Robert Van Reen

Effects of excessive dietary zinc in the rat and the interrelationship with copper.

Abstract 1. 1. The effects of feeding excessive zinc on liver enzymes of the rat were studied. 2. 2. A dietary level of 500–700 mg. per cent zinc resulted in a marked reduction in liver catalase and cytochrome oxidase activities. 3. 3. Copper feeding, along with toxic zinc levels, resulted in an increase of liver catalase and cytochrome oxidase activities to normal values. 4. 4. While copper supplementation influenced the liver enzymes, it had no effect in correcting the growth inhibition produced by zinc.

Sulfide oxidation in rat tissues

Abstract 1. 1. Extracts of rat liver and kidney were shown to catalyze the oxidation of sulfide to thiosulfate. The system responsible for this oxidation contained both a heat-stable and heat-labile component, the former non-enzymic and the latter probably enzymic. Some of the dual characteristics and other properties of the system have been described. 2. 2. The presence of blood masked the heat-labile activity in rat-liver tissue. 3. 3. The greater part of oxygen uptake and sulfide disappearance observable in the system could be accounted for by the thiosulfate formed. 4. 4. Sulfide oxidation to thiosulfate, is most closely associated with the mitochondrial fraction of rat-liver cells. Its relative heat-stability has made possible some purification of the system.

Studies on the influence of sulfur compounds on molybdenum toxicity in rats.

Abstract 1. 1. The influence of methionine, cystine, sodium thiosulfate, and sodium sulfate on molybdenum toxicity in rats was studied. 2. 2. When the sulfur-containing compounds were included in the toxic diet, there was a definite improvement of the enzymatic anomaly observed in molybdenum toxicity. 3. 3. Growth was also improved by the incorporation of these compounds in the toxic diet.

The oxidation of sulfide to thiosulfate by metallo-protein complexes and by ferritin☆

Abstract 1. 1. Metals, metal chelates and metal-protein complexes have been tested as sulfide-oxidizing agents. The conditions for maximal catalytic activity by these systems have been described. 2. 2. At physiological concentrations iron (Fe ++ or Fe +++ ) added to inert protein (crystalline bovine plasma albumin) most closely mimicked the biological sulfide-oxidizing system in rat liver. 3. 3. Ferritin oxidized sulfide to thiosulfate at a rate 45 times greater than did active rat-liver extracts. 4. 4. Some of the catalytic properties of ferritin in sulfide-oxidation have been described and a new physiological function for ferritin has been suggested.

Some aspects of sulfide oxidation by rat-liver preparations.

Abstract 1. 1. The sulfide-oxidizing system in rat liver does not require peroxide for its operation. 2. 2. The existence of a protein-bound intermediate, possibly a thiosulfonate, has been demonstrated. 3. 3. Sulfite may be involved as an intermediate in the in vitro formation of thiosulfate from sulfide. A reaction mechanism has been proposed which accounts for the accumulation of thiosulfate in in vitro systems. 4. 4. Some effects of inhibitors and chelators on the rat-liver system have been described. While 8-hydroxyquinoline stimulated the heat-labile fraction, EDTA stimulated the complete system through its action on the heat-stable fraction.

The influence of excessive dietary molybdenum on rat liver enzymes

Abstract 1. 1. The effects of feeding excessive sodium molybdate on liver enzymes of the rat was investigated. 2. 2. A level of from 400 to 1200 p.p.m. molybdenum resulted in decreased growth and a reduction in food consumption. 3. 3. The copper level of the diet was adequate to maintain normal blood hemoglobin and normal liver catalase and cytochrome oxidase. 4. 4. The most striking alteration in pattern of liver enzymes was a marked increase in alkaline phosphatase activity which could not be correlated with the presence of an enzyme stimulator.

Molybdenum toxicity in the rat.

Summary 1. High levels of dietary molybdenum did not alter ability of rat to acetylate p-aminobenzoic acid or to conjugate benzoic acid with glycine. 2. A depression of food intake and growth was evident within 24 hours after addition of 0.12% molybdenum to the diet. 3. Liver alkaline phosphatase activity was significantly increased in molybdenum-toxic rats whereas the activities of the kidney and intestinal alkaline phosphatases were significantly reduced.

Effect of Starvation on Sulfide Oxidizing System in Rat Liver.

Summary A system in rat liver which oxidizes sulfide to thiosulfate is significantly elevated upon starvation, both in total activity and specific activity. This increase could not be induced in vivo by elevated substrate levels, and was not due to the loss of an inhibitor. Cysteine desulfhydrase levels in rat liver were not materially changed by starvation. These results have been discussed in the light of other findings.

Metabolism in calcified tissues: Pyridine nucleotidases of the rabbit femur

Abstract The destruction of the pyridine nucleotides, DPN and TPN, by preparations from the epiphysial-metaphysial area of the rabbit femur and from the mid-shaft marrow was investigated. The epiphysial-metaphysial preparation was purified by differential centrifugation making use of the fact that the nucleotidases are associated with the insoluble particles. The purified enzyme was quite similar to the beef spleen enzyme in that it had a pH optimum at about neutrality, was inhibited by 10−3M nicotinamide, and split DPN at a faster rate than TPN. Assays on crude preparations from the epiphysis-metaphysis indicated that the breakdown of DPN and TPN was almost entirely at the nicotinamide-ribose linkage whereas the mid-shaft marrow of the young rabbits appeared to have a pyrophosphatase component also. Studies on adult rabbits indicated that the mid-shaft marrow had somewhat higher activity than marrow from young animals. There was little difference in activity between the head of the femur from adult rabbits and the epiphysial-metaphysial area of young animals.

Urolithiasis in the Rat. V. In vivo Dissolution of Calculi.

SummaryUroliths can be formed readily in the weanling NMRI-D rat by feeding a diet containing 15% casein and 4% HMW salt mixture. The calculi are found predominantly in the bladder, sometimes in the bladder and renal pelvis, but rarely in the kidney alone. Calculi formed by the above dietary means can be dissolved in vivo by changing the diet to include more protein and less mineral. It appears that the process of dissolution takes place in a sequence, involving first a demineralization and then dissolution of the matrix. Rats fed diets in the order of calculogenic—protective—calculogenic were found to have an unusually high occurrence of renal calculi without stones being found in the bladder. This may be related to the age of the animals.Summary Uroliths can be formed readily in the weanling NMRI-D rat by feeding a diet containing 15% casein and 4% HMW salt mixture. The calculi are found predominantly in the bladder, sometimes in the bladder and renal pelvis, but rarely in the kidney alone. Calculi formed by the above dietary means can be dissolved in vivo by changing the diet to include more protein and less mineral. It appears that the process of dissolution takes place in a sequence, involving first a demineralization and then dissolution of the matrix. Rats fed diets in the order of calculogenic—protective—calculogenic were found to have an unusually high occurrence of renal calculi without stones being found in the bladder. This may be related to the age of the animals.