Jacob Sacks

Effect of Hyperthyroidism on Distribution of Adenosine Phosphates and Glycogen in Liver.

Summary Chronic hyperthyroidism induced in guinea pigs by daily injection of thyroxin has no effect on concentrations of ATP, ADP, and AMP in the liver. This finding gives no support to the postulate that thyroxine produces its metabolic effects by dissociating phosphorylation from oxidation. Reduction in glycogen content of liver that results from chronic hyperthyroidism is entirely in the fraction extractable by TCA.

Free and bound nucleotides in frog and mammalian muscle

Abstract The Atp of muscle can be separated into three fractions by differential extraction of the powered frozen muscle. A fraction firmly bound to protein, equivalent to 5–6 moles/mole of myosin in bullfrogs, and to more than twice this amount in cats, is considered to act as the bridge between myosin and actin necessary to account for the structure of resting striated muscle shown by the electron microscope. A second fraction is also considered to be protein-bound, but, fairly readily dissociable therefrom. More ATP is found unbound to protein in bullfrog than in cat muscle. The ADP in both species is essentially all protein-bound and is present in an amount equivalent to the 1 mole/mole of F-actin monomer that has been found for the isolated protein. Tetanic contraction of 15 seconds duration does not lead to any significant change in relations between free and bound nucleotide derivatives.

Bound adenosine diphosphate and adenosine triphosphate in resting and contracting muscle

Abstract Resting muscle contains bound ADP in sufficient quantity to indicate that all the actin is present in the fibrous form, and that the binding in vivo is present to the same extent as has been found with the isolated protein. There is sufficient bound ATP to support the hypothesis of multiple binding sites to myosin. Tetanic contraction does not lead to any shifts between free and bound ADP or ATP. It is postulated that these multiple binding sites of ATP to myosin may act as bridges between the myosin and actin filaments which the electron microscopy studies have shown to be present in muscle. It is also postulated that these multiple binding sites of ATP to myosin prevent the change in conformation about the active center of the ATPase portion which would be necessary for the catalytic action to be manifested.

Hexosephosphate formation and the regulation of glycolysis in muscle

Abstract The steady state concentrations of the hexosephosphates, and tracer data with 32 P i suggest that the formation of glucose-6-phosphate in resting muscle takes place predominantly from the glucose and P i present in the extracellular phase, and that the phosphorylase system is essentially inactive under these conditions. The rate of glycogenolysis in tetanic contraction is such that it is adequate to support the very high rate of lactic acid formation under these extreme conditions. The apparent primary rate-limiting step in glycolysis is the phosphohexose isomerase reaction, both in resting muscle and in contraction. The activity of phosphofructokinase in resting muscle is sufficient so that this reaction is not rate-limiting; however, the activation of this enzyme in tetanic contraction is not necessarily adequate to the situation, and this reaction may then become rate-limiting. The tracer data indicate that the formation of fructose-1,6-diphosphate in contraction may take place by some mechanism other than the phosphofructokinase reaction.

Effect of alloxan diabetes on the de novo synthesis of the adenosine phosphates of liver

Abstract With formic acid-C 14 as the tracer, it was found that the de novo synthesis of ADP and ATP takes place more rapidly in the liver of the normal rat than the de novo synthesis of AMP. Possible explanations of the discrepancy between these findings and those to be anticipated from the known enzymic mechanisms are offered. It has also been found that in the liver of the alloxan diabetic rat there is a marked decrease in the rate of de novo synthesis of ATP. This limitation of the rate of ATP synthesis, which itself involves many ATP-dependent reactions, may account for the over-all diminished rate of synthetic reactions in diabetes.

FREE AND BOUND ORTHOPHOSPHATE AND PHOSPHOCREATINE IN MUSCLE.

Abstract The use of ethanol at low temperature as deproteinizing medium reveals the presence of some bound phosphocreatine as well as of bound Pi in resting muscle. The amount of bound Pi in muscles of frogs and rabbits is comparable to that bound by myosin isolated from these species, but the amount in cat muscles is significantly greater. The free Pi content is of the order of 3–5 μmoles per gram, and the total of free plus bound Pi is essentially the same whether neutral or acidic deproteinizing agents are used. The data obtained do not give any evidence to support the postulate that muscle contains a P compound more labile to acid than is phosphocreatine.