Serine Dehydrase Research Articles

Activities of the three ammonia-forming enzymes in the tissues of the brackish-water bivalve Corbicula japonica

1. 1. Activities of the three ammonia-forming enzymes, glutamate dehydrogenase, AMP deaminase and serine dehydrase (SerDH), were measured in tissues of gill, digestive diverticula, mantle and foot muscle of the brackish-water bivalve Corbicula japonica. 2. 2. High levels of SerDH activity were detected in gill and digestive diverticula, while the activity levels of the other two enzymes were low. 3. 3. The result suggests the significance of SerDH in amino acid degradation of this species.

Amino acid metabolism in euryhaline bivalves: regulation of glycine accumulation in ribbed mussel gills.

Glycine levels in isolated ribbed mussel (Modiolus demissus) gill tissue increased slightly and decreased markedly when incubated at high and low salinities, respectively. Low levels of the enzymes involved in the biosynthesis of serine from triose phosphate intermediates, the serine hydroxymethyltransferase, and serine dehydrase were detected in gill tissue homogenates. Experiments using gill tissue incubated with (U-14C)-glycine and (U-14C)-serine indicated interconversion between serine and glycine and transfer of label to alanine, asparate, glutamate, CO2, organic acids, and protein. Glyoxylate was metabolized more slowly than glycine and was probably converted to glycine for catabolism. Studies using (1-14C)-glycine and (2-14C)-glycine with isolated gill tissue and mitochondria indicated that the mitochondrial glycine cleavage enzyme was the major route of glycine catabolism. Metabolic controls activating or inhibiting the glycine cleavage enzyme regulate tissue glycine accumulation and catabolism during hypersalinity or hyposalinity stress.

A Study of the Serine Dehydrase Activity in Alimentary Fatty Liver

A Study of the Serine Dehydrase Activity in Alimentary Fatty Liver

Coordinate control of rat liver lipogenic enzymes by insulin

Recent evidence has established that insulin is required for the dietary induction of rat liver fatty acid synthetase [ Proc. Nat. Acad. Sci. USA 69, 3516 (1972)]. Since other hepatic lipogenic enzymes as well as fatty acid synthetase exhibit coordinate adaptation to nutritional changes [ Advan. Enzyme Regul. 10, 187(1972)], the role of insulin in the dietary induction of these enzymes has been investigated. When a high-carbohydrate, fat-free diet was fed to diabetic rats previously fasted for 48 hr, insulin was shown to be required for the dietary induction of acetyl-CoA carboxylase, citrate cleavage enzyme, malic enzyme, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, fatty acid synthetase, and glucokinase. Activity of serine dehydrase, selected as a model gluconeogenic enzyme, was increased in diabetic rats, whereas insulin treatment reduced the activity of this enzyme during the course of refeeding. The behavior of serine dehydrase was consistent with its gluconeogenic role. The activity of the cytosol isocitrate dehydrogenase did not change during refeeding in the diabetic or insulin-treated diabetic rat. Glucagon, the physiological antagonist of insulin, inhibited the increase in activity of each of the lipogenic enzymes requiring insulin for induction. Our results indicate that insulin is required for the coordinate regulation of the lipogenic enzymes of mammalian liver.

The synthesis of taurine from sulfate. IV. An alternate pathway for taurine synthesis by the rat.

SummaryThe rat is capable of synthesizing taurine from sulfate. The enzymatic pathway appears to be similar to that in chick liver which utilizes l-serine and activated sulfate (PAPS). The enzymes which catalyze this reaction sequence appear to be the same as those for the chick liver system, serine dehydrase, PAPS-sulfotransferase, and cysteic acid decarboxylase.

The synthesis of taurine from sulfate. 3. Further evidence for the enzymatic pathway in chick liver.

SummaryThe purpose of this research was to determine the enzymatic pathway for the synthesis of taurine from inorganic sulfate in chick liver. The enzymatically active proteins were obtained in the supernatant fraction from an ammonium sulfate precipitate (0.7 saturation) of chick liver homogenate using carboxymethylcellulose (CMC)-ion exchange chromatography. Experiments designed to ascertain the acceptor of the sulfate from 3′-phosphoadenosine-5′-phosphosulfate (PAPS) indicated that serine had the highest activity. Further, pyridoxal phosphate-dependent serine dehy-drase activity was required in the reaction utilizing serine to form taurine. The formation of taurine was preceded by the intermediate being converted to enzyme-bound cysteic acid. Inhibition studies indicated that PAPS-transferase, serine dehydrase, cysteic acid decarboxylase activities were required for this reaction, as well as a sulfhydryl requirement.

