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Influence of oral contraceptives, pyridoxine (vitamin B6), and tryptophan on carbohydrate metabolism.

Carbohydrate metabolism and vitamin-B6 status were assessed before and after pyridoxine administration in 46 women taking combined oestrogen-progestagen oral contraceptives (O.C.). 18 women had evidence of tissue depletion of vitamin B6, although all the women had abnormal tryptophan metabolism, including increased urinary xanthurenic acid (X.A.) excretion. In the women with vitamin B6 deficiency, administration of this vitamin caused elevation of fasting blood-pyruvate levels, and reduction in plasma glucose, insulin, and blood-pyruvate responses after an oral glucose load. These changes in carbohydrate metabolism were not found in the 28 non-vitamin-B6-deficient women. These results indicate that carbohydrate intolerance in women on O.C. is unlikely to be mediated by the formation of a complex of X.A. with insulin, as has formerly been proposed. Since the synthesis of the tryptophan metabolite quinolinic acid, an inhibitor of the heptaic enzyme phosphoenolpyruvate carboxykinase, may be enhanced by the administration of pyridoxine, it is suggested that this metabolite might be the important factor in the improvement of glucose tolerance in the vitamin-B6-deficient women. This conclusion is supported by the improvement in glucose tolerance observed in 6 women on O.C. and in 4 patients with glucocorticoid excess who were not vitamin-B6 deficient, when they were given tryptophan to augment the synthesis of quinolinic acid.

Adult

Carbohydrate metabolism of the lens depending on age.

Interpretation of factor analysis of 18 metabolic parameters of the bovine lens leads to the determination of the following criteria of lens metabolism: Factor 1: Biologic aging of the lens 33.9%; Factor 2: Glycolysis regulation 17.7%; Factor 3: Topography of lens metabolism 8.7%; Factor 4: Regulation of fructose breakdown 7.9%; Factor 5: Substrate depot 6.6%; Factor 6: Kinases 6.3%. These results could partly be experimentally verified. This interpretation of factor analysis has been an attempt to fit biochemical processes to formal statistical parameters. There was no indication that any of the variables under investigation were indendently responsible for the age dependend changes. However, the set-up made evident that rather complex biochemical influences of different intensity bring about the observed aging phenomena. It may be assumed that on or the other of these variables acts as a "triggering mechanism". Age related disturbances in the biochemical balance may be initiated by the glycolysis regulation factor, the importance of which is expressed by its high portion of 17%. Here changes in the ratio of reduced and oxydized coenzymes may act as a "triggering mechanism" (26, 30). Topography of lens metabolism, carbohydrate breakdown via metabolic pathways, the presence of substrate depots, and the internal regulation of the kinases are, according to their portion in factor loading, of about equal importance with respect to aging processes, however, factors 1 and 2, with a 50% portion, must be given precedence in any consideration. Factor 1, interpreted as "biological lens aging", yields about 1/3 of the information on the age influence on lens metabolism. This factor stands independent in being loaded by lens weight, which is the accepted age representative. However, lens weight means protein as well as the process of protein synthesis. It may be assumed that this factor represents a connective link between protein and carbohydrate metabolism, since it is well known that changes in protein belong to the most remarkable age disturbances (31,32), and that the quality of the proteins is dependent on the period of its synthesis (18,33).

Alanine Transaminase

[Activity of carbohydrate-metabolizing enzymes and content of carbohydrate and nitrogen compounds in muscles of young cattle depending on breed and sex].

The activity of glycolysis and glyconeogenesis enzymes, content of carbohydrate and nitrogen compounds were studied in muscles of 15-month cattle of different sex of the black-piebald breed and its crosses with bulls of two meat breeds Hereford and Limousine. In the muscles of bulls the activity of phosphoglucomutase, phosphohexoisomerase, aldolase and fructose-1,6-diphosphatase is considerably higher (except of the activity of phosphoglucomutase and phosphohexoisomerase in the muscles of pure-bred black-piebald animals for which difference is not statistically reliable) and the content of glycogen, glucose, fructose, lactic acid, free and phosphorylated pentoses of nonadenylic compounds is essentially lower than in the muscle tissue of heifers of analogous breed groups. A higher activity of carbohydrate metabolism enzymes (especially aldolase and fructose-1,6-diphosphate) and a higher content of total pentoses, the adenylic system pentoses, ATP phosphorus in the muscles of the cross Limousine and Hereford bulls and Limousine heifers as compared to the pure-bred black-piebald animals of the corresponding sex coincide with a greater increase in the muscular tissue and more intensive synthesis of proteins in it. A considerably lower level of glycogen, glucose, fructose and a relatively high activity of carbohydrate metabolism enzymes in the muscles of cross young cattle show that disintegration of these carbohydrates is in excess of their synthesis, that is due to an increase in the energy demand connected with a more intensive synthesis of proteins in the muscular tissue. Therefore, in the authors opinion the performed kill of the cross Limousine and Hereford bulls as well as Limousine heifers, is somewhat untimely and unreasonable. At the same time the activity of all the studied enzymes in the muscles of the cross Hereford heifers, vice versa, is considerably lower as compared to the black-piebald heifers and coincides with a low gain in live weight and muscular tissue, a more rapid accumulation of glycogen and lipids and a more delayed--of proteins in the muscular tissue, that evidences for their early maturity. Therefore the further raising of the cross Hereford heifers in the farm for obtaining meat is economically less profitable. The data obtained give grounds to recommend determination of the activity of carbohydrate metabolism enzymes, especially of aldolase and fructose-1,6-diphosphate, as a test for checking the muscular tissue growth and for prognosing the meat productivity in the growing pure-bred and cross young cattle of different sex.

