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Guofang Zhang

Associate Professor in Medicine
Medicine, Endocrinology, Metabolism, and Nutrition
DUMC Box 104775, Durham, NC 27710
300 North Duke Street, Durham, NC 27701

Selected Publications


BCAA-nitrogen flux in brown fat controls metabolic health independent of thermogenesis.

Journal Article Cell · May 9, 2024 Brown adipose tissue (BAT) is best known for thermogenesis. Rodent studies demonstrated that enhanced BAT thermogenesis is tightly associated with increased energy expenditure, reduced body weight, and improved glucose homeostasis. However, human BAT is pr ... Full text Link to item Cite

High Doses of Exogenous Glucagon Stimulate Insulin Secretion and Reduce Insulin Clearance in Healthy Humans.

Journal Article Diabetes · March 1, 2024 Glucagon is generally defined as a counterregulatory hormone with a primary role to raise blood glucose concentrations by increasing endogenous glucose production (EGP) in response to hypoglycemia. However, glucagon has long been known to stimulate insulin ... Full text Link to item Cite

Ketone flux through BDH1 supports metabolic remodeling of skeletal and cardiac muscles in response to intermittent time-restricted feeding.

Journal Article Cell Metab · February 6, 2024 Time-restricted feeding (TRF) has gained attention as a dietary regimen that promotes metabolic health. This study questioned if the health benefits of an intermittent TRF (iTRF) schedule require ketone flux specifically in skeletal and cardiac muscles. No ... Full text Link to item Cite

APOL1-mediated monovalent cation transport contributes to APOL1-mediated podocytopathy in kidney disease.

Journal Article J Clin Invest · January 16, 2024 Two coding variants of apolipoprotein L1 (APOL1), called G1 and G2, explain much of the excess risk of kidney disease in African Americans. While various cytotoxic phenotypes have been reported in experimental models, the proximal mechanism by which G1 and ... Full text Link to item Cite

Pathophysiological mechanisms of complications associated with propionic acidemia.

Journal Article Pharmacol Ther · September 2023 Propionic acidemia (PA) is a genetic metabolic disorder caused by mutations in the mitochondrial enzyme, propionyl-CoA carboxylase (PCC), which is responsible for converting propionyl-CoA to methylmalonyl-CoA for further metabolism in the tricarboxylic aci ... Full text Link to item Cite

Prevalence of propionic acidemia in China.

Journal Article Orphanet journal of rare diseases · September 2023 Propionic acidemia (PA) is a rare autosomal recessive congenital disease caused by mutations in the PCCA or PCCB genes. Elevated propionylcarnitine, 2-methylcitric acid (2MCA), propionylglycine, glycine and 3-hydroxypropionate can be used to diagnose PA. E ... Full text Cite

Glutathione limits RUNX2 oxidation and degradation to regulate bone formation.

Journal Article JCI Insight · August 22, 2023 Reactive oxygen species (ROS) are natural products of mitochondrial oxidative metabolism and oxidative protein folding. ROS levels must be well controlled, since elevated ROS has been shown to have deleterious effects on osteoblasts. Moreover, excessive RO ... Full text Link to item Cite

A high-fat diet increases hepatic mitochondrial turnover through restricted acetylation in a NAFLD mouse model.

Journal Article Am J Physiol Endocrinol Metab · July 1, 2023 Lysine acetylation of proteins has emerged as a key posttranslational modification (PTM) that regulates mitochondrial metabolism. Acetylation may regulate energy metabolism by inhibiting and affecting the stability of metabolic enzymes and oxidative phosph ... Full text Link to item Cite

Pyruvate-supported flux through medium-chain ketothiolase promotes mitochondrial lipid tolerance in cardiac and skeletal muscles.

Journal Article Cell Metab · June 6, 2023 Even-chain acylcarnitine (AC) metabolites, most of which are generated as byproducts of incomplete fatty acid oxidation (FAO), are viewed as biomarkers of mitochondrial lipid stress attributable to one or more metabolic bottlenecks in the β-oxidation pathw ... Full text Link to item Cite

Ischemia promotes acyl-CoAs dephosphorylation and propionyl-CoA accumulation.

Journal Article Metabolomics · February 7, 2023 INTRODUCTION: Our untargeted metabolic data unveiled that Acyl-CoAs undergo dephosphorylation, however little is known about these novel metabolites and their physiology/pathology relevance. OBJECTIVES: To understand the relationship between acyl-CoAs deph ... Full text Link to item Cite

Tirzepatide induces a thermogenic-like amino acid signature in brown adipose tissue.

Journal Article Mol Metab · October 2022 OBJECTIVES: Tirzepatide, a dual GIP and GLP-1 receptor agonist, delivered superior glycemic control and weight loss compared to selective GLP-1 receptor (GLP-1R) agonism in patients with type 2 diabetes (T2D). These results have fueled mechanistic studies ... Full text Link to item Cite

Paradoxical activation of transcription factor SREBP1c and de novo lipogenesis by hepatocyte-selective ATP-citrate lyase depletion in obese mice.

