Branched Chain Amino Acids

Annual Review of Physiology, Journal Year: 2018, Volume and Issue: 81(1), P. 139 - 164

Published: Nov. 28, 2018

Branched chain amino acids (BCAAs) are building blocks for all life-forms. We review here the fundamentals of BCAA metabolism in mammalian physiology. Decades studies have elicited a deep understanding biochemical reactions involved catabolism. In addition, BCAAs and various catabolic products act as signaling molecules, activating programs ranging from protein synthesis to insulin secretion. How these processes integrated at an organismal level is less clear. Inborn errors highlight importance regulation More recently, subtle alterations been suggested contribute numerous prevalent diseases, including diabetes, cancer, heart failure. Understanding mechanisms underlying altered how they disease pathophysiology will keep researchers busy foreseeable future.

Language: Английский

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Biomarkers in Stress Related Diseases/Disorders: Diagnostic, Prognostic, and Therapeutic Values

Frontiers in Molecular Biosciences, Journal Year: 2019, Volume and Issue: 6

Published: Oct. 18, 2019

Various internal and external factors negatively affect the homeostatic equilibrium of organisms at molecular to whole-body level, inducing so-called state 'stress'. Stress affects an organism's welfare status induces energy-consuming mechanisms combat subsequent ill effects; thus, individual may be immunocompromised, making them vulnerable pathogens. The information presented here has been extensively reviewed, compiled analyzed from authenticated published resources available on Medline, Pubmed, Pubmed Central, Science Direct, other scientific databases. levels can monitored by quantitative qualitative measurement biomarkers. Prominent markers stress include thermal like heat shock proteins (HSPs), innate immune Acute Phase Proteins (APPs), oxidative markers, chemical secretions in saliva urine. In addition, biomarkers are thought play critical roles prognosis stress-related diseases disorders, therapy guidance. Moreover, different components have identified as potent mediators cardiovascular, central nervous system, hepatic, nephrological which also employed evaluate these conditions precisely, but with stringent validation specificity. Considerable advances made detection, quantitation, application present review describes current progress identifying biomarkers, their prognostic therapeutic values.

Language: Английский

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Multilevel omics for the discovery of biomarkers and therapeutic targets for stroke

Nature Reviews Neurology, Journal Year: 2020, Volume and Issue: 16(5), P. 247 - 264

Published: April 22, 2020

Language: Английский

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After another decade: LC–MS/MS became routine in clinical diagnostics

Clinical Biochemistry, Journal Year: 2020, Volume and Issue: 82, P. 2 - 11

Published: March 15, 2020

Tandem mass spectrometry – especially in combination with liquid chromatography (LC–MS/MS) is applied a multitude of important diagnostic niches laboratory medicine. It unquestioned its routine use and often unreplaceable by alternative technologies. This overview illustrates the development past decade (2009–2019) intends to provide insight into current standing future directions field. The instrumentation matured significantly, applications are well understood, vitro diagnostics (IVD) industry shaping market providing assay kits, certified instruments, first automated LC–MS/MS instruments as an analytical core. In many settings application still burdensome locally lab developed test (LDT) designs relying on highly specialized staff. cover wide range analytes therapeutic drug monitoring, endocrinology including newborn screening, toxicology. tasks that remain be mastered are, for example, quantification proteins means transition from targeted untargeted omics approaches pattern recognition/pattern discrimination key technology establishment decisions.

Language: Английский

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Metabolomics in Diabetes and Diabetic Complications: Insights from Epidemiological Studies

Cells, Journal Year: 2021, Volume and Issue: 10(11), P. 2832 - 2832

Published: Oct. 21, 2021

The increasing prevalence of diabetes and its complications, such as cardiovascular kidney disease, remains a huge burden globally. Identification biomarkers for the screening, diagnosis, prognosis complications better understanding molecular pathways involved in development progression can facilitate individualized prevention treatment. With advancement analytical techniques, metabolomics identify quantify multiple simultaneously high-throughput manner. Providing information on underlying metabolic pathways, further mechanisms progression. application epidemiological studies have identified novel type 2 (T2D) branched-chain amino acids, metabolites phenylalanine, energy metabolism, lipid metabolism. Metabolomics also been applied to explore potential modulated by medications. Investigating using systems biology approach integrating with other omics data, genetics, transcriptomics, proteomics, clinical data present comprehensive network causal inference. In this regard, deepen understanding, help therapeutic targets, improve management T2D complications. current review focused metabolomic disease from studies, will provide brief overview investigations T2D.

