Inhibition Of Carbohydrate Metabolism Research Articles

Recent advances in plant‐based compounds for mitigation of mycotoxin contamination in food products: current status, challenges and perspectives

SummaryThere are numerous strategies to control the growth of mycotoxigenic fungi and reduce mycotoxins in food, including physical, chemical and biological treatments. However, consumers prefer organic food and natural inhibitors because they are biodegradable and safe for human and animal health. This review summarises the current advances in plant‐based compounds to mitigate contamination of food products by mycotoxigenic fungi and their toxins. In addition, a clear understanding of the roles of plant‐based extracts in food products, their mechanisms of action and challenges and perspectives in mycotoxin degradation are presented. Essential oils and plant‐based extracts are complex mixtures of major and minor chemical compounds with antimicrobial and antioxidant properties. In general, the mechanisms of antifungal activity of plant‐based compounds are attributed to the reduction of the ergosterol content, disruption of cell membrane integrity, enhancing of membrane ion leakage and permeability, disruption to the organisation of mitochondrial structure, interference in enzymatic reactions of cell wall synthesis, disturbance of oxidative balance, inhibition of carbohydrate metabolism, suppression of mycotoxin biosynthetic genes and alterations in the molecular structure of mycotoxins.

Inhibition of carbohydrate metabolism by thermal fluctuations during endodormancy lead to negative impacts on bud burst and incidence of floral necrosis in ‘Housui’ Japanese pear flower buds

Challenges related to bud dormancy release are important limiting factors to commercial fruit production of Japanese pear (Pyrus pyrifolia Nakai) in areas under mild winter conditions. This study aimed to elucidate the effects of thermal fluctuations that occur in areas with mild winters on endodormancy release of Japanese pear flower buds. ‘Housui’ Japanese pear trees exposed to thermal fluctuations were left to accumulate 600 chilling hours (CH) in order to simulate mild winter conditions and subsequently moved into a greenhouse to observe bud burst and number of flowers/cluster. During endodormancy progression, the concentration of sugars, starch and α-amylase activity were analyzed in lateral flower buds and stems collected at 0, 300 and 600 CH. In addition, necrosis of floral primordia was examined in buds collected over the same period. Thermal fluctuations during endodormancy caused floral primordia necrosis at 300 CH and 600 CH and tended to decrease bud burst percentages. Low concentrations of soluble sugars were observed in buds and stems subjected to thermal fluctuations during endodormancy. Lower percentage of bud burst and incidence of floral primordia necrosis may be a result of low sucrose observed in buds. Hexoses and sorbitol that are important for energy and carbon supply as well freeze tolerance during endodormancy were lower in buds and stem exposed to thermal fluctuations. Thermal fluctuations inhibited the activity of α-amylase in buds and retarded the degradation of starch, leading to low accumulation of soluble sugars during endodormancy. These results suggest that carbohydrate metabolism is inhibited by thermal fluctuations during endodormancy under mild winter conditions, and that low availability of sufficient carbohydrate during winter may lead to floral primordia necrosis and abnormal patterns of endodormancy release in Japanese pear.

HO-1/EBP interaction alleviates cholesterol-induced hypoxia through the activation of the AKT and Nrf2/mTOR pathways and inhibition of carbohydrate metabolism in cardiomyocytes.

Heme oxygenase-1 (HO-1) is an inducible and cytoprotective enzyme that provides a defense against oxidant damage. The present study screened 137 HO-1/interacting proteins using a profound co-immunoprecipitation (Co-IP) coupled with proteomics, and profiled the global HO-1 interactome network, including oxidative phosphorylation, endoplasmic reticulum and transport vesicle functions. Among these molecules, we observed that a novel interactor, emopamil-binding protein (EBP), is closely related to the cholesterol metabolism process. This study demonstrated that cholesterol promotes excessive oxidative stress and alters the energy metabolism in cardiomyocytes, further triggering numerous cardiovascular diseases. We observed that cholesterol caused the overexpression of EBP and HO-1 by the activation of AKT and Nrf2/mTOR pathways. In addition, HO-1 and EBP performed a myocardial protective function. The overexpression of HO-1 alleviated the cholesterol-induced excessive oxidative stress status by inhibition of the carbohydrate metabolism. Notably, we also confirmed that the loss of partial HO-1 activity aggravated the oxidative damage and cardiac systolic function induced by a high-fat diet in HO-1 heterozygous (HO-1+/−) mice. These findings indicate that the HO-1/EBP interaction plays a protective role in alleviating the dysfunction of oxidative stress and cardiac systolic function induced by cholesterol stimulation.