Adenosine Triphosphate

Metabolic implications of distal atrophy. Carbohydrate metabolism in centronuclear myopathy.

Centronuclear myopathy, like myotonic dystrophy, is characterized by muscle wasting and type 1 fiber atrophy. To determine whether this disorder might include a derangement in carbohydrate metabolism similar to that in myotonic dystrophy, 3 comparably wasted patients with centronuclear myopathy, myotonic dystrophy, and neurogenic atrophy were investigated. The patient with centronuclear myopathy had mild glucose intolerance and hypoinsulinemia after oral glucose ingestion in bold contrast to the normal glucose tolerance and hyperinsulinemia observed in the myotonic dystrophy patient. No abnormality was seen in oral glucose tolerance in the patient with neurogenic atrophy, and all 3 patients had normal insulin tolerance. Forearm insulin infusion demonstrated normal stimulation of muscle glucose uptake in the patients with centronuclear myopathy and neurogenic atrophy in contrast to the markedly diminished response to insulin seen in the patient with myotonic dystrophy. These data indicate that neither distal wasting or type 1 fiber atrophy are responsible for the abnormalities in carbohydrate metabolism in myotonic dystrophy.

Adult

Hepatic metabolism of genetically diabetic (db/db) mice. I. Carbohydrate metabolism.

Hepatic carbohydrate metabolism in genetically diabetic mice (db/db) and their normal littermates has been studied. In db/db mice, body water was below normal and declined with age. The liver of db/db mice was abnormally large in relation to the metabolic mass of the body at all ages studied. In db/db mice, hepatic glycogenolysis, glycogen synthesis, glycogen synthetase, and phosphorylase were markedly increased. Gluconeogenesis from alanine or lactate in perfused livers of db/db mice was greater than normal per 100 g body water. Activities of fructose-1, 6-biophosphatase, glucose-6-phosphatase, glucokinase + hexokinase, and pyruvate kinase were elevated in livers of db/db mice. Diabetic mouse livers perfused with lactate showed a markedly reduced concentration of P-enolpyruvate and clear "forward crossover" between fructose-1, 6-P2 and fructose-6-P. In vivo glucose clearance, measured with [3-3H]glucose, in db/db mice was 170% that of normal mice. Data presented indicate that in livers of db/db mice: 1) glucose production is elevated prior to hyperglycemia, 2) glycogen turns over more rapidly, and 3) glycolytic and gluconeogenic enzymes are elevated paradoxically. These abnormalities are discussed from the viewpoint of their etiology.

Animals

Carbohydrate metabolism in cardiovascular disease.

Carbohydrate metabolism is temporarily disturbed in acute myocardial infarction. The degree of hyperglycaemia and failure of response of insulin appears to be related to the severity of the infarction. The underlying hormonal changes probably include increased secretion of catecholamines and of glucagon. Circulating free fatty acids (FFA) are generally increased by the same metabolic and hormonal factors which promote glucose intolerance. In the zone of developing infarction in the heart, there is a complex metabolic situation with glucose metabolism both being accelerated and inhibited by different factors. Continued uptake of FFA is associated with intracellular accumulation of activated long-chain FFA, acyl CoA, which tends to inhibit mitochondrial metabolism. The metabolism of glucose is thought to be beneficial and that of FFA detrimental to the infarcting tissue. Thus the glucose intolerance and the high circulating FFA occurring as part of the general metabolic response to myocardial infarction, are thought to be harmful to the ischaemic tissue. Increased provision of glucose by dichloroacetate, and inhibition of FFA metabolism by nicotinic acid analogues decrease the extent of experimental infaraction, while glucose--insulin--potassium and propranolol act both by increasing glucose uptake and decreasing that of FFA. Glucose intolerance is also common in peripheral vascular disease. The reasons for this are obscure. However, the alterations in circulating insulin concentration which accompany this intolerance may be involved in the development of arterial lesions either directly through an effect on arterial wall synthesis or indirectly through an effect on circulating lipid levels. Defects may also be found in arterial wall mucopolysaccharide or sorbitol metabolism. The role of sex hormones and catecholamines remains speculative. At present the most cogent view is that in peripheral vascular disease a multi-hormonal disorder exists which may be contributing to the development of arteriosclerosis.

