A5074687178- Metabolism and Genetic Disorders
- Metabolomics and Mass Spectrometry Studies
- Mitochondrial Function and Pathology
- Neonatal Health and Biochemistry
- Diet and metabolism studies
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cutaneous lymphoproliferative disorders research
- Pancreatic and Hepatic Oncology Research
- Healthcare and Venom Research
- melanin and skin pigmentation
- Pharmacological Effects of Natural Compounds
- Liver Disease Diagnosis and Treatment
- Pediatric Hepatobiliary Diseases and Treatments
- T-cell and Retrovirus Studies
- Ion Transport and Channel Regulation
- Telomeres, Telomerase, and Senescence
- Genetic and Kidney Cyst Diseases
- Occupational and environmental lung diseases
- Biochemical effects in animals
- Muscle and Compartmental Disorders
- Lysosomal Storage Disorders Research
- Analytical Chemistry and Chromatography
National Human Genome Research Institute
2010-2025
Children's National
2023-2024
Case Western Reserve University
2014-2018
University School
2014
National Institutes of Health
2010
University of Hertfordshire
2010
High concentrations of propionate and its metabolites are found in several diseases that often associated with the development cardiac dysfunction, such as obesity, diabetes, propionic acidemia, methylmalonic acidemia. In present work, we employed a stable isotope-based metabolic flux approach to understand propionate-mediated perturbation energy metabolism. Propionate led accumulation propionyl-CoA (increased by ~101-fold) methylmalonyl-CoA 36-fold). This caused significant mitochondrial...
Propionate, 3-hydroxypropionate (3HP), methylcitrate, related compounds, and ammonium accumulate in body fluids of patients with disorders propionyl-CoA metabolism, such as propionic acidemia. Although liver transplantation alleviates hyperammonemia, high concentrations propionate, 3HP, methylcitrate persist fluids. We hypothesized that conserved metabolic perturbations occurring transplanted result from the simultaneous presence propionate 3HP investigated inter-relations metabolism...
The RAB27A/Melanophilin/Myosin-5a tripartite protein complex is required for capturing mature melanosomes in the peripheral actin network of melanocytes subsequent transfer to keratinocytes. Mutations any one member this cause three forms Griscelli syndrome (GS), each with distinct clinical features but a similar cellular phenotype. To date, only case GS type III (GSIII), caused by mutations Melanophilin (MLPH) gene, has been reported. Here, we report seven new cases GSIII Arab pedigrees....
Pyruvate dehydrogenase complex deficiencies (PDCDs) and other mitochondrial disorders (MtDs) can (a) result in congenital lactic acidosis with elevations of blood alanine (Ala) proline (Pro), (b) lead to decreased ATP production, (c) high morbidity mortality. With ~140,000 live births annually Ohio ~1 9,000 overall prevalence MtDs, we estimate 2 3 newborns will have PDCD 13 14 others likely another MtD annually. We compared the sensitivities plasma amino acids (AA) Alanine (Ala),...
Beta‐alanine (BA) is a product of uracil and 3‐hydroxypropionate catabolism. BA precursor the dipeptides carnosine anserine, which play an important role in pH homeostasis muscle during exercise. used by athletes as nutritional supplement to increase performance strenuous However, unwanted side‐effect ingestion unpleasant paresthesia, mechanism unknown. As part study metabolism, we perfused rat livers with 2 mM [ 15 N, 13 C 3 ]BA (M4 BA). A metabolomic liver showed that acetyl‐CoA was 12% M2...
Abstract Objectives An assessment of amino acid and amine concentrations is important for the diagnosis management inborn errors metabolism (IEMs). Methods exist that measure these biologically metabolites but are cost-prohibitive and/or time consuming. We therefore sought to develop a novel methodology, applicable IEMs, both high-throughput low cost. Previously, we developed methodology rapid, repeatable, cost-efficient separation approximately 20 amines as proof concept now expand it...
Propionic acidemia (PA) is a rare autosomal recessive disorder leading to inhibition of propionate entering an anaplerotic pathway, via propionyl-CoA, the citric acid cycle (CAC). PA characterized by defect in conversion propionyl-CoA methylmalonyl-CoA through carboxylase (PCC). Decreased activity PCC shunts into alternative metabolic pathways forming 3-hydroxypropionate (HPA), which increases concentration toxic levels. We investigated fates HPA rat livers and heart using combination...
Propionic acidemia (PA) is a rare autosomal recessive disorder leading to inhibition of propionate entering an anaplerotic pathway, via propionyl‐CoA, the citric acid cycle (CAC). PA characterized by defect in conversion propionyl‐CoA methylmalonyl‐CoA through carboxylase (PCC). Decreased activity PCC shunts into alternative metabolic pathways forming 3‐hydroxypropionate (3‐HPA), which increases concentration toxic levels. We investigated fates 3‐HPA rat livers using combination metabolomics...