Journal Article J Biol Chem · October 2022 Hepatic steatosis associated with high-fat diet, obesity, and type 2 diabetes is thought to be the major driver of severe liver inflammation, fibrosis, and cirrhosis. Cytosolic acetyl CoA (AcCoA), a central metabolite and substrate for de novo lipogenesis ... Full text Link to item Cite

The intestine is a major contributor to circulating succinate in mice.

Journal Article FASEB J · October 2022 The tricarboxylic acid (TCA) cycle is the epicenter of cellular aerobic metabolism. TCA cycle intermediates facilitate energy production and provide anabolic precursors, but also function as intra- and extracellular metabolic signals regulating pleiotropic ... Full text Link to item Cite

Statin therapy inhibits fatty acid synthase via dynamic protein modifications.

Journal Article Nat Commun · May 10, 2022 Statins are a class of drug widely prescribed for the prevention of cardiovascular disease, with pleiotropic cellular effects. Statins inhibit HMG-CoA reductase (HMGCR), which converts the metabolite HMG-CoA into mevalonate. Recent discoveries have shown H ... Full text Link to item Cite

Distinct Roles of Glutamine Metabolism in Benign and Malignant Cartilage Tumors With IDH Mutations.

Journal Article J Bone Miner Res · May 2022 Enchondromas and chondrosarcomas are common cartilage neoplasms that are either benign or malignant, respectively. The majority of these tumors harbor mutations in either IDH1 or IDH2. Glutamine metabolism has been implicated as a critical regulator of tum ... Full text Link to item Cite

SLC38A2 provides proline to fulfill unique synthetic demands arising during osteoblast differentiation and bone formation.

Journal Article Elife · March 9, 2022 Cellular differentiation is associated with the acquisition of a unique protein signature that is essential to attain the ultimate cellular function and activity of the differentiated cell. This is predicted to result in unique biosynthetic demands that ar ... Full text Link to item Cite

Overcompensation of CoA Trapping by Di(2-ethylhexyl) Phthalate (DEHP) Metabolites in Livers of Wistar Rats.

Journal Article Int J Mol Sci · December 16, 2021 Di(2-ethylhexyl) phthalate (DEHP) is commonly used as a plasticizer in various industrial and household plastic products, ensuring widespread human exposures. Its routine detection in human bio-fluids and the propensity of its monoester metabolite to activ ... Full text Link to item Cite

Metabolic perturbations mediated by propionyl-CoA accumulation in organs of mouse model of propionic acidemia.

Journal Article Mol Genet Metab · November 2021 Propionic acidemia (PA) is an autosomal recessive metabolic disorder after gene encoding propionyl-CoA carboxylase, Pcca or Pccb, is mutated. This genetic disorder could develop various complications which are ascribed to dysregulated propionyl-CoA metabol ... Full text Link to item Cite

BCAA-nitrogen flux in brown fat controls metabolic health independent of thermogenesis.

Journal Article Cell · May 9, 2024 Brown adipose tissue (BAT) is best known for thermogenesis. Rodent studies demonstrated that enhanced BAT thermogenesis is tightly associated with increased energy expenditure, reduced body weight, and improved glucose homeostasis. However, human BAT is pr ... Full text Link to item Cite

High Doses of Exogenous Glucagon Stimulate Insulin Secretion and Reduce Insulin Clearance in Healthy Humans.

Journal Article Diabetes · March 1, 2024 Glucagon is generally defined as a counterregulatory hormone with a primary role to raise blood glucose concentrations by increasing endogenous glucose production (EGP) in response to hypoglycemia. However, glucagon has long been known to stimulate insulin ... Full text Link to item Cite

Ketone flux through BDH1 supports metabolic remodeling of skeletal and cardiac muscles in response to intermittent time-restricted feeding.

Journal Article Cell Metab · February 6, 2024 Time-restricted feeding (TRF) has gained attention as a dietary regimen that promotes metabolic health. This study questioned if the health benefits of an intermittent TRF (iTRF) schedule require ketone flux specifically in skeletal and cardiac muscles. No ... Full text Link to item Cite

APOL1-mediated monovalent cation transport contributes to APOL1-mediated podocytopathy in kidney disease.

Journal Article J Clin Invest · January 16, 2024 Two coding variants of apolipoprotein L1 (APOL1), called G1 and G2, explain much of the excess risk of kidney disease in African Americans. While various cytotoxic phenotypes have been reported in experimental models, the proximal mechanism by which G1 and ... Full text Link to item Cite

Pathophysiological mechanisms of complications associated with propionic acidemia.

Journal Article Pharmacol Ther · September 2023 Propionic acidemia (PA) is a genetic metabolic disorder caused by mutations in the mitochondrial enzyme, propionyl-CoA carboxylase (PCC), which is responsible for converting propionyl-CoA to methylmalonyl-CoA for further metabolism in the tricarboxylic aci ... Full text Link to item Cite

Prevalence of propionic acidemia in China.