A Phaseolus vulgaris Extract Reduces Cue-Induced Reinstatement of Chocolate Seeking in Rats

Previous evidence has suggested that treatment with a standardized dry extract of Phaseolus vulgaris reduced intake and operant self-administration of highly palatable foods and fluids in rats and mice. The present study was designed to assess whether such extract was also effective in reducing seeking behavior for a highly hedonic chocolate-flavored beverage, using a “reinstatement” procedure adopted from the drug addiction research field and modeling relapse behavior. Rats were initially trained to lever-respond for the chocolate-flavored beverage under the Fixed Ratio (FR) 10 schedule of reinforcement. Subsequently, rats were exposed to an extinction responding phase, during which lever-responding – being unreinforced – diminished progressively up to extinction. Lever-responding was then powerfully reinstated by the non-contingent presentation of a complex of gustatory, olfactory, auditory, and visual stimuli previously associated to the availability of the chocolate-flavored beverage. Acute, intragastric administration of P. vulgaris dry extract (100 and 500 mg/kg) reduced lever-responding by 40–45%, in comparison to vehicle condition. These results indicate the ability of P. vulgaris dry extract to reduce seeking behavior for a highly palatable nourishment in an experimental model of relapse into disordered eating of palatable foods. The unavailability of the chocolate-flavored beverage in the reinstatement session tends to exclude that the observed effect of the P. vulgaris dry extract was secondary to any inhibition of carbohydrate metabolism; conversely, it is the likely consequence on a central action on the rewarding and hedonic properties of food.

Investigation of an Amylase Inhibitor on Human Glucose Absorption after Starch Consumption

Inhibition of carbohydrate metabolism or absorption can decrease calorie intake to promote weight loss and combat obesity. It is also a mechanism for reducing hyperglycemia in diabetic subjects. A concentrated northern kidney bean extract was found to be an effective in vitro amylase inhibitor, thus potentially affecting the absorption of starch carbohydrates. This product was tested in two single dose human studies. Eleven fasting subjects were given 4 slices of white bread and 42 g of margarine with or without 1.5 g of bean extract. Absorption as measured by the area under the plasma glucose-time curve was inhibited 66%. A full meal study with 7 subjects and 0.75 g of extract caused a non-significant 28-41% reduction in absorption. There was a dose-response decrease in glucose absorption by the extract. The bean extract has in vivo efficacy for inhibition of starch absorption and may prove beneficial in weight reduction in individuals consuming large amounts of starch. It also may inhibit starch-induced hyperglycemia in normal and diabetic subjects.

Design and Screening Strategies for α-Glucosidase Inhibitors Based on Enzymological Information

Alpha-glucosidase inhibitors are marketed as therapeutic drugs for diabetes that act through the inhibition of carbohydrate metabolism. Inhibitors of the alpha-glucosidases that are involved in the biosynthesis of N-linked oligosaccharide chains have been reported to have antitumor, antiviral, and apoptosis-inducing activities, and some have been used clinically. alpha-Glucosidase inhibitors have interesting biological activities, and their design, synthesis, and screening are being actively performed. In quite a few reports, however, alpha-glucosidases with different origins than the target alpha-glucosidases, have been used to evaluate inhibitory activities. There might be confusion regarding the naming of alpha-glucosidases. For example, the term alpha-glucosidase is sometimes used as a generic name for alpha-glucoside hydrolases. Moreover, IUBMB recommends the use of "alpha-glucosidase" (EC 3.2.1.20) for exo-alpha-1,4-glucosidases, which are further classified into four families based on amino acid sequence similarities. Accordingly, substrate specificity and susceptibility to inhibitors varies markedly among enzymes in the IUBMB alpha-glucosidases. The design and screening of inhibitors without consideration of these differences is not efficient. For the development of a practical inhibitor that is operational in cells, HTS using the target alpha-glucosidase and the computer-aided design of inhibitors based on enzymatic information concerning the same alpha-glucosidase are essential.

