mM AMP oder ADP etwa 5 fach erh ht. Die Aktivierungskonstanten, KZ , f r AMP und ADP sind 17 bzw. 430μΜ, d.h. AMP ist als Aktivator effektiver als ADP. Aufgrund dieser Eigenschaft wird nicht nur die Geschwindigkeit der Reduktase-Inaktivierung erh ht, sondern auch die der Reduktase-Phosphorylierung mittels [γ-32 Ρ]ΑΤΡ. GTP kann das ATP als Substrat der ReduktaseKinase ersetzen, aber GMP and GDP k nnen nicht AMP als Aktivator ersetzen. Kinetische Untersuchungen zeigen, da ATP nur als Substrat reagieren kann. Offenbar haben also die Nucleosidmono-und -diphosphate einerseits und die Nucleosidtriphosphate andererseits unterschiedliche Bindungsstellen auf der HMG-

Compared with single markers, a significant improvement of sensitivity was obtained when the combination of both markers was used, especially in females.

Compared with single markers, a significant improvement of sensitivity was obtained when the combination of both markers was used, especially in females.