Journal Article Orphanet journal of rare diseases · September 2023 Propionic acidemia (PA) is a rare autosomal recessive congenital disease caused by mutations in the PCCA or PCCB genes. Elevated propionylcarnitine, 2-methylcitric acid (2MCA), propionylglycine, glycine and 3-hydroxypropionate can be used to diagnose PA. E ... Full text Cite

Glutathione limits RUNX2 oxidation and degradation to regulate bone formation.

Journal Article JCI Insight · August 22, 2023 Reactive oxygen species (ROS) are natural products of mitochondrial oxidative metabolism and oxidative protein folding. ROS levels must be well controlled, since elevated ROS has been shown to have deleterious effects on osteoblasts. Moreover, excessive RO ... Full text Link to item Cite

A high-fat diet increases hepatic mitochondrial turnover through restricted acetylation in a NAFLD mouse model.

Journal Article Am J Physiol Endocrinol Metab · July 1, 2023 Lysine acetylation of proteins has emerged as a key posttranslational modification (PTM) that regulates mitochondrial metabolism. Acetylation may regulate energy metabolism by inhibiting and affecting the stability of metabolic enzymes and oxidative phosph ... Full text Link to item Cite

Pyruvate-supported flux through medium-chain ketothiolase promotes mitochondrial lipid tolerance in cardiac and skeletal muscles.

Journal Article Cell Metab · June 6, 2023 Even-chain acylcarnitine (AC) metabolites, most of which are generated as byproducts of incomplete fatty acid oxidation (FAO), are viewed as biomarkers of mitochondrial lipid stress attributable to one or more metabolic bottlenecks in the β-oxidation pathw ... Full text Link to item Cite

Ischemia promotes acyl-CoAs dephosphorylation and propionyl-CoA accumulation.

Journal Article Metabolomics · February 7, 2023 INTRODUCTION: Our untargeted metabolic data unveiled that Acyl-CoAs undergo dephosphorylation, however little is known about these novel metabolites and their physiology/pathology relevance. OBJECTIVES: To understand the relationship between acyl-CoAs deph ... Full text Link to item Cite

Tirzepatide induces a thermogenic-like amino acid signature in brown adipose tissue.

Journal Article Mol Metab · October 2022 OBJECTIVES: Tirzepatide, a dual GIP and GLP-1 receptor agonist, delivered superior glycemic control and weight loss compared to selective GLP-1 receptor (GLP-1R) agonism in patients with type 2 diabetes (T2D). These results have fueled mechanistic studies ... Full text Link to item Cite

Paradoxical activation of transcription factor SREBP1c and de novo lipogenesis by hepatocyte-selective ATP-citrate lyase depletion in obese mice.

Journal Article J Biol Chem · October 2022 Hepatic steatosis associated with high-fat diet, obesity, and type 2 diabetes is thought to be the major driver of severe liver inflammation, fibrosis, and cirrhosis. Cytosolic acetyl CoA (AcCoA), a central metabolite and substrate for de novo lipogenesis ... Full text Link to item Cite

The intestine is a major contributor to circulating succinate in mice.

Journal Article FASEB J · October 2022 The tricarboxylic acid (TCA) cycle is the epicenter of cellular aerobic metabolism. TCA cycle intermediates facilitate energy production and provide anabolic precursors, but also function as intra- and extracellular metabolic signals regulating pleiotropic ... Full text Link to item Cite

Statin therapy inhibits fatty acid synthase via dynamic protein modifications.

Journal Article Nat Commun · May 10, 2022 Statins are a class of drug widely prescribed for the prevention of cardiovascular disease, with pleiotropic cellular effects. Statins inhibit HMG-CoA reductase (HMGCR), which converts the metabolite HMG-CoA into mevalonate. Recent discoveries have shown H ... Full text Link to item Cite

Distinct Roles of Glutamine Metabolism in Benign and Malignant Cartilage Tumors With IDH Mutations.

Journal Article J Bone Miner Res · May 2022 Enchondromas and chondrosarcomas are common cartilage neoplasms that are either benign or malignant, respectively. The majority of these tumors harbor mutations in either IDH1 or IDH2. Glutamine metabolism has been implicated as a critical regulator of tum ... Full text Link to item Cite

SLC38A2 provides proline to fulfill unique synthetic demands arising during osteoblast differentiation and bone formation.

Journal Article Elife · March 9, 2022 Cellular differentiation is associated with the acquisition of a unique protein signature that is essential to attain the ultimate cellular function and activity of the differentiated cell. This is predicted to result in unique biosynthetic demands that ar ... Full text Link to item Cite

Overcompensation of CoA Trapping by Di(2-ethylhexyl) Phthalate (DEHP) Metabolites in Livers of Wistar Rats.

