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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alcoholic ketoacidosis is an acute metabolic acidosis that typically occurs in people who chronically abuse alcohol and have a recent history of binge drinking, little or no food intake and persistent vomiting. Alcoholic ketoacidosis is a result of starvation with glycogen depletion and counter-regulatory hormone production, a raised nicotinamide adenine dinucleotide (NADH) to nicotinamide adenine dinucleotide (NAD+) ratio related to the metabolism of ethanol, and volume depletion resulting in ketogenesis. Alcoholic ketoacidosis is characterized by elevated serum ketone levels and a high anion gap. Once the diagnosis of alcoholic ketoacidosis is made, the mainstay of treatment is hydration with 5% dextrose in normal saline. With timely and aggressive intervention, the prognosis for a patient with alcoholic ketoacidosis is good.
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PMID:[Alcoholic ketoacidosis]. 1929 98

The molecular mechanism involved in tolerance and adaptation of ethanologenic Saccharomyces cerevisiae to inhibitors (such as furfural, acetic acid, and phenol) represented in lignocellulosic hydrolysate is still unclear. Here, (18)O-labeling-aided shotgun comparative proteome analysis was applied to study the global protein expression profiles of S. cerevisiae under conditions of treatment of furfural compared with furfural-free fermentation profiles. Proteins involved in glucose fermentation and/or the tricarboxylic acid cycle were upregulated in cells treated with furfural compared with the control cells, while proteins involved in glycerol biosynthesis were downregulated. Differential levels of expression of alcohol dehydrogenases were observed. On the other hand, the levels of NADH, NAD(+), and NADH/NAD(+) were reduced whereas the levels of ATP and ADP were increased. These observations indicate that central carbon metabolism, levels of alcohol dehydrogenases, and the redox balance may be related to tolerance of ethanologenic yeast for and adaptation to furfural. Furthermore, proteins involved in stress response, including the unfolded protein response, oxidative stress, osmotic and salt stress, DNA damage and nutrient starvation, were differentially expressed, a finding that was validated by quantitative real-time reverse transcription-PCR to further confirm that the general stress responses are essential for cellular defense against furfural. These insights into the response of yeast to the presence of furfural will benefit the design and development of inhibitor-tolerant ethanologenic yeast by metabolic engineering or synthetic biology.
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PMID:Comparative proteomic analysis of tolerance and adaptation of ethanologenic Saccharomyces cerevisiae to furfural, a lignocellulosic inhibitory compound. 1936 68

Ketone bodies serve as alternative energy substrates for the brain in cases of low glucose availability such as during starvation or in patients treated with a ketogenic diet. The ketone bodies are metabolized via a distinct pathway confined to the mitochondria. We have compared metabolism of [2,4-(13)C]beta-hydroxybutyrate to that of [1,6-(13)C]glucose in cultured glutamatergic neurons and investigated the effect of neuronal activity focusing on the aspartate-glutamate homeostasis, an essential component of the excitatory activity in the brain. The amount of (13)C incorporation and cellular content was lower for glutamate and higher for aspartate in the presence of [2,4-(13)C]beta-hydroxybutyrate as opposed to [1,6-(13)C]glucose. Our results suggest that the change in aspartate-glutamate homeostasis is due to a decreased availability of NADH for cytosolic malate dehydrogenase and thus reduced malate-aspartate shuttle activity in neurons using beta-hydroxybutyrate. In the presence of glucose, the glutamate content decreased significantly upon activation of neurotransmitter release, whereas in the presence of only beta-hydroxybutyrate, no decrease in the glutamate content was observed. Thus, the fraction of the glutamate pool available for transmitter release was diminished when metabolizing beta-hydroxybutyrate, which is in line with the hypothesis of formation of transmitter glutamate via an obligatory involvement of the malate-aspartate shuttle.
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PMID:Availability of neurotransmitter glutamate is diminished when beta-hydroxybutyrate replaces glucose in cultured neurons. 1945 63