Time course of enzyme adaptation. 3. Periodic and nonperiodic responses of rat liver enzyme activities to diets in meal-fed rats.

Enzymes associated with carbohydrate and amino acid metabolism as well as other liver constituents were studied in rats meal-fed, daily for 60 min, diets consisting of corn oil, salt, and vitamins plus 75% carbohydrate and 15% casein or a 90% casein diet. Relative liver size and the levels of liver glycogen and total and soluble liver protein were subject to periodic variation after the ingestion of a meal. They reached maximums about 6–12 h after the meal and then declined. In the rats fed the 90% casein diet the onset of increases was delayed after the first meal.The activity of glucose-6-phosphatase was increased by a fructose diet and the high-protein diet, but no periodicity was observed. The activities of fructose-1, 6-diphosphatase, dihydroxyacetone kinase, and malic enzyme were not subject to periodic variation, and these enzymes were not increased by the fructose or high-protein diets. Serine dehydrase activity was increased by the high-protein diet, but the question of periodicity cannot be resolved with the available data.The tyrosine–α-ketoglutarate transaminase activity in rats fed a 75% glucose – 15% casein diet was subject to periodic variation. Maximum activity occurred just before feeding, and minimum activity 12 h after feeding. In the rats fed the 90% casein diet the activity of the enzyme was considerably increased, and was already maximum 3 h after the meal. The activity then decreased to a relatively high minimum 12 h after the meal, at which time it began to increase again.The activities of pyruvate kinase, glucose-6-phosphate dehydrogenase, and phosphohexose isomerase were all subject to periodicity in the glucose-fed rats. In the rats fed the high-protein diet, there was a periodic response in activity of both pyruvate kinase and glucose-6-phosphate dehydrogenase after the first meal; but enzyme activity remained minimum after the second meal. Glucose-6-phosphate dehydrogenase and phosphohexose isomerase activities were increased after three meals of the fructose diet, and were higher than in glucose-fed rats even 24 h after a meal. Maximum activity of these three enzymes occurred 12 h after the meal. There was only small periodicity in the activity of glutamic–pyruvic transaminase. The activity of this enzyme was increased by the high-protein diet and also by the high-fructose diet, although the latter effect was only temporary. The possible importance of certain types of adaptations in meal-fed rats was discussed in connection with physiological requirements.

On the Relationship between Food Composition and Serine Dehydrase Activity in Rat Liver

On the Relationship between Food Composition and Serine Dehydrase Activity in Rat Liver

Induction of Hepatic Enzyme Synthesis in Vivo by Adenosine 3',5'-Monophosphate

Abstract The N6,O2'-dibutyryl analogue of cyclic adenosine 3',5'-monophosphate (dibutyryl cyclic AMP) elevates the level of hepatic tyrosine-α-ketoglutarate transaminase (l-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5) some 3- to 6-fold in intact and adrenalectomized rats. The response of this enzyme is more rapid to dibutyryl cyclic AMP than to any other inducer of the transaminase. Hourly injection of dibutyryl cyclic AMP can maintain the elevated transaminase level for at least 5 hours. The rate of synthesis of tyrosine transaminase, as measured by an isotopic-immunochemical procedure, is enhanced by treatment with dibutyryl cyclic AMP. There is no detectable effect of dibutyryl cyclic AMP on the synthesis of total soluble proteins, however. Combinations of dibutyryl cyclic AMP and hydrocortisone produce additive or, in some cases, synergistic increases in transaminase activity, but the responses to combinations of dibutyryl cyclic AMP and either glucagon or insulin are not additive. Two other soluble liver enzymes, P-enolpyruvate carboxykinase (GTP:oxaloacetate carboxy-lyase transphosphorylating, EC 4.1.1.32) and serine dehydrase (l-serine hydro-lyase, EC 4.2.1.13) are also elevated by treatment of intact rats with either dibutyryl cyclic AMP or glucagon, but another, tryptophan pyrrolase (l-tryptophan:oxygen oxidoreductase, EC 1.13.1.12, tryptophan oxygenase), is not affected by either agent. Hydrocortisone induces both the transaminase and pyrrolase 3- to 5-fold but the steroid has no effect on either the carboxykinase or the dehydrase. The results support the view that cyclic AMP is the intracellular mediator of the action of glucagon on hepatic enzyme synthesis.