Journal Article Int J Mol Sci · December 16, 2021 Di(2-ethylhexyl) phthalate (DEHP) is commonly used as a plasticizer in various industrial and household plastic products, ensuring widespread human exposures. Its routine detection in human bio-fluids and the propensity of its monoester metabolite to activ ... Full text Link to item Cite

Metabolic perturbations mediated by propionyl-CoA accumulation in organs of mouse model of propionic acidemia.

Journal Article Mol Genet Metab · November 2021 Propionic acidemia (PA) is an autosomal recessive metabolic disorder after gene encoding propionyl-CoA carboxylase, Pcca or Pccb, is mutated. This genetic disorder could develop various complications which are ascribed to dysregulated propionyl-CoA metabol ... Full text Link to item Cite

SLC1A5 provides glutamine and asparagine necessary for bone development in mice.

Journal Article Elife · October 14, 2021 Osteoblast differentiation is sequentially characterized by high rates of proliferation followed by increased protein and matrix synthesis, processes that require substantial amino acid acquisition and production. How osteoblasts obtain or maintain intrace ... Full text Link to item Cite

Distinct roles of glutamine metabolism in benign and malignant cartilage tumors with IDH mutations

Journal Article · September 13, 2021 AbstractEnchondromas and chondrosarcomas are common cartilage neoplasms that are either benign or malignant respectively. The majority of these tumors harbor mutations in either IDH1 or Full text Cite

Reductive TCA cycle metabolism fuels glutamine- and glucose-stimulated insulin secretion.

Journal Article Cell metabolism · April 2021 Metabolic fuels regulate insulin secretion by generating second messengers that drive insulin granule exocytosis, but the biochemical pathways involved are incompletely understood. Here we demonstrate that stimulation of rat insulinoma cells or primary rat ... Full text Cite

Mutant IDH and non-mutant chondrosarcomas display distinct cellular metabolomes.

Journal Article Cancer Metab · March 24, 2021 BACKGROUND: Majority of chondrosarcomas are associated with a number of genetic alterations, including somatic mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 genes, but the downstream effects of these mutated enzymes on cellular metabolism and tum ... Full text Link to item Cite

Branched-chain α-ketoacids are preferentially reaminated and activate protein synthesis in the heart.

Journal Article Nat Commun · March 15, 2021 Branched-chain amino acids (BCAA) and their cognate α-ketoacids (BCKA) are elevated in an array of cardiometabolic diseases. Here we demonstrate that the major metabolic fate of uniformly-13C-labeled α-ketoisovalerate ([U-13C]KIV) in the heart is reaminati ... Full text Link to item Cite

Measuring acetyl-CoA and acetylated histone turnover in vivo: Effect of a high fat diet.

Journal Article Anal Biochem · February 15, 2021 Cellular availability of acetyl-CoA, a central intermediate of metabolism, regulates histone acetylation. The impact of a high-fat diet (HFD) on the turnover rates of acetyl-CoA and acetylated histones is unknown. We developed a method for simultaneous mea ... Full text Link to item Cite

Author Correction: Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer.

Journal Article Nat Med · June 2020 An amendment to this paper has been published and can be accessed via a link at the top of the paper. ... Full text Link to item Cite

Dietary branched-chain amino acid restriction alters fuel selection and reduces triglyceride stores in hearts of Zucker fatty rats.

Journal Article Am J Physiol Endocrinol Metab · February 1, 2020 Elevations in circulating levels of branched-chain amino acids (BCAAs) are associated with a variety of cardiometabolic diseases and conditions. Restriction of dietary BCAAs in rodent models of obesity lowers circulating BCAA levels and improves whole-anim ... Full text Link to item Cite

Glutamine Metabolism in Cartilage Tumors

Conference JOURNAL OF BONE AND MINERAL RESEARCH · 2020 Cite

Glutamine Metabolism Regulates Proliferation and Lineage Allocation in Skeletal Stem Cells.

Journal Article Cell Metab · April 2, 2019 Skeletal stem cells (SSCs) are postulated to provide a continuous supply of osteoblasts throughout life. However, under certain conditions, the SSC population can become incorrectly specified or is not maintained, resulting in reduced osteoblast formation, ... Full text Link to item Cite

Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer.

Journal Article Nat Med · April 2019 Pancreatic ductal adenocarcinoma (PDAC) is characterized by KRAS- and autophagy-dependent tumorigenic growth, but the role of KRAS in supporting autophagy has not been established. We show that, to our surprise, suppression of KRAS increased autophagic flu ... Full text Link to item Cite

Propionate-induced changes in cardiac metabolism, notably CoA trapping, are not altered by l-carnitine.

Journal Article Am J Physiol Endocrinol Metab · October 1, 2018 High concentrations of propionate and its metabolites are found in several diseases that are often associated with the development of cardiac dysfunction, such as obesity, diabetes, propionic acidemia, and methylmalonic acidemia. In the present work, we em ... Full text Link to item Cite

Quantifying ceramide kinetics in vivo using stable isotope tracers and LC-MS/MS.