Acute Disease

Hybrid genome assembly and phenotypic assays reveal carbohydrate metabolism diversity in Lacticaseibacillus strains.

Investigation of carbohydrate metabolism in lactic acid bacteria is essential for the rational selection of strains for fermentation processes, particularly in emerging applications involving non-conventional substrates or building of synthetic microbial consortia. However, establishing robust genotype-phenotype relationships remains challenging, as gene presence alone often fails to explain observed metabolic traits without considering the genomic context and regulatory architecture. In the present study, we combined hybrid genome assembly (Illumina and Oxford Nanopore) with high-throughput phenotype profiling (Biolog GENIII and PM2A) to investigate carbohydrate utilization in five Lacticaseibacillus strains. Phenotypic assays revealed clear intra- and inter-specific variability in substrate utilization. We therefore investigated whether such differences could be attributed to the organization and regulatory context of carbohydrate-associated loci, rather than to gene presence alone. Functional annotation based on COG and CAZyme databases revealed candidate genomic regions potentially involved in carbohydrate metabolism. Comparative analysis between predicted and experimentally observed substrate usage highlighted specific loci associated with carbohydrate utilization profile. The trehalose (tre) operon was conserved across all strains, while at least two distinct cellobiose-associated loci were detected in each genome. Despite the presence of these loci, L. paracasei strains were unable to metabolize cellobiose, a phenotype likely linked to the presence of a downstream TetR-type transcriptional repressor within the cellobiose (cel) operon. Additionally, a genomic region uniquely found in L. rhamnosus strains was associated with gentiobiose utilization, consistent with phenotypic observations. Overall, these findings highlight the importance of integrating phenotypic validation with complete genome context to support the identification of candidate structural and regulatory determinants of carbohydrate utilization in lactic acid bacteria. KEY POINTS: • Phenotype microarrays reveal metabolic traits of interest in isolated strains. • Regulatory context is key to understanding carbohydrate metabolism differences. • Basis of subspecies-dependent cellobiose metabolism in L. paracasei is provided.

Carbohydrate Metabolism

Skeletal muscle characteristics and carbohydrate metabolism after glucose loading in hypokalaemic periodic paralysis.

A prolonged glucose load was administered to four patients with hypokalaemic periodic paralysis and four healthy control sujbects. Muscle ATP and CP concentrations as well as lactate dehydrogenase, hexokinase and phosphorylase activities were similar in those two groups, but succinate dehydrogenase was approximately 50% higher in the control muscles. Muscles fibre composition was almost identical in the two groups, whereas patients had a higher degree of capillarization. Complete muscle weakness was produced in all patients, accompanied by hypokalaemia. Glucose loading resulted in elevated insulin levels and a minor rise in blood glucose level was seen in the patients compared to the control subjects. Glucose loading decreased hexokinase activity in controls, but increased this in the patients. At similar times, muscle and blood lactate levels and blood pyruvate values were generally higher in the patients over the course of the experiment. Initial glycogen concentrations were higher in patients, but glucose loading did not result in greatly increased glycogen values. These data suggest that patients with hypokalaemic periodic paralysis have an enhanced metabolism of carbohydrates and that insulin seems to be an important factor leading to the onset of muscle weakness.

Adenosine Triphosphate

Carbohydrate metabolism of malarial parasites.

The evidence for the pathways involved in the metabolism of carbohydrates by malarial parasites is critically reviewed. In all species studied, glucose is catabolized mainly by glycolysis with little participation of the pentose-phosphate pathway. It has not been proved conclusively that there is a functioning citric acid cycle in the intraerythrocytic stages of avian plasmodia, nor is it certain that these stages of any malarial parasites use oxygen.

Animals

Investigation of carbohydrate metabolism and somatomedin in osteosarcoma patients.