Adaptation of the Weanling Rat to Diets Containing Excess Methionine

High levels of L-methionine in the diet of weanling rats induced a severe growth depression for up to 5 days whereupon weight gain at a near normal rate occurred despite the animals’ consumption of the same excess amino acid diet. Alterations in hepatic levels of cystathionine synthase, cystathionase, cysteinesulfinate carboxylase and serine dehydrase occurred concurrent with changes in the growth rate. Alterations in tissue levels of methionine and its metabolites directly paralleled enzymatic changes. From these studies we conclude that the rat adapts to excess dietary methionine by altering its metabolic response to the amino acid.

Activities of cystathionase, cysteine sulphinic acid decarboxylase and serine dehydrase in the liver of tumour-bearing rats.

Dans le foie de rats porteurs de tumeurs (epitheliome de Guerin et sarcome de l'estomac), les activites de la cystathionase, de la decarboxylase de l'acide cysteine sulfinique et de la serine dehydrase sont considerablement diminuees: cette diminution est de l'ordre de 50%, 15 jours apres implantation de ces tumeurs. Si a ce moment le sarcome (qui ne provoque pas de metastases) est chirurgicalement extirpe, on observe une restauration des activites enzymatiques qui, apres 15 jours, est totale pour la cystathionase et tres significative pour la decarboxylase.

Effect of adrenalectomy and hypophysectomy on responses of rat liver enzymes to high-fructose diets.

The effect of dietary fructose on the activities of a number of enzymes was studied in normal, adrenalectomized, and hypophysectomized male Sprague–Dawley rats. The effect of feeding a high-fructose diet on relative liver size, soluble protein, glycogen, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, phosphoglucomutase, glyceraldehyde-3-phosphate dehydrogenase, and glucose-6-phosphatase was not appreciably altered by endocrinectomy. It appears, therefore, that the fructose effect on these rat liver constituents is not mediated by adrenal or pituitary hormones, although endocrine function may influence enzyme activity. The enzymes which were not particularly affected by either endocrinectomy are those associated with the metabolism of phosphorylated intermediates.The fructose diet increased the activities of L-α-glycerophosphate dehydrogenase and lactic dehydrogenase to a greater extent after endocrinectomy; therefore, an inhibition of the fructose effect in normal animals by endocrine function was postulated. The effect of feeding fructose on the activities of the pentose-phosphate-metabolizing enzymes and glutaminase was abolished by hypophysectomy. In this case it was postulated that pituitary function is required for the fructose effect as a permissive agent. The fructose-mediated increases of malic enzyme and uridine-diphosphoglucose dehydrogenase were diminished in magnitude after endocrine removal, but not abolished.The activities of the urea-cycle enzymes, transaminases, and serine dehydrase were not increased by fructose feeding. The relationship between the fructose effect and endocrinectomy appeared to be complicated in the case of malic dehydrogenase and fumarase.

A possible method for estimating hormone effects on enzyme synthesis

The activities of four rat liver enzymes (glucose 6-phosphate dehydrogenase, serine dehydrase, glutamic-pyruvic transaminase, and glutamic-oxaloacetic transaminase) were studied in a 90% glucose to 90% casein or a 90% casein to 90% glucose dietary change in the absence and in the presence of exogenous hydrocortisone. From the rates of increases or decreases in enzyme activities the rates of synthesis and values of half-lives of these enzymes were estimated. Comparison of these parameters in the presence and absence of exogenous hydrocortisone indicate that the hormone increases the activity of glucose 6-phosphate dehydrogenase (in the glucose to protein dietary change but not in the reverse dietary change) and glutamic-pyruvic transaminase by increasing the rates of synthesis of these enzymes without altering their rates of degradation. The half-lives of these enzymes were not altered by dietary protein. Serine dehydrase activity was increased by hydrocortisone and it appeared that while protein only increased the rate of synthesis of this enzyme, hydrocortisone increased its half-life and rate of synthesis. The activity of glutamic-oxaloacetic transaminase was increased by dietary protein and also by the hormone. The half-life of the enzyme was smaller in protein-fed or hydrocortisone-treated animals; the hormone apparently mimicking the effect of dietary protein. The utility of the method used for evaluating hormone effects on enzyme activities were discussed with respect to applicability, rapidity, and ease especially in cases when antibody precipitation is not practical.