Journal Article Am J Physiol Endocrinol Metab · September 1, 2018 Numerous studies have implicated dyslipidemia as a key factor in mediating insulin resistance. Ceramides have received special attention since their levels are inversely associated with normal insulin signaling and positively associated with factors that a ... Full text Link to item Cite

Aldolase B-Mediated Fructose Metabolism Drives Metabolic Reprogramming of Colon Cancer Liver Metastasis.

Journal Article Cell Metab · June 5, 2018 Cancer metastasis accounts for the majority of cancer-related deaths and remains a clinical challenge. Metastatic cancer cells generally resemble cells of the primary cancer, but they may be influenced by the milieu of the organs they colonize. Here, we sh ... Full text Link to item Cite

The BCKDH Kinase and Phosphatase Integrate BCAA and Lipid Metabolism via Regulation of ATP-Citrate Lyase.

Journal Article Cell Metab · June 5, 2018 Branched-chain amino acids (BCAA) are strongly associated with dysregulated glucose and lipid metabolism, but the underlying mechanisms are poorly understood. We report that inhibition of the kinase (BDK) or overexpression of the phosphatase (PPM1K) that r ... Full text Link to item Cite

Cardiovascular Metabolomics.

Journal Article Circ Res · April 27, 2018 Disturbances in cardiac metabolism underlie most cardiovascular diseases. Metabolomics, one of the newer omics technologies, has emerged as a powerful tool for defining changes in both global and cardiac-specific metabolism that occur across a spectrum of ... Full text Link to item Cite

Inter-relations between 3-hydroxypropionate and propionate metabolism in rat liver: relevance to disorders of propionyl-CoA metabolism.

Journal Article Am J Physiol Endocrinol Metab · October 1, 2017 Propionate, 3-hydroxypropionate (3HP), methylcitrate, related compounds, and ammonium accumulate in body fluids of patients with disorders of propionyl-CoA metabolism, such as propionic acidemia. Although liver transplantation alleviates hyperammonemia, hi ... Full text Link to item Cite

Glutathione species and metabolomic prints in subjects with liver disease as biological markers for the detection of hepatocellular carcinoma.

Journal Article HPB (Oxford) · December 2016 BACKGROUND: The incidence of liver disease is increasing in USA. Animal models had shown glutathione species in plasma reflects liver glutathione state and it could be a surrogate for the detection of hepatocellular carcinoma (HCC). METHODS: The present st ... Full text Link to item Cite

Methylfolate Trap Promotes Bacterial Thymineless Death by Sulfa Drugs.

Journal Article PLoS Pathog · October 2016 The methylfolate trap, a metabolic blockage associated with anemia, neural tube defects, Alzheimer's dementia, cardiovascular diseases, and cancer, was discovered in the 1960s, linking the metabolism of folate, vitamin B12, methionine and homocysteine. How ... Full text Link to item Cite

Glutamine Metabolism Regulates the Pluripotency Transcription Factor OCT4.

Journal Article Cell Rep · July 12, 2016 The molecular mechanisms underlying the regulation of pluripotency by cellular metabolism in human embryonic stem cells (hESCs) are not fully understood. We found that high levels of glutamine metabolism are essential to prevent degradation of OCT4, a key ... Full text Link to item Cite

A Western diet induced NAFLD in LDLR(-/)(-) mice is associated with reduced hepatic glutathione synthesis.

Journal Article Free Radic Biol Med · July 2016 Oxidative stress plays a key role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Glutathione is the major anti-oxidant involved in cellular oxidative defense, however there are currently no simple non-invasive methods for assessing hepat ... Full text Link to item Cite

Oncogenic PIK3CA mutations reprogram glutamine metabolism in colorectal cancer.

Journal Article Nat Commun · June 20, 2016 Cancer cells often require glutamine for growth, thereby distinguishing them from most normal cells. Here we show that PIK3CA mutations reprogram glutamine metabolism by upregulating glutamate pyruvate transaminase 2 (GPT2) in colorectal cancer (CRC) cells ... Full text Link to item Cite

Compartmentation of Metabolism of the C12-, C9-, and C5-n-dicarboxylates in Rat Liver, Investigated by Mass Isotopomer Analysis: ANAPLEROSIS FROM DODECANEDIOATE.

Journal Article J Biol Chem · July 24, 2015 We investigated the compartmentation of the catabolism of dodecanedioate (DODA), azelate, and glutarate in perfused rat livers, using a combination of metabolomics and mass isotopomer analyses. Livers were perfused with recirculating or nonrecirculating bu ... Full text Link to item Cite

Multiple mass isotopomer tracing of acetyl-CoA metabolism in Langendorff-perfused rat hearts: channeling of acetyl-CoA from pyruvate dehydrogenase to carnitine acetyltransferase.

