Starvation causes disturbance in amino acid and fatty acid metabolism in Diporeia

Cardiomyocytes rely on specialised metabolism to meet the high energy demand of the heart. During heart development, metabolism matures and shifts from the predominant utilisation of glycolysis and glutamine oxidation towards lactate and fatty acid oxidation. Iron deficiency (ID) leads to cellular metabolism perturbations. However, the exact alterations in substrate metabolism during ID are poorly defined. Using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM), the present study investigated changes in major metabolic substrate utilisation in the context of ID or upon transferrin rescue. Typically, during hiPSC-CM differentiation, the greatest increase in total metabolic output and rate was seen in fatty acid metabolism. When ID was induced, hiPSC-CMs displayed increased reliance on glycolytic metabolism, and six TCA cycle, five amino acid, and four fatty acid substrates were significantly impaired. Transferrin rescue was able to improve TCA cycle substrate metabolism, but the amino acid and fatty acid metabolism remained perturbed. Replenishing iron stores partially reverses the adverse metabolic changes that occur during ID. Understanding the changes in metabolic substrate utilisation and their modification may provide potential for discovery of new biomarkers and therapeutic targets in cardiovascular diseases.

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Plasma Metabolic Profiling Analysis of Gout Party on Acute Gout Arthritis Rats Based on UHPLC–Q–TOF/MS Combined with Multivariate Statistical Analysis

International Journal of Molecular Sciences ◽

10.3390/ijms20225753 ◽

2019 ◽

Vol 20 (22) ◽

pp. 5753 ◽

Cited By ~ 2

Author(s):

Yuming Wang ◽

Chenghao Bi ◽

Wentao Pang ◽

Yuechen Liu ◽

Yu Yuan ◽

...

Keyword(s):

Fatty Acid ◽

Amino Acid ◽

Energy Metabolism ◽

Fatty Acid Metabolism ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Gouty Arthritis ◽

Enoic Acid ◽

Plasma Samples ◽

Tof Ms

Gout Party is a Chinese medicine prescription composed of Aconiti Lateralis Radix Praeparaia, Aconiti Radix Cocta, Cremastrae Pseudobulbus Pleiones Pseudobulbus, Smilacis Glabrae Rhizoma, Rehmanniae Radix, and Glycyrrhizae Radix et Rhizoma, which can relieve joint pain caused by gouty arthritis (GA) and rheumatoid, and has a therapeutic effect on acute gouty arthritis (AGA). However, little information is available on the molecular biological basis and therapeutic mechanism of Gout Party for the treatment of AGA. AGA model was established by injecting sodium urate, and colchicine served as a positive control drug. We established a metabolomic method based on ultra-high-performance liquid chromatography–tandem quadrupole/time-of-flight mass spectrometry (UHPLC–Q–TOF/MS) to analyze the plasma samples of model group rats and blank group rats. Multiple statistical analyses, including principal component analysis (PCA) and partial least square discrimination analysis (PLS-DA), were used to examine metabolite profile changes in plasma samples. Finally, we identified 2–ketobutyric acid, 3–hexenedioic acid, but–2–enoic acid, and so on; 22 endogenous metabolites associated with AGA. After successful molding, we found that 2–ketobutyric acid, 3–hexenedioic acid, but–2–enoic acid, argininic acid, galactonic acid, lactic acid, equol 4′–O–glucuronide, deoxycholic acid glycine conjugate, glycocholic acid, sphinganine 1–phosphate, LPE (0:0/20:3), LPE (0:0/16:0), LPC (15:0) decreased significantly (p < 0.05 or p < 0.01), alanine, erythrulose, 3–dehydrocarnitine, m–methylhippuric acid, 3–hydroxyoctanoic acid, p–cresol sulfate, estriol 3–sulfate 16–glucuronide, 10–hydroxy–9–(phosphonooxy)octadecenoate, docosahexaenoic acid increased significantly (p < 0.05 or p < 0.01). After Gout Party treatment, 14 biomarkers had a tendency to normal conditions. These above biomarkers were mainly involved in fatty acid metabolism, bile acid metabolism, amino acid metabolism, and energy metabolism pathways. These results suggested that Gout Party exerted therapeutic effects of treating AGA by improving energy metabolism disorder and amino acid metabolism dysfunction, and attenuating fatty acid metabolism abnormal and inflammation. The results of this experiment provided a reference for revealing the metabolic mechanism produced by Gout Party in the treatment of AGA, but the subsequent studies need to be further improved and supported by relevant cell experiments and clinical experiments.