Location and properties of serine dehydrase in the chick

1. 1. Serine dehydrase activity in the chick is higher in kidney than in liver. Kidneys may have in birds a more important role in protein catabolism than they have in mammals.

Reversibility of the thyroxine effect on rat liver glutamic-pyruvic transaminase and serine dehydrase by dietary supplementation of vitamin B 6

Reversibility of the thyroxine effect on rat liver glutamic-pyruvic transaminase and serine dehydrase by dietary supplementation of vitamin B 6

Dietary Effects on Rat Liver Enzymes in Meal-fed Rats

The effects of dietary changes and starvation were studied in meal-fed, male rats of the Sprague-Dawley strain following a training period of 2 weeks and a period of protein deprivation of 4 days. A 90% casein diet increased the activities of the enzymes glucose 6-phosphatase, glucose 6-phosphate dehydrogenase, serine dehydrase, tyrosine-α-ketoglutarate transaminase, glutamic-pyruvic transaminase and glutamic-oxaloacetic transaminase 24 hours after the meal. Serine dehydrase and glutamic-oxaloacetic transaminase activities were further increased in animals killed 48 hours after the protein meal. An increase in the activity of serine dehydrase was also observed in rats killed 48 hours after their last protein-free meal. The feeding of diets which contained both carbohydrate (either glucose or fructose) and casein, increased glucose 6-phosphate dehydrogenase and malic enzyme activities to a greater extent than the 90% casein diet, but the increases in transaminase activities were less than those obtained by feeding the 90% casein diet. Serine dehydrase activity was not increased by a 65% carbohydrate diet and was increased only slightly by diets containing 57.5% casein plus 32.5% carbohydrate. Tyrosine-α-ketoglutarate transaminase activity was increased by this latter diet almost as well as by the 90% casein diet. The inducing effect of carbohydrates on enzyme activities was observable, even if the test diets contained considerable amounts of protein, whereas the inducing effect of protein was considerably decreased by even a moderate amount of carbohydrate.

Time-Course of Changes in Rat Liver Enzyme Activities after Initiation of a High Protein Regimen

The effects of feeding a high protein diet to rats previously adapted to a high carbohydrate diet containing adequate protein was studied in male Sprague-Dawley rats. The high carbohydrate diet was found to stimulate growth which was not augmented noticeably by feeding the high protein diet. Liver protein reached maximal values one day after the dietary change, whereas relative liver size values remained relatively constant. The glycogen content of liver was minimum one day after the dietary change which was followed by relatively higher and constant values. The enzymes studied could be divided into 2 groups based on the pattern of change in enzyme activity after the dietary shift. In one group, which includes fructose 1,6-diphosphatase, glucose 6-phosphatase, glutamic-oxaloacetic transaminase, glutamic-pyruvate transaminase, serine dehydrase and tyrosine-α-ketoglutaric transaminase, enzyme activity increased with time. Furthermore, the activity of these enzymes increased without a lag, with the exception of fructose 1,6-diphosphatase, which increased in activity only after a one-day delay. In the second group, which includes L-α-glycerophosphate dehydrogenase, glucose 6-phosphate dehydrogenase, pyruvate kinase and malic enzyme, enzyme activity was decreased by feeding the high protein diet, except that the activities of pyruvate kinase and malic enzyme were temporarily increased one day after the dietary change. The physiological significance of a lag in enzyme induction, when such occurs, and a possible mechanism for the transitory induction of pyruvate kinase and malic enzyme by the high protein diet are discussed.