Journal Article J Biol Chem · March 27, 2015 We developed an isotopic technique to assess mitochondrial acetyl-CoA turnover (≈citric acid flux) in perfused rat hearts. Hearts are perfused with buffer containing tracer [(13)C2,(2)H3]acetate, which forms M5 + M4 + M3 acetyl-CoA. The buffer may also con ... Full text Link to item Cite

Identification of S-nitroso-CoA reductases that regulate protein S-nitrosylation.

Journal Article Proc Natl Acad Sci U S A · December 30, 2014 Coenzyme A (CoA) mediates thiol-based acyl-group transfer (acetylation and palmitoylation). However, a role for CoA in the thiol-based transfer of NO groups (S-nitrosylation) has not been considered. Here we describe protein S-nitrosylation in yeast (heret ... Full text Link to item Cite

Catabolism of (2E)-4-hydroxy-2-nonenal via ω- and ω-1-oxidation stimulated by ketogenic diet.

Journal Article J Biol Chem · November 14, 2014 Oxidative stress triggers the peroxidation of ω-6-polyunsaturated fatty acids to reactive lipid fragments, including (2E)-4-hydroxy-2-nonenal (HNE). We previously reported two parallel catabolic pathways of HNE. In this study, we report a novel metabolite ... Full text Link to item Cite

Modular isotopomer synthesis of γ-hydroxybutyric acid for a quantitative analysis of metabolic fates.

Journal Article ACS Chem Biol · August 15, 2014 Herein we report a study combining metabolomics and mass isotopomer analysis used for investigation of the biochemical fate of γ-hydroxybutyric acid (GHB). Using various (13)C incorporation labeling patterns into GHB, we have discovered that GHB is catabol ... Full text Link to item Cite

Glutathionylated 4-hydroxy-2-(E)-alkenal enantiomers in rat organs and their contributions toward the disposal of 4-hydroxy-2-(E)-nonenal in rat liver.

Journal Article Free Radic Biol Med · May 2014 The major route for elimination of 4-hydroxy-2-(E)-nonenal (4-HNE) has long been considered to be through glutathionylation and eventual excretion as a mercapturic acid conjugate. To better quantitate the glutathionylation process, we developed a sensitive ... Full text Link to item Cite

Novel approach in LC-MS/MS using MRM to generate a full profile of acyl-CoAs: discovery of acyl-dephospho-CoAs.

Journal Article J Lipid Res · March 2014 A metabolomic approach to selectively profile all acyl-CoAs was developed using a programmed multiple reaction monitoring (MRM) method in LC-MS/MS and was employed in the analysis of various rat organs. The programmed MRM method possessed 300 mass ion tran ... Full text Link to item Cite

Identification of a negative feedback loop in biological oxidant formation fegulated by 4-hydroxy-2-(E)-nonenal.

Journal Article Redox Biol · 2014 4-Hydroxy-2-(E)-nonenal (4-HNE) is one of the major lipid peroxidation product formed during oxidative stress. At high concentrations, 4-HNE is cytotoxic and exerts deleterious effects that are often associated with the pathology of oxidative stress-driven ... Full text Link to item Cite

Metabolomic analysis of liver tissue from the vx2 rabbit model of secondary liver tumors

Journal Article HPB Surgery · January 1, 2014 Purpose. The incidence of liver neoplasms is rising in USA. The purpose of this study was to determine metabolic profiles of liver tissue during early cancer development. Methods. We used the rabbit VX2 model of liver tumors (LT) and a control group consis ... Full text Cite

4-Hydroxy-2(E)-nonenal (HNE) catabolism and formation of HNE adducts are modulated by β oxidation of fatty acids in the isolated rat heart.

Journal Article Free Radic Biol Med · May 2013 We previously reported that a novel metabolic pathway functionally catabolizes 4-hydroxy-2(E)-nonenal (HNE) via two parallel pathways, which rely heavily on β-oxidation pathways. The hypothesis driving this report is that perturbations of β oxidation will ... Full text Link to item Cite

Metabolomics and mass isotopomer analysis as a strategy for pathway discovery: pyrrolyl and cyclopentenyl derivatives of the pro-drug of abuse, levulinate.

Journal Article Chem Res Toxicol · February 18, 2013 We recently reported that levulinate (4-ketopentanoate) is converted in the liver to 4-hydroxypentanoate, a drug of abuse, and that the formation of 4-hydroxypentanoate is stimulated by ethanol oxidation. We also identified 3 parallel β-oxidation pathways ... Full text Link to item Cite

Identification of n-hydroxy acid metabolites in electron impact ionization mass spectrometry.

Journal Article Rapid Commun Mass Spectrom · June 15, 2012 RATIONALE: The catabolism of 4-hydroxy acid (drugs of abuse and lipid peroxidation products) generates a series of hydroxy acids with different carbon chain lengths and hydroxyl group at different locations. The identification of these hydroxy acid metabol ... Full text Link to item Cite

Metabolism of γ-hydroxybutyrate in perfused rat livers.