Although the tricarboxylic acid (TCA) cycle is essential in almost all aerobic organisms, its precise modulation and integration in global cellular metabolism is not fully understood. Here, we report on an alternative TCA cycle uniquely aimed at generating ATP and oxalate, two metabolites critical for the survival of Pseudomonas fluorescens. The upregulation of isocitrate lyase (ICL) and acylating glyoxylate dehydrogenase (AGODH) led to the enhanced synthesis of oxalate, a dicarboxylic acid involved in the immobilization of aluminum (Al). The increased activity of succinyl-CoA synthetase (SCS) and oxalate CoA-transferase (OCT) in the Al-stressed cells afforded an effective route to ATP synthesis from oxalyl-CoA via substrate level phosphorylation. This modified TCA cycle with diminished efficacy in NADH production and decreased CO(2)-evolving capacity, orchestrates the synthesis of oxalate, NADPH, and ATP, ingredients pivotal to the survival of P. fluorescens in an Al environment. The channeling of succinyl-CoA towards ATP formation may be an important function of the TCA cycle during anaerobiosis, Fe starvation and O(2)-limited conditions.
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PMID:An ATP and oxalate generating variant tricarboxylic acid cycle counters aluminum toxicity in Pseudomonas fluorescens. 1980 98

Mono-ADP-ribosylation is the enzymatic transfer of ADP-ribose from NAD(+) to acceptor proteins catalyzed by ADP-ribosyltransferases. Using m-aminophenylboronate affinity chromatography, 2D-gel electrophoresis, in-gel digestion and MALDI-TOF analysis we have identified eight in vitro ADP-ribosylated proteins in Streptomyces coelicolor, which can be classified into three categories: (i) secreted proteins; (ii) metabolic enzymes using NAD(+)/NADH or NADP(+)/NADPH as coenzymes; and (iii) other proteins. The secreted proteins could be classified into two functional categories: SCO2008 and SC05477 encode members of the family of periplasmic extracellular solute-binding proteins, and SCO6108 and SC01968 are secreted hydrolases. Dehydrogenases are encoded by SC04824 and SC04771. The other targets are GlnA (glutamine synthetase I., SC02198) and SpaA (starvation-sensing protein encoded by SC07629). SCO2008 protein and GlnA had been identified as ADP-ribosylated proteins in previous studies. With these results we provided experimental support for a previous suggestion that ADP-ribosylation may regulate membrane transport and localization of periplasmic proteins. Since ADP-ribosylation results in inactivation of the target protein, ADP-ribosylation of dehydrogenases might modulate crucial primary metabolic pathways in Streptomyces. Several of the proteins identified here could provide a strong connection between protein ADP-ribosylation and the regulation of morphological differentiation in S. coelicolor.
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PMID:Analysis and identification of ADP-ribosylated proteins of Streptomyces coelicolor M145. 1985 27

NADH is a naturally fluorescent metabolite associated with cellular respiration. Exploiting the different fluorescence lifetime of free and bound NADH has the potential to quantify the relative amount of bound and free NADH, enhancing understanding of cellular processes including apoptosis, cancer pathology, and enzyme kinetics. We use the phasor-fluorescence lifetime image microscopy approach to spatially map NADH in both the free and bound forms of live undifferentiated and differentiated myoblast cells. The phasor approach graphically depicts the change in lifetime at a pixel level without the requirement for fitting the decay. Comparison of the spatial distribution of NADH in the nucleus of cells induced to differentiate through serum starvation and undifferentiated cells show differing distributions of bound and free NADH. Undifferentiated cells displayed a short lifetime indicative of free NADH in the nucleus and a longer lifetime attributed to the presence of bound NADH outside of the nucleus. Differentiating cells displayed redistribution of free NADH with decreased relative concentration of free NADH within the nucleus whereas the majority of NADH was found in the cytoplasm.
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PMID:NADH distribution in live progenitor stem cells by phasor-fluorescence lifetime image microscopy. 2282 52

Analysis of the cellular distributions of coenzymes including NADH may aid in understanding a cells metabolic status. We altered serum concentration (0, 2, and 10%) to induce living myoblast cells to undergo the early stages of differentiation. Through microscopy and phasor-FLIM, we spatially mapped and identified variations in the distribution of free and bound NADH. Undifferentiated cells displayed abundant free NADH within the nucleus along with specific regions of more bound NADH. Complete serum starvation dramatically increased the fraction of bound NADH in the nucleus, indicating heightened requirement for transcriptional processes. In comparison, cells exposed to 2% serum exhibited intermediate free nuclear NADH fraction. Overall our results suggest an order of events in which a cell metabolic status alters significantly during the early stages of serum induced differentiation.
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PMID:Phasor-FLIM analysis of NADH distribution and localization in the nucleus of live progenitor myoblast cells. 2301 16

