scholarly journals Lessons Learned from Inherited Metabolic Disorders of Sulfur-Containing Amino Acids Metabolism

2020 ◽  
Vol 150 (Supplement_1) ◽  
pp. 2506S-2517S ◽  
Author(s):  
Viktor Kožich ◽  
Sally Stabler
Keyword(s):  
Amino Acids ◽  
Megaloblastic Anemia ◽  
Genetic Disorders ◽  
Lessons Learned ◽  
Metabolic Changes ◽  
B Vitamins ◽  
Enzyme Replacement ◽  
Increased Risk ◽  
Biallelic Mutations ◽  
Sulfur Containing

ABSTRACT The metabolism of sulfur-containing amino acids (SAAs) requires an orchestrated interplay among several dozen enzymes and transporters, and an adequate dietary intake of methionine (Met), cysteine (Cys), and B vitamins. Known human genetic disorders are due to defects in Met demethylation, homocysteine (Hcy) remethylation, or cobalamin and folate metabolism, in Hcy transsulfuration, and Cys and hydrogen sulfide (H2S) catabolism. These disorders may manifest between the newborn period and late adulthood by a combination of neuropsychiatric abnormalities, thromboembolism, megaloblastic anemia, hepatopathy, myopathy, and bone and connective tissue abnormalities. Biochemical features include metabolite deficiencies (e.g. Met, S-adenosylmethionine (AdoMet), intermediates in 1-carbon metabolism, Cys, or glutathione) and/or their accumulation (e.g. S-adenosylhomocysteine, Hcy, H2S, or sulfite). Treatment should be started as early as possible and may include a low-protein/low-Met diet with Cys-enriched amino acid supplements, pharmacological doses of B vitamins, betaine to stimulate Hcy remethylation, the provision of N-acetylcysteine or AdoMet, or experimental approaches such as liver transplantation or enzyme replacement therapy. In several disorders, patients are exposed to long-term markedly elevated Met concentrations. Although these conditions may inform on Met toxicity, interpretation is difficult due to the presence of additional metabolic changes. Two disorders seem to exhibit Met-associated toxicity in the brain. An increased risk of demyelination in patients with Met adenosyltransferase I/III (MATI/III) deficiency due to biallelic mutations in the MATIA gene has been attributed to very high blood Met concentrations (typically >800 μmol/L) and possibly also to decreased liver AdoMet synthesis. An excessively high Met concentration in some patients with cystathionine β-synthase deficiency has been associated with encephalopathy and brain edema, and direct toxicity of Met has been postulated. In summary, studies in patients with various disorders of SAA metabolism showed complex metabolic changes with distant cellular consequences, most of which are not attributable to direct Met toxicity.

scholarly journals Diabetes Leads to Alterations in Normal Metabolic Transitions of Pregnancy as Revealed by Time-Course Metabolomics

Metabolites ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 350 ◽  
Author(s):  
Jacquelyn M. Walejko ◽  
Anushka Chelliah ◽  
Maureen Keller-Wood ◽  
Clive Wasserfall ◽  
Mark Atkinson ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cord Blood ◽  
Time Course ◽  
Tca Cycle ◽  
Metabolic Changes ◽  
Increased Risk ◽  
Management And Development ◽  
Branched Chain ◽  
Tca Cycle Intermediates ◽  
Poor Outcomes

Women with diabetes during pregnancy are at increased risk of poor maternal and neonatal outcomes. Despite this, the effects of pre-gestational (PGDM) or gestational diabetes (GDM) on metabolism during pregnancy are not well understood. In this study, we utilized metabolomics to identify serum metabolic changes in women with and without diabetes during pregnancy and the cord blood at birth. We observed elevations in tricarboxylic acid (TCA) cycle intermediates, carbohydrates, ketones, and lipids, and a decrease in amino acids across gestation in all individuals. In early gestation, PGDM had elevations in branched-chain amino acids and sugars compared to controls, whereas GDM had increased lipids and decreased amino acids during pregnancy. In both GDM and PGDM, carbohydrate and amino acid pathways were altered, but in PGDM, hemoglobin A1c and isoleucine were significantly increased compared to GDM. Cord blood from GDM and PGDM newborns had similar increases in carbohydrates and choline metabolism compared to controls, and these alterations were not maternal in origin. Our results revealed that PGDM and GDM have distinct metabolic changes during pregnancy. A better understanding of diabetic metabolism during pregnancy can assist in improved management and development of therapeutics and help mitigate poor outcomes in both the mother and newborn.