Journal Article Biochem J · June 1, 2012 GHB (γ-hydroxybutyrate) is both a neurotransmitter and a drug of abuse (date-rape drug). We investigated the catabolism of this compound in perfused rat livers. Using a combination of metabolomics and mass isotopomer analysis, we showed that GHB is metabol ... Full text Link to item Cite

Dietary regulation of catabolic disposal of 4-hydroxynonenal analogs in rat liver.

Journal Article Free Radic Biol Med · March 15, 2012 Our previous work in perfused rat livers has demonstrated that 4-hydroxynonenal (HNE) is catabolized predominantly via β oxidation. Therefore, we hypothesized that perturbations in β oxidation, such as diet-altered fatty acid oxidation activity, could lead ... Full text Link to item Cite

Metabolomics, pathway regulation, and pathway discovery.

Journal Article J Biol Chem · July 8, 2011 Metabolomics is a data-based research strategy, the aims of which are to identify biomarker pictures of metabolic systems and metabolic perturbations and to formulate hypotheses to be tested. It involves the assay by mass spectrometry or NMR of many metabo ... Full text Link to item Cite

Bacterial conversion of folinic acid is required for antifolate resistance.

Journal Article J Biol Chem · April 29, 2011 Antifolates, which are among the first antimicrobial agents invented, inhibit cell growth by creating an intracellular state of folate deficiency. Clinical resistance to antifolates has been mainly attributed to mutations that alter structure or expression ... Full text Link to item Cite

Isotopomer enrichment assay for very short chain fatty acids and its metabolic applications.

Journal Article Anal Biochem · March 1, 2011 The present work illustrated an accurate GC/MS measurement for the low isotopomer enrichment assay of formic acid, acetic acid, propionic aicd, butyric acid, and pentanoic acid. The pentafluorobenzyl bromide derivatives of these very short chain fatty acid ... Full text Link to item Cite

Metabolism of levulinate in perfused rat livers and live rats: conversion to the drug of abuse 4-hydroxypentanoate.

Journal Article J Biol Chem · February 18, 2011 Calcium levulinate (4-ketopentanoate) is used as an oral and parenteral source of calcium. We hypothesized that levulinate is converted in the liver to 4-hydroxypentanoate, a new drug of abuse, and that this conversion is accelerated by ethanol oxidation. ... Full text Link to item Cite

Disturbances in the glutathione/ophthalmate redox buffer system in the woodchuck model of hepatitis virus-induced hepatocellular carcinoma.

Journal Article HPB Surg · 2011 Purpose. The incidence of liver tumors is rising in USA. The purpose of this study was to evaluate liver oxido-reductive status in the presence of chronic liver disease and hepatocellular carcinoma (HCC). Methods. Glutathione species and ophthalmate (OA) c ... Full text Link to item Cite

Using isotopic tools to dissect and quantitate parallel metabolic pathways.

Journal Article J Am Chem Soc · May 12, 2010 4-Hydroxyacids are ubiquitous in human physiology. They are derived from the drugs of abuse gamma-hydroxybutyrate (GHB), gamma-hydroxypentanoate(GHP), in addition to the omnipresent lipid peroxidation product 4-hydroxy-2-(E)-nonenal (4-HNE). Previously we ... Full text Link to item Cite

Parenteral and enteral metabolism of anaplerotic triheptanoin in normal rats. II. Effects on lipolysis, glucose production, and liver acyl-CoA profile.

Journal Article Am J Physiol Endocrinol Metab · February 2010 The anaplerotic odd-medium-chain triglyceride triheptanoin is used in clinical trials for the chronic dietary treatment of patients with long-chain fatty acid oxidation disorders. We previously showed (Kinman RP, Kasumov T, Jobbins KA, Thomas KR, Adams JE, ... Full text Link to item Cite

Catabolism of 4-hydroxyacids and 4-hydroxynonenal via 4-hydroxy-4-phosphoacyl-CoAs.

Journal Article J Biol Chem · November 27, 2009 4-Hydroxyacids are products of ubiquitously occurring lipid peroxidation (C(9), C(6)) or drugs of abuse (C(4), C(5)). We investigated the catabolism of these compounds using a combination of metabolomics and mass isotopomer analysis. Livers were perfused w ... Full text Link to item Cite

Interrelations between C4 ketogenesis, C5 ketogenesis, and anaplerosis in the perfused rat liver.

Journal Article J Biol Chem · October 9, 2009 We investigated the interrelations between C(4) ketogenesis (production of beta-hydroxybutyrate + acetoacetate), C(5) ketogenesis (production of beta-hydroxypentanoate + beta-ketopentanoate), and anaplerosis in isolated rat livers perfused with (13)C-label ... Full text Link to item Cite

Dynamics of glutathione and ophthalmate traced with 2H-enriched body water in rats and humans.