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Hepatic cytochrome P-450 reductase-null mice show reduced transcriptional response to quercetin and reveal physiological homeostasis between jejunum and liver

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00565.2005 ◽

2006 ◽

Vol 291 (1) ◽

pp. G63-G72 ◽

Cited By ~ 10

Author(s):

David M. Mutch ◽

Vanessa Crespy ◽

Jennifer Clough ◽

Colin J. Henderson ◽

Sofiane Lariani ◽

...

Keyword(s):

Small Intestine ◽

Fatty Acid ◽

Amino Acid ◽

Fatty Acid Metabolism ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Glutathione Metabolism ◽

Sterol Metabolism ◽

Cytochrome P 450 ◽

Hepatic Cytochrome

Using mice deficient in hepatic cytochrome P-450 oxidoreductase (POR), which disables the liver cytochrome P-450 system, we examined the metabolism and biological response of the anticarcinogenic flavonoid, quercetin. Profiling circulating metabolites revealed similar profiles over 72 h in wild-type (WT) and POR-null (KO) mice, showing that hepatic P450 and reduced biliary secretion do not affect quercetin metabolism. Transcriptional profiling at 24 h revealed that two- to threefold more genes responded significantly to quercetin in WT compared with KO in the jejunum, ileum, colon, and liver, suggesting that hepatic P450s mediate many of the biological effects of quercetin, such as immune function, estrogen receptor signaling, and lipid, glutathione, purine, and amino acid metabolism, even though quercetin metabolism is not modified. The functional interpretation of expression data in response to quercetin (single dose of 7 mg/animal) revealed a molecular relationship between the liver and jejunum. In WT animals, amino acid and sterol metabolism was predominantly modulated in the liver, fatty acid metabolism response was shared between the liver and jejunum, and glutathione metabolism was modulated in the small intestine. In contrast, KO animals do not regulate amino acid metabolism in the liver or small intestine, they share the control of fatty acid metabolism between the liver and jejunum, and regulation of sterol metabolism is shifted from the liver to the jejunum and that of glutathione metabolism from the jejunum to the liver. This demonstrates that the quercetin-mediated regulation of these biological functions in extrahepatic tissues is dependent on the functionality of the liver POR. In conclusion, using a systems biology approach to explore the contribution of hepatic phase 1 detoxification on quercetin metabolism demonstrated the resiliency and adaptive capacity of a biological organism in dealing with a bioactive nutrient when faced with a tissue-specific molecular dysfunction.

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Mapping amino acid and short-chain fatty acid metabolism in man

10.26481/dis.20191023en ◽

2019 ◽

Author(s):

Neis

Keyword(s):

Fatty Acid ◽

Amino Acid ◽

Fatty Acid Metabolism ◽

Short Chain Fatty Acid ◽

Acid Metabolism ◽

Chain Fatty Acid ◽

Short Chain

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Metabolic Disorders: Inborn Errors of Amino Acid, Ammonia, Organic Acid, and Fatty Acid Metabolism

10.2310/im.1310 ◽

2015 ◽

Author(s):

Sameer S Chopra ◽

Gerard T Berry

Keyword(s):

Fatty Acid ◽

Amino Acid ◽

Organic Acid ◽

Small Molecule ◽

Fatty Acid Metabolism ◽

Metabolic Disorders ◽

Acid Metabolism ◽

Genetic Disorders ◽

Inborn Errors ◽

Branched Chain

The small molecule diseases include inborn errors of carbohydrate, ammonia, amino acid, organic acid, and fatty acid metabolism. They are central among the biochemical genetic disorders that may present with life-threatening illnesses during infancy and childhood. Many of these disorders are now detected through routine newborn screening. Internists should be familiar with small molecule metabolic disorders as early diagnosis and therapy may enable many patients to survive into adulthood. Additionally, because some patients may not manifest symptoms until late adolescence or adulthood, recognition of the possibility of an inborn error of metabolism in a patient with unusual signs or symptoms may lead to referral to a metabolic specialist and timely diagnosis and treatment. This module reviews the diagnosis, treatment, and natural history of disorders of amino acid, ammonia, organic acid, and fatty acid metabolism. Figures show the methionine-homocysteine-cysteine pathway and branched-chain amino acid metabolism. This module contains 2 highly rendered figures, 18 references, 53 recommended readings, and 5 MCQs.

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