Altered carbohydrate metabolism associated with fibrosarcomas and chondrosarcomas has been well-documented in past literature. This report describes abnormal carbohydrate metabolism in 2 osteosarcoma patients, and abnormalities in growth hormone and somatomedin serum levels. Experimental evidence is presented showing in vitro suppression of osteosarcoma tumor cell proliferation by 17 beta Estradiol. Estrogen inhibition of linear bone growth, cartilage proliferation, and somatomedin is discussed with reference to possible estrogen therapy in osteosarcoma.

Adolescent

[Carbohydrate metabolism and endogenous hyperlipemia].

The state of carbohydrate metabolism was studied under conditions of endogenous hyperlipemia induced by triton WR-1339. The data obtained testify to the fact that administration of triton WR-1339 to experimental animals intensifies lipogenesis from carbohydrates, that is confirmed by a decrease in the glycogen amount in the liver and by an activation of the pentose-phosphate pathway of carbohydrate oxidation which is important for cells intensely synthetizing fatty acids. Thus, there is a relation between disturbances in carbohydrate metabolism and development of hyperlipemia induced by the triton.

Animals

Carbohydrate metabolism and insulin resistance in myotonia dystrophica.

Carbohydrate metabolism was studied in fourteen patients with myotonia dystrophica (MD) using oral glucose, fructose and galactose tolerance tests. Insulin responses to tolbutamide, glucagon, arginine and leucine were determined and insulin resistance was measured with exogenous iv insulin. Glucose tolerance was impaired in twelve of the four teen subjects while hyperinsulinism was found in all patients studied. Insulin response to the various substances was excessive. The insulin tolerance test revealed insulin resistance in all patients and this generally correlated well with the degree of hyperinsulinism to provocative tests. Serum galactose levels after an oral load were much lower in MD compared to normal subjects and were associated with a correspondingly greater rise in glucose, indicating an increased conversion of galactose to glucose. A similar response to oral galactose was found in diabetics. The hyperinsulinism seen with the fructose and galactose tests corresponded well to the rise in glucose during the test. Urinary sorbitol excretion was normal. It is concluded that the impaired carbohydrate metabolism seen in MD is due to peripheral insulin resistance affecting various organs including the liver and it is suggested that the excessive beta-cell response is secondayr to the peripheral resistance.

Adult

Effects of endotoxin on carbohydrate metabolism in inbred mice.

Effects of endotoxin on carbohydrate metabolism were studied in A/HeJ (endotoxin-sensitive) and C3H/HeJ (endotoxin-resistant) inbred mice. A/HeJ mice developed hypoglycemia within two hours after endotoxin injection, yet liver glycogen content did not differ from controls. Similarly treated C3H/HeJ mice did not develop significant hypoglycemia. Administration of glucagon to endotoxin-treated A/HeJ mice failed to elevate their blood glucose concentrations, while endotoxin-treated mice of the same strain did respond to dibutyryl cyclic AMP with a significant elevation of blood glucose. C3H/HeJ mice on the other hand responded to glucagon and dibutyryl cyclic AMP with elevated blood glucose. Endotoxin-treated C3H/HeJ but not A/HeJ mice were able to carry out gluconeogenesis induced by prednisolone, while both inbred strains showed active glycogenesis after administration of an exogenous glucose load. Administration of glucagon resulted in diminished liver glycogen concentrations in A/HeJ endotoxin-treated mice suggesting no impairment of glycogenolysis. The inability of endotoxin-treated A/HeJ mice to respond to glucagon could be due to impairment of gluconeogenesis. Although endotoxin interfered with the capacity of both inbred strains to respond to glucagon administration with elevation of liver cyclic AMP, the effect was significantly more severe in A/HeJ mice. The susceptibility of A/HeJ mice to the lethal effect of endotoxin may be related to the apparent sensitivity of carbohydrate metabolic pathways to disturbance by endotoxin.

Animals

Hormonal interactions in carbohydrate metabolism.

Insulin is the key hormone of carbohydrate metabolism, it also influences the metabolism of fat and proteins. It lowers blood glucose by increasing glucose transport in muscle and adipose tissue and stimulates the synthesis of glycogen, fat, and protein. The anabolic action of insulin is antagonized by the catabolic action of glucagon. This hormone stimulates glycogenolysis and gluconeogenesis. The molar insulin: glucagon ratio is a parameter for an anabolic or a catabolic situation. Epinephrine also antagonizes insulin action. Like glucagon it stimulates glycogenolysis. In addition it reduces the insulin sensitivity of peripheral tissues and inhibits the release of insulin. Growth hormone decreases glucose uptake in muscle and adipose tissue gluconeogenesis in liver. In the presence of insulin, growth hormone stimulates protein synthesis. The net metabolic effects of a single hormone are directly related to the activity of other synergistic or antagonistic hormones.

Adipose Tissue