Effects of Casein Hydrolysate on the Induction and Regulation of Tyrosine-α-Ketoglutarate Transaminase in Rat Liver

A several fold increase in the activity of tyrosine-α-ketoglutarate transaminase occurs in intact or adrenalectomized rats following treatment with an enzymatic hydrolysate of casein, whereas tryptophan pyrrolase is unresponsive to this treatment. Doses of tyrosine, tryptophan, or the combination of these amino acids equivalent in amount to those contained in an effective dose of casein hydrolysate did not produce a rise in tyrosine transaminase activity. The effect of casein hydrolysate is inhibited by actinomycin D or cycloheximide, indicating that the synthesis of new RNA and protein is associated with the response of tyrosine transaminase to casein hydrolysate. Additive and, in some cases, synergistic effects on tyrosine transaminase are observed when casein hydrolysate and hydrocortisone are given together or sequentially. In contrast to the response of this enzyme, no additive effect on tryptophan pyrrolase or serine dehydrase occurs when 1 g of casein hydrolysate is given at the same time as a large dose of hydrocortisone. Treatment of adrenalectomized rats with casein hydrolysate, 4 or 8 hours after they were treated with hydrocortisone, stimulates a marked further increase in the activity of tyrosine transaminase. In intact rats, tyrosine transaminase shows a synergistic response to casein hydrolysate when it is given concomitantly with a small dose of hydrocortisone; under these conditions tryptophan pyrrolase is also responsive, but this effect appears to be due to tryptophan stabilization of the enzyme against degradation. When a low dosage of hydrocortisone is administered to intact rats, tryptophan pyrrolase, but not tyrosine transaminase, shows an increase in activity. On the other hand, of these two enzymes, only the transaminase responds to casein hydrolysate. Each of these treatments stimulates the incorporation of orotic acid-6-14C into liver RNA to about the same extent, indicating either that this is a selective effect or that factors in addition to new RNA synthesis are involved in the induction of these enzymes.

Comparative Effects of Actinomycin and Ionizing Radiation on Enzyme Synthesis in Mammalian Cells in Vivo

Studies using actinomycin D or ionizing radiation have done much to elucidate our knowledge of the control of genetic expression in mammalian tissues. However, little effort has been made to correlate the findings with one inhibitor with those obtained with the other. In the regenerating liver system in rats, DNA synthesis as well as the increase in DNA polymerase resulting from the operation is inhibited by actinomycin and ionizing radiation when the inhibitor is administered within the first 15 hours after the operation or, in the case of radiation, sometime before. If these substances are given after this time, no effect is noted on these processes. Studies on the control of enzyme synthesis in mammalian cells have shown that hormonal induction of enzyme synthesis is inhibited by actinomycin, whereas substrate or dietary induction of several enzymes show different or no effects. The induction of serine dehydrase in rat liver is initially sensitive and later resistant to the effects of actinomycin as we...

Effect of thyroid hormones on metabolism. II. The effect of adrenalectomy or hypophysectomy on responses of rat liver enzyme activity to l-thyroxine injection.

Many enzyme activities which were increased by hydrocortisone were decreased by adrenalectomy. This effect was more apparent with enzymes related to amino acid metabolism than those related to carbohydrate metabolism. The latter, although significantly increased by hydrocortisone, did not show marked decreases after adrenalectomy. Hypophysectomy decreased the activities of many enzyme systems associated with carbohydrate metabolism more drastically than did adrenalectomy. The results with the enzymes related to amino acid metabolism were not as clear. Several of these were decreased to a greater degree after hypophysectomy than after adrenalectomy. In contrast, several enzymes were also increased above the control values after hypophysectomy. Adrenalectomy was particularly efficient in decreasing the activities of several transaminases, and hypophysectomy had a marked effect upon decreasing TPN+-linked enzyme systems.The response of several enzymes to L-thyroxine injections was decreased in magnitude or eliminated after adrenalectomy. This was particularly true for enzymes associated with carbohydrate metabolism. Several enzymes increased by L-thyroxine in intact animals were actually decreased in adrenalectomized rats after this treatment. This was particularly true for serine dehydrase and glutamic–pyruvic transaminase. These results are strongly suggestive of a thyroxine–adrenal interaction in the intact animal. Hypophysectomy had a similar effect on enzyme responses to L-thyroxine, with the exception of glutaminase. Therefore, many of the effects of hypophysectomy may actually be related to a lack of adrenal function. It was observed that the removal of the adrenal had similar effects on responses of enzyme activity after thyroxine treatment, as did pituitary removal. Certain of the enzymes were decreased to a greater extent by hypophysectomy, and others were actually increased in activity after removal of the pituitary. It therefore appears that in many enzyme systems there is a complete requirement for the pituitary and (or) adrenals for a L-thyroxine effect on enzyme activity. In other enzyme systems the dependence appears to occur but does not appear to be complete.