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M Siess

Publications and source records attributed to M Siess.

59 records · Page 4Linked to original sources

Synthesis and degradation of NAD in guinea pig cardiac muscle: I. Dependence upon the extracellular concentration of nicotinamide and nicotinic acid.

The NAD concentration as well as the 14C-incorporation in NAD and the disappearance of 14C-NAD were studied in spontaneously beating atria of guinea pigs at high and low concentrations of the precursors nicotinamide or nicotinic acid. Atria were incubated in Krebs-Henseleit solution containing 15 mM glucose and the appropriate precursors at 30 degrees C. The control NAD concentration (33 nMol/100 mg w.w.) remained unchanged during a 24-h-incubation time. -20 mM 14C-nicotinamide increased the total NAD about three-fold (90 nMol/100 mg w.w.) after an incubation period of 24 h, with positive effects on the performance. The incorporation rate in 14C-NAD was calculated to be 43.7 nMol/100 mg w.w. . 24 h. The ADPR moiety for the NAD synthesis stemmed from an endogenous pool. Between 5 and 20 mM nicotinamide the increase in the NAD concentration followed an apparent Michaelis-Menten kinetics with a Km of 6.1 mM nicotinamide and a Vmax of 70.92 nMol NAD/100 mg w.w. . 24 h. This can be explained as a new synthesis of NAD by a high concentration of nictoinamide and also by a decreased degradation of NAD, due to inhibition of the glycohydrolase by the high concentration of nicotinamide. The ratio of incorporation and disappearance of 14C-NAD during the 8th and 16th h incubation period was 2:1. After pre-incubation with 20 mM nicotinamide for an 8-h period the NAD concentration decreased to normal values after incubation for 8 h in a nicotinamide free medium. -20 mM 14C-nicotinic acid did not change the total NAD level and no significant incorporation in 14C-NAD could be detected, whereas negative effects on the performance occurred. -10 muM 14C-nicotinamide showed a slight increase in the total NAD concentration (39.7 nMol/100 mg w.w.) and in the 14C-incorporation (4.8 nMol/100 mg w.w.) within 24 h. -10 muM 14C-nicotinic acid seemed here to be the better precursor in this concentration. The NAD concentration increased to 49.8 nMol/100 mg w.w. after a 16 h incubation period and the incorporation in 14C-NAD was 12.1 nMol/100 mg w.w. after an incubation time of 24 h. As consequences of the observed different influences of each precursor on NAD turnover and NAD concentration the pathways of NAD synthesis and degradation must be studied. The importance of an increased NAD level for the energy metabolism of the cardiac muscle under aerobic and anaerobic conditions is discussed.

Animals↗

Some aspects on the regulation of carbohydrate and lipid metabolism in cardiac tissue.

FFA are the main substrate of biological oxidation in cardiac muscle under normal conditions. But it could be shown in man and animal that during heavy exercise there is a shift to preferential oxidation of lactate. During oxygen deficiency in hypoxic or ischemic situations which may occur lightly in distinct areas of hypertrophic hearts after exercise, lactate, alpha-glycerol phosphate and acyl-CoA as well as triglyceride levels in cardiac tissue may increase, whereas FFA are less oxidized. Unoxidized intracellular FFA and acyl-CoA, which are not esterified in a sufficient way to triglycerides, may impair oxidative phosphorylation in mitochondria, the P/O quotient as well as cardiac function perhaps by an interference with Ca++ movements during the contraction cycle. With the examples of anoxia and complete ischemia as the two extreme situations of O2 deficiency some principles of the alteration of cardiac metabolism are pointed out, and furthermore attempts to improve anoxic tolerance of cardiac tissue.

Adenosine Triphosphate↗

The influence of various precursors on the concentration of energy-rich phosphates and pyridine nucleotides in cardiac tissue and its possible meaning for anoxic survival.

A special "anoxia test" was developed with isolated guinea pig atria to test influences on the anoxic energy balance. Adenine, ribose, nicotinic acid or nicotinamide added as precursors to nutrition solutions inhibit the loss of cardiac adenine and pyridine nucleotides during anoxia and improve the energy balance under aerobic and anaerobic conditions in the myocardium.

Adenine↗