Regulation of fat metabolism in skeletal muscle.

Regulation of carbohydrate and fat utilization by skeletal muscle at rest and during exercise has been the subject of investigation since the early 1960s when Randle et al. proposed the so-called glucose-fatty acid cycle to explain the reciprocal relationship between carbohydrate and fat metabolism. The suggested mechanisms were based on the premise that an increase in fatty acid (FA) availability would result in increased fat metabolism and inhibition of carbohydrate metabolism. Briefly, accumulation of acetyl-CoA would result in inhibition of pyruvate dehydrogenase (PDH), accumulation of citrate would inhibit phosphofructokinase (PFK), and accumulation of glucose-6-phosphate (G6P) would reduce hexokinase (HK) activity. Ultimately, this would inhibit carbohydrate metabolism with increasing availability and oxidation of FA. Although there is some evidence for the existence of the glucose-FA cycle at rest and during low-intensity exercise, it cannot explain substrate use at moderate to high exercise intensities. More recently, evidence has accumulated that increases in glycolytic flux may decrease fat metabolism. Potential sites of regulation are the transport of FA into the sarcoplasma, lipolysis of intramuscular triacylglycerol (IMTG) by hormone-sensitive lipase (HSL), and transport of FA across the mitochondrial membrane. There are several potential regulators of fat oxidation: first, malonyl-CoA concentration, which is formed from acetyl-CoA, catalyzed by the enzyme acetyl-CoA carboxylase (ACC), which in turn will inhibit carnitine palmitoyl transferase I (CPT I). Another possible mechanism is accumulation of acetyl-CoA that will result in acetylation of the carnitine pool, reducing the free carnitine concentration. This could theoretically reduce FA transport into the mitochondria. There is also some recent evidence that CPT I is inhibited by small reductions in pH that might be observed during exercise at high intensities. It is also possible that FA entry into the sarcolemma is regulated by translocation of FAT/CD36 in a similar manner to glucose transport by GLUT-4. Studies suggest that the regulatory mechanisms may be different at rest and during exercise and may change as the exercise intensity increases. Regulation of skeletal muscle fat metabolism is clearly multifactorial, and different mechanisms may dominate in different conditions.

Fatty acid oxidation modulates the eating response to the fructose analogue 2,5-anhydro-D-mannitol.

The fructose analogue 2,5-anhydro-D-mannitol (2,5-AM) stimulates feeding behavior in rats apparently through its effects on hepatic energy metabolism, where it reduces glucose utilization, traps phosphate, and decreases ATP. The extent to which the magnitude and duration of the eating response are dependent on the ability of the liver to switch to fat oxidation for energy production was investigated by manipulating substrate availability through dietary and pharmacological means. Rats adapted to a high-fat, low-carbohydrate diet preferentially use fat fuels for hepatic energy production and were insensitive to the effects of 2,5-AM on food intake. The lack of an eating response occurred despite similar changes in plasma fuels and liver glycogen compared with rats fed a low-fat, high-carbohydrate diet. In contrast, inhibiting fatty acid oxidation with methyl palmoxirate, which blocks transport of long-chain fatty acids to the mitochondria, potentiated the ability of 2,5-AM to stimulate feeding without altering its effects on plasma and liver fuels. These data demonstrate that the eating response to 2,5-AM is modulated by the availability of fat fuels and implicate a mechanism for initiation of feeding that is not dependent on inhibition of carbohydrate metabolism per se but rather integrates information about the use of both types of fuels.