Methionine-Specific Staining of Collagen

1982 ◽  
Vol 40 ◽  
pp. 294-295
Author(s):  
E.M. Kuhn ◽  
K.D. Marenus ◽  
M. Beer
Keyword(s):  
Amino Acids ◽  
Collagen Fibers ◽  
Type Iii Collagen ◽  
Type I ◽  
Electron Microscopic ◽  
Good Correspondence ◽  
Specific Staining ◽  
Type Iii ◽  
Different Types ◽  
Sulfur Containing

Fibers composed of different types of collagen cannot be differentiated by conventional electron microscopic stains. We are developing staining procedures aimed at identifying collagen fibers of different types.Pt(Gly-L-Met)Cl binds specifically to sulfur-containing amino acids. Different collagens have methionine (met) residues at somewhat different positions. A good correspondence has been reported between known met positions and Pt(GLM) bands in rat Type I SLS (collagen aggregates in which molecules lie adjacent to each other in exact register). We have confirmed this relationship in Type III collagen SLS (Fig. 1).

scholarly journals Safer primary healthcare facilities are needed to protect healthcare workers and maintain essential services: lessons learned from a multicountry COVID-19 emergency response initiative

2021 ◽  
Vol 6 (6) ◽  
pp. e005833
Author(s):  
Leena N Patel ◽  
Samantha Kozikott ◽  
Rodrigue Ilboudo ◽  
Moreen Kamateeka ◽  
Mohammed Lamorde ◽  
...  
Keyword(s):  
Health Facility ◽  
Healthcare Workers ◽  
National Level ◽  
Lessons Learned ◽  
Health Facilities ◽  
Infection Prevention And Control ◽  
Health Facility Level ◽  
Ensure Patient Safety ◽  
Increased Risk ◽  
Facility Level

Healthcare workers (HCWs) are at increased risk of infection from SARS-CoV-2 and other disease pathogens, which take a disproportionate toll on HCWs, with substantial cost to health systems. Improved infection prevention and control (IPC) programmes can protect HCWs, especially in resource-limited settings where the health workforce is scarcest, and ensure patient safety and continuity of essential health services. In response to the COVID-19 pandemic, we collaborated with ministries of health and development partners to implement an emergency initiative for HCWs at the primary health facility level in 22 African countries. Between April 2020 and January 2021, the initiative trained 42 058 front-line HCWs from 8444 health facilities, supported longitudinal supervision and monitoring visits guided by a standardised monitoring tool, and provided resources including personal protective equipment (PPE). We documented significant short-term improvements in IPC performance, but gaps remain. Suspected HCW infections peaked at 41.5% among HCWs screened at monitored facilities in July 2020 during the first wave of the pandemic in Africa. Disease-specific emergency responses are not the optimal approach. Comprehensive, sustainable IPC programmes are needed. IPC needs to be incorporated into all HCW training programmes and combined with supportive supervision and mentorship. Strengthened data systems on IPC are needed to guide improvements at the health facility level and to inform policy development at the national level, along with investments in infrastructure and sustainable supplies of PPE. Multimodal strategies to improve IPC are critical to make health facilities safer and to protect HCWs and the communities they serve.

scholarly journals Current recommendations for clinical surveillance and genetic testing in rhabdoid tumor predisposition: a report from the SIOPE Host Genome Working Group

2021 ◽  
Author(s):  
M. C. Frühwald ◽  
K. Nemes ◽  
H. Boztug ◽  
M. C. A. Cornips ◽  
D. G. Evans ◽  
...  
Keyword(s):  
Working Group ◽  
Soft Part ◽  
Genetic Disorders ◽  
Panel Discussion ◽  
Rhabdoid Tumor ◽  
Host Genome ◽  
Cancer Surveillance ◽  
Malignant Neoplasms ◽  
Pathogenic Variants ◽  
Increased Risk