Journal Article Am J Physiol Endocrinol Metab · July 2009 We developed a LC-MS-MS assay of the (2)H labeling of free glutathione (GSH) and bound glutathione [GSSR; which includes all DTT-reducible forms, primarily glutathione disulfide (GSSG) and mixed disulfides with proteins] and ophthalmate (an index of GSH de ... Full text Link to item Cite

Folate fortification of rice by metabolic engineering.

Journal Article Nat Biotechnol · November 2007 Rice, the world's major staple crop, is a poor source of essential micronutrients, including folates (vitamin B9). We report folate biofortification of rice seeds achieved by overexpressing two Arabidopsis thaliana genes of the pterin and para-aminobenzoat ... Full text Link to item Cite

Regulation of one-carbon metabolism in Arabidopsis: the N-terminal regulatory domain of cystathionine gamma-synthase is cleaved in response to folate starvation.

Journal Article Plant Physiol · October 2007 In all organisms, control of folate homeostasis is of vital importance to sustain the demand for one-carbon (C1) units that are essential in major metabolic pathways. In this study we induced folate deficiency in Arabidopsis (Arabidopsis thaliana) cells by ... Full text Link to item Cite

Cytosolic hydroxymethyldihydropterin pyrophosphokinase/dihydropteroate synthase from Arabidopsis thaliana: a specific role in early development and stress response.

Journal Article J Biol Chem · April 6, 2007 In plants, 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase/7,8-dihydropteroate synthase (mitHPPK/DHPS) is a bifunctional mitochondrial enzyme, which catalyzes the first two consecutive steps of tetrahydrofolate biosynthesis. Mining the Arabidopsis geno ... Full text Link to item Cite

pH stability of individual folates during critical sample preparation steps in prevision of the analysis of plant folates.

Journal Article Phytochem Anal · 2007 The stability and eventual interconversion of nine mono-glutamate folates (5-methyl-tetrahydrofolate, tetrahydrofolate, 5-formyltetrahydrofolate, 5,10-methenyltetrahydrofolate, 5,10-methylenetetrahydrofolate, dihydrofolate, 10-formylfolic acid, 10-formylte ... Full text Link to item Cite

Investigation of the extraction behavior of the main monoglutamate folates from spinach by liquid chromatography-electrospray ionization tandem mass spectrometry.

Journal Article J Chromatogr A · June 17, 2005 An LC-MS/MS method has been developed for the determination of main monoglutamate folates in spinach with folic acid as an internal standard. A sample preparation with ultrafiltration (molecular weight cut-off membrane, 5 kDa) was followed by a chromatogra ... Full text Link to item Cite

Folate enhancement in staple crops by metabolic engineering

Journal Article Trends in Food Science and Technology · January 1, 2005 Folate deficiency has profound effects on human health and affects large population groups around the world. Plants are the main source of dietary folate, therefore, the creation of genetically modified crops with higher folate content may contribute to so ... Full text Cite

Free and total para-aminobenzoic acid analysis in plants with high-performance liquid chromatography/tandem mass spectrometry.

Journal Article Rapid Commun Mass Spectrom · 2005 para-Aminobenzoic acid (PABA), a precursor in the synthesis of folates in plants, is determined by liquid chromatography/tandem mass spectrometry (LC/MS/MS). In plants PABA can be converted into its beta-D-glucopyranosyl ester (PABA-Glc) and can also exist ... Full text Link to item Cite

Quantitative analysis of twelve sulfonamides in honey after acidic hydrolysis by high-performance liquid chromatography with post-column derivatization and fluorescence detection.

Journal Article J Chromatogr A · August 20, 2004 A quantitative HPLC-fluorescence method for the simultaneous determination of 12 sulfonamides (sulfaguanidine, sulfanilamide, sulfacetamide, sulfadiazine, sulfathiazole, sulfapyridine, sulfamerazine, sulfamether, sulfamethazine, sulfamethoxypyridazine, sul ... Full text Link to item Cite

Enhanced method performance due to a shorter chromatographic run-time in a liquid chromatography-tandem mass spectrometry assay for paclitaxel.

Journal Article J Chromatogr A · July 2, 2004 Liquid chromatography-tandem mass spectrometry (LC-MS-MS) is often performed in a high-throughput environment. Unfortunately, with atmospheric pressure ionization (API) techniques, shorter run-times or reduced sample clean-up often result in ion or matrix ... Full text Link to item Cite

Adduct formation in quantitative bioanalysis: effect of ionization conditions on paclitaxel.

Journal Article J Am Soc Mass Spectrom · April 2004 Quantitative analysis of target compounds with liquid chromatography atmospheric pressure ionization mass spectrometry is sometimes hampered by adduct formation. In these situations, cationization with alkali metal ions instead of proton addition is often ... Full text Link to item Cite

Determination of total folate in plant material by chemical conversion into para-aminobