Localization of a conformational energy-coupling determinant near the C terminus of the beta subunit of the F1F0-ATPase.

Escherichia coli mutants in the beta subunit of the F1F0-ATPase can be complemented with the beta subunit from the obligate aerobe Bacillus megaterium. It has been shown that cells carrying such hybrid ATPases have an unusual energy-coupling phenotype. Although they are able to grow on minimal succinate medium, and therefore carry a functional ATP synthase, they are defective in the ability to grow anaerobically, indicating some defect in ATP-driven proton pumping (Scarpetta, M., Hawthorne, C. A., and Brusilow, W. S. A. (1991) J. Biol. Chem. 266, 18567-18572). In this study, chimeric beta subunits were constructed consisting of the E. coli or the B. megaterium beta subunit carrying the C-terminal 18% of the other's beta subunit. The phenotypes of an E. coli beta mutant complemented with these chimeric subunits showed that the energy-coupling defect was located in this C-terminal region. The E. coli beta subunit carrying the B. megaterium C-terminal region displayed the energy-coupling defect, while the B. megaterium beta subunit carrying the E. coli C-terminal region did not. In ATP-dependent fluorescence quenching assays, membranes isolated from cells displaying the energy-coupling defect also pumped protons less well than membranes isolated from cells that were able to grow anaerobically. These results demonstrate that the C terminus of the beta subunit is involved in the conformational coupling pathway, which, through the polypeptide backbone of the beta subunit, physically links ATP synthesis or hydrolysis to the energy of proton translocation.

Effects of BM 13.177, a new antiplatelet drug in patients with atherosclerotic disease.

Seven males with atherosclerotic disease received daily 1.6 g of the thromboxane antagonist BM 13.177 in two separate oral dosages over a period of four days. The drug significantly reduced elevated plasma levels of thromboxane B2, beta-thromboglobulin and platelet factor 4, whereas thromboxane B2 generation was only slightly depressed. BM 13.177 inhibited platelet aggregation by collagen, and to a minor degree the second wave of ADP induced aggregation. Platelet sensitivity to prostacyclin and aggregation by ristocetin were not altered. Bleeding time was prolonged. All effects disappeared within 24 hours after the last application of the drug. No side effects were noted. Thus BM 13.177 appears to be a safe and effective new antiplatelet drug.

Guar and its effects on metabolic control in type II diabetic subjects.

The effect of guar mini-tablets (5 g t.i.d.) on carbohydrate and lipid metabolism of outpatients with overt diabetes mellitus with glycosuria (is greater than 5 g/24 h) was determined in an open-controlled, randomized, multicenter, crossover study. A 4-wk pretreatment period was followed by a 6-wk treatment period. The treatment period consisted of a 2-wk guar period (treatment period II), which was followed by the wash-out period. The other half of the patients received treatment in the reverse order. Out of 93 patient records, 79 (41 sulfonylurea [SU] and 38 insulin-treated) were suitable for statistical analysis. No relevant weight-reducing effect of guar could be found in both 2-wk treatment periods. At the end of treatment period II, the lowering of the 1-h postprandial values of blood glucose (SU 12%, insulin 10%), cholesterol (SU and insulin 25%) was significant after 2-wk of guar treatment compared with the wash-out period. No clinically relevant changes in the safety laboratory parameters were observed during guar treatment. Side effects were observed in 40 of the 93 patients included in the trial. Treatment had to be discontinued in 11% of the patients due to gastrointestinal side effects. On the basis of our results,guar treatment in combination with sulfonylurea and insulin can be recommended for the improvement of carbohydrate and lipid metabolism.

Guar gum and bile: effects on postprandial gallbladder contraction and on serum bile acids in man.

In a randomized cross-over study, 10 healthy volunteers received a fiber-depleted liquid mixed meal alone and, exactly 7 days apart, a combination with 15 g guar gum. Addition of the dietary fiber inhibited emptying of the gall bladder after 30 min to 7 (5-10) ml instead of 4 (3-6) ml (p less than 0.05) and delayed its refilling. Also the postprandial increase in conjugated serum bile acids was prevented by guar gum. The maximal postprandial blood glucose 30 min after ingestion of the meal was reduced from 120 (117-135) mg/dl to 110 (105-119) mg/dl (p less than or equal to 0.05) by guar gum. Serum insulin levels were unaffected by guar gum.--Our data suggest that the addition of guar gum to meals affects enterohepatic circulation of bile acids as well as digestion of carbohydrates.