AbstractThe rhabdoid tumor (RT) predisposition syndromes 1 and 2 (RTPS1 and 2) are rare genetic conditions rendering young children vulnerable to an increased risk of RT, malignant neoplasms affecting the kidney, miscellaneous soft-part tissues, the liver and the central nervous system (Atypical Teratoid Rhabdoid Tumors, ATRT). Both, RTPS1&2 are due to pathogenic variants (PV) in genes encoding constituents of the BAF chromatin remodeling complex, i.e. SMARCB1 (RTPS1) and SMARCA4 (RTPS2). In contrast to other genetic disorders related to PVs in SMARCB1 and SMARCA4 such as Coffin-Siris Syndrome, RTPS1&2 are characterized by a predominance of truncating PVs, terminating transcription thus explaining a specific cancer risk. The penetrance of RTPS1 early in life is high and associated with a poor survival. However, few unaffected carriers may be encountered. Beyond RT, the tumor spectrum may be larger than initially suspected, and cancer surveillance offered to unaffected carriers (siblings or parents) and long-term survivors of RT is still a matter of discussion. RTPS2 exposes female carriers to an ill-defined risk of small cell carcinoma of the ovaries, hypercalcemic type (SCCOHT), which may appear in prepubertal females. RT surveillance protocols for these rare families have not been established. To address unresolved issues in the care of individuals with RTPS and to propose appropriate surveillance guidelines in childhood, the SIOPe Host Genome working group invited pediatric oncologists and geneticists to contribute to an expert meeting. The current manuscript summarizes conclusions of the panel discussion, including consented statements as well as non-evidence-based proposals for validation in the future.

scholarly journals Ingesting a pre-workout supplement containing caffeine, B-vitamins, amino acids, creatine, and beta-alanine before exercise delays fatigue while improving reaction time and muscular endurance

2012 ◽  
Vol 9 (1) ◽  
pp. 28 ◽  
Author(s):  
Brandon D Spradley ◽  
Kristy R Crowley ◽  
Chih-Yin Tai ◽  
Kristina L Kendall ◽  
David H Fukuda ◽  
...  
Keyword(s):  
Amino Acids ◽  
Reaction Time ◽  
B Vitamins ◽  
Muscular Endurance ◽  
Beta Alanine

scholarly journals Plasma Branched-Chain Amino Acids and Incident Cardiovascular Disease in the PREDIMED Trial

2016 ◽  
Vol 62 (4) ◽  
pp. 582-592 ◽  
Author(s):  
Miguel Ruiz-Canela ◽  
Estefania Toledo ◽  
Clary B Clish ◽  
Adela Hruby ◽  
Liming Liang ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Amino Acids ◽  
Cardiovascular Death ◽  
Branched Chain Amino Acids ◽  
Control Group ◽  
Cvd Risk ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Branched Chain

Abstract BACKGROUND The role of branched-chain amino acids (BCAAs) in cardiovascular disease (CVD) remains poorly understood. We hypothesized that baseline BCAA concentrations predict future risk of CVD and that a Mediterranean diet (MedDiet) intervention may counteract this effect. METHODS We developed a case-cohort study within the Prevención con Dieta Mediterránea (PREDIMED), with 226 incident CVD cases and 744 noncases. We used LC-MS/MS to measure plasma BCAAs (leucine, isoleucine, and valine), both at baseline and after 1 year of follow-up. The primary outcome was a composite of incident stroke, myocardial infarction, or cardiovascular death. RESULTS After adjustment for potential confounders, baseline leucine and isoleucine concentrations were associated with higher CVD risk: the hazard ratios (HRs) for the highest vs lowest quartile were 1.70 (95% CI, 1.05–2.76) and 2.09 (1.27–3.44), respectively. Stronger associations were found for stroke. For both CVD and stroke, we found higher HRs across successive quartiles of BCAAs in the control group than in the MedDiet groups. With stroke as the outcome, a significant interaction (P = 0.009) between baseline BCAA score and intervention with MedDiet was observed. No significant effect of the intervention on 1-year changes in BCAAs or any association between 1-year changes in BCAAs and CVD were observed. CONCLUSIONS Higher concentrations of baseline BCAAs were associated with increased risk of CVD, especially stroke, in a high cardiovascular risk population. A Mediterranean-style diet had a negligible effect on 1-year changes in BCAAs, but it may counteract the harmful effects of BCAAs on stroke.

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