A commonly used enzymatic recycling assay for pyridine nucleotides has been adapted to directly measure the NAD(+)/NADH redox ratio in Drosophila melanogaster. This method is also suitable for quantification of NADP(+) and NADPH. The addition of a coupling reaction removing acetaldehyde produced from the alcohol dehydrogenase (ADH) reaction was shown to improve the linearity of NAD(H) assay. The advantages of this assay method are that it allows the determination of both NAD(+) and NADH simultaneously while keeping enzymatic degradation of pyridine nucleotides minimal and also achieving better sensitivity. This method was used to determine the redox ratio of D. melanogaster and validated substantial decrease of redox ratio during starvation.
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PMID:A hydrazine coupled cycling assay validates the decrease in redox ratio under starvation in Drosophila. 2308 79

Cells undergoing malignant transformation often exhibit a shift in cellular metabolism from oxidative phosphorylation to glycolysis. This glycolytic shift, called the Warburg effect, provides a mechanistic basis for targeting glycolysis to suppress carcinogenesis through the use of dietary caloric restriction and energy restriction-mimetic agents (ERMA). We recently reported the development of a novel class of ERMAs that exhibits high potency in eliciting starvation-associated cellular responses and epigenetic changes in cancer cells though glucose uptake inhibition. The lead ERMA in this class, OSU-CG5, decreases the production of ATP and NADH in LNCaP prostate cancer cells. In this study, we examined the effect of OSU-CG5 on the severity of preneoplastic lesions in male transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. Daily oral treatment with OSU-CG5 at 100 mg/kg from 6 to 10 weeks of age resulted in a statistically significant decrease in the weight of urogenital tract and microdissected dorsal, lateral, and anterior prostatic lobes relative to vehicle controls. The suppressive effect of OSU-CG5 was evidenced by marked decreases in Ki67 immunostaining and proliferating cell nuclear antigen (PCNA) expression in the prostate. OSU-CG5 treatment was not associated with evidence of systemic toxicity. Microarray analysis indicated a central role for Akt, and Western blot analysis showed reduced phosphorylation and/or expression levels of Akt, Src, androgen receptor, and insulin-like growth factor-1 receptor in prostate lobes. These findings support further investigation of OSU-CG5 as a potential chemopreventive agent.
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PMID:Suppression of prostate epithelial proliferation and intraprostatic progrowth signaling in transgenic mice by a new energy restriction-mimetic agent. 2327 6

In mammals, there are different metabolic pathways in cells that break down fuel molecules to transfer their energy into high energy compounds such as adenosine-5'-triphosphate (ATP), guanosine-5'-triphosphate (GTP), reduced nicotinamide adenine dinucleotide (NADH2), reduced flavin adenine dinucleotide (FADH2) and reduced nicotinamide adenine dinucleotide phosphate (NADPH2). This process is called cellular respiration. In carbohydrate metabolism, the breakdown starts from digestion of food in the gastrointestinal tract and is followed by absorption of carbohydrate components by the enterocytes in the form of monosaccharides. Monosaccharides are transferred to cells for aerobic and anaerobic respiration via glycolysis, citric acid cycle and pentose phosphate pathway to be used in the starvation state. In the normal state, the skeletal muscle and liver cells store monosaccharides in the form of glycogen. In the obesity state, the extra glucose is converted to triglycerides via lipogenesis and is stored in the lipid droplets of adipocytes. In the lipotoxicity state, the lipid droplets of other tissues such as the liver, skeletal muscle and pancreatic beta cells also accumulate triacylglycerol. This event is the axis of the pathogenesis of metabolic dysregulation in insulin resistance, metabolic syndrome and type 2 diabetes. In this paper a summary of the metabolism of carbohydrates is presented in a way that researchers can follow the biochemical processes easily.
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PMID:A quick look at biochemistry: carbohydrate metabolism. 2368 95


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