Studies on the biochemical basis of oxygen toxicity

The toxic effects of high pressure oxygen on the isolated toad urinary bladder have been studied. Sodium transport in this system is reversibly inhibited by high pressure O 2. This inhibition is potentiated by adrenal steroid hormones, and occurs despite both increased glycolytic and Kreb's cycle flux and tissue ATP content. High pressure O 2 leads to increased pyruvate/lactate and pyruvate/malate redox couples, as well as to a decrease in the weight percentage of phospholipid long-chain unsaturated fatty acids and [2- 14C]pyruvate incorporation into tissue lipid. During recovery from high pressure O 2 treatment, [2- 14C]Pyruvate incorporation into lipid is increased and the weight percentage of long-chain unsaturated fatty acids increases. These data indicate that high pressure O 2 poisoning in this tissue does not result from an inhibition of carbohydrate metabolism, but may result from the formation of toxic lipid peroxides.

Inhibition of Carbohydrate Metabolism by Oxygen and N-Ethylmaleimide in Rat Heart Homogenates

The inhibitory effects of oxygen and N-ethylmaleimide upon glycolysis and adenosine triphosphate accumulation in rat heart homogenate systems were studied. The main effect of N-ethylmaleimide was to inhibit ATP synthesis and thus to decrease the phosphorylation of glucose and fructose 6-phosphate. It is likely that this compound exerts its action by interfering with reactions of the tricarboxylic acid cycle or electron transport. Oxygen at a pressure of 1 atm was found to inhibit glycolysis directly. The experiments provide strong evidence that the mechanism of this inhibitory effect of oxygen involves the inactivation of glyceraldehyde 3-phosphate dehydrogenase by oxidation of enzyme sulfhydryl groups. Depression of glycolysis by oxygen was prevented by reduced glutathione, cysteine, and dithiothreitol. Some protection against oxygen toxicity was afforded by ascorbic acid. Addition of dithiothreitol or reduced glutathione to a homogenate system inhibited by oxygen caused a reversal of the toxic effects of oxygen.

The inhibition of carbohydrate metabolism in ascites-tumour cells by ethyleneimines

The inhibition of carbohydrate metabolism in ascites-tumour cells by ethyleneimines

Mode of action of streptomycin in relation to thechanges in spinal fluid sugar in tuberculous meningitis: III. A theory of the mode of action of streptomycin in vivowith a commentary on the current literature

Summary A theory on the mode of action ofstreptomycin in tuberculous meningitis is presented that explains the rise of C.S.F. sugar after treatment with streptomycin. The hypothesis is formulated to correlate known clinical observations and laboratory data: Streptomycin in the injured cell in tuberculous meningitis causes inhibition of carbohydrate metabolism. The increase in spinal fluid sugar noted after the initial treatment with streptomycin is secondary to decreased utilization of glucose by the living cell and unimpaired flow of spinal fluid.

Action of mustard gas and other poisons on yeast cells. VI. Study of the relationship between inhibition of carbohydrate metabolism and inhibition of growth by various poisons, and effects of other toxic agents on yeast

Journal of Cellular and Comparative PhysiologyVolume 30, Issue 1 p. 31-42 Article Action of mustard gas and other poisons on yeast cells. VI. Study of the relationship between inhibition of carbohydrate metabolism and inhibition of growth by various poisons, and effects of other toxic agents on yeast† V. Everett Kinsey, V. Everett Kinsey Howe Laboratory of Ophthalmology, Harvard Medical School, Boston, MassachusettsSearch for more papers by this authorW. Morton Grant, W. Morton Grant Howe Laboratory of Ophthalmology, Harvard Medical School, Boston, MassachusettsSearch for more papers by this author V. Everett Kinsey, V. Everett Kinsey Howe Laboratory of Ophthalmology, Harvard Medical School, Boston, MassachusettsSearch for more papers by this authorW. Morton Grant, W. Morton Grant Howe Laboratory of Ophthalmology, Harvard Medical School, Boston, MassachusettsSearch for more papers by this author First published: August 1947 https://doi.org/10.1002/jcp.1030300104Citations: 11 † The work described in this paper was done under a contract, recommended by the Committee on Medical Research, between the Office of Scientific Research and Development and Harvard University. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume30, Issue1August 1947Pages 31-42 RelatedInformation