Language: Английский

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Implications of Altered Ketone Metabolism and Therapeutic Ketosis in Heart Failure

Circulation, Journal Year: 2020, Volume and Issue: 141(22), P. 1800 - 1812

Published: June 1, 2020

Despite existing therapy, patients with heart failure (HF) experience substantial morbidity and mortality, highlighting the urgent need to identify novel pathophysiological mechanisms therapies, as well. Traditional models for pharmacological intervention have targeted neurohormonal axes hemodynamic disturbances in HF. However, several studies now highlighted potential ketone metabolic modulation a promising treatment paradigm. During progression of HF, failing reduces fatty acid glucose oxidation, associated increases metabolism. Recent indicate that enhanced myocardial use is adaptive limited data demonstrate beneficial effects exogenous therapy animal humans This review will summarize current evidence supporting salutary role ketones HF including (1) normal use, (2) alterations metabolism heart, (3) therapeutic ketosis animals (4) significance sodium-glucose cotransporter 2 inhibitors. Although number important questions remain regarding mechanism action suggests benefit, particular, reduced ejection fraction, theoretical rationale its preserved fraction. it early study development, across spectrum holds significant promise.

Language: Английский

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The Potential of Metabolomics in Biomedical Applications

Metabolites, Journal Year: 2022, Volume and Issue: 12(2), P. 194 - 194

Published: Feb. 19, 2022

The metabolome offers a dynamic, comprehensive, and precise picture of the phenotype. Current high-throughput technologies have allowed discovery relevant metabolites that characterize wide variety human phenotypes with respect to health, disease, drug monitoring, even aging. Metabolomics, parallel genomics, has led biomarkers aided in understanding diversity molecular mechanisms, highlighting its application precision medicine. This review focuses on metabolomics can be applied improve as well trends impacts metabolic neurodegenerative diseases, cancer, longevity, exposome, liquid biopsy development, pharmacometabolomics. identification distinct metabolomic profiles will help improvement clinical strategies treat disease. In years come, become tool routinely diagnose monitor health aging, or development. Biomedical applications already foreseen progression such obesity diabetes, using branched-chain amino acids, acylcarnitines, certain phospholipids, genomics; these assess disease severity predict potential treatment. Future endeavors should focus determining applicability utility metabolomic-derived markers their appropriate implementation large-scale settings.

Language: Английский

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The Critical Role of the Branched Chain Amino Acids (BCAAs) Catabolism-Regulating Enzymes, Branched-Chain Aminotransferase (BCAT) and Branched-Chain α-Keto Acid Dehydrogenase (BCKD), in Human Pathophysiology

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 4022 - 4022

Published: April 5, 2022

Branched chain amino acids (BCAAs), leucine, isoleucine and valine, are essential widely studied for their crucial role in the regulation of protein synthesis mainly through activation mTOR signaling pathway emerging recognition as players various physiological metabolic processes, such glucose homeostasis. BCAA supplementation is primarily used a beneficial nutritional intervention chronic liver kidney disease well muscle wasting disorders. However, downregulated/upregulated plasma BCAAs defective catabolism tissues, due to altered enzymatic activity first two enzymes catabolic pathway, aminotransferase (BCAT) branched-chain α-keto acid dehydrogenase (BCKD), have been investigated many states. The current review focused on underlying mechanisms its contribution pathogenesis numerous pathological conditions diabetes, heart failure cancer. In addition, we summarize findings that indicate recovery dysregulated may be associated with an improved outcome prevention serious complications.

Language: Английский

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Cardiovascular Disease and Alzheimer's Disease: The Heart–Brain Axis

Journal of the American Heart Association, Journal Year: 2023, Volume and Issue: 12(21)

Published: Nov. 6, 2023

Cardiovascular disease (CVD) remains one of the leading causes morbidity and mortality in aging adults across United States. Prior studies indicate that presence atherosclerosis, pathogenic basis CVD, is linked with dementias. Alzheimer's (AD) AD-related dementias are a major public health challenge Recent ≈3.7 million Americans ≥65 years age had clinical AD 2017, projected increases to 9.3 by 2060. Treatment options for remain limited. Development disease-modifying therapies challenging due, part, long preclinical window AD. The incubation period starts midlife, providing critical identification optimization risk factors. Studies link CVD factors such as hypertension, inflammation, dyslipidemia. Both progressive diseases decades-long development periods. can clinically manifest several earlier than AD, making its potential predictor future current review focuses on state literature molecular metabolic pathways modulating heart-brain axis underlying association midlife their effect related Further, we explore CVD/dementia preventive strategies during opportunity research field multiomics novel biomarker use era.

Language: Английский

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Cardiovascular System

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 86

Published: Jan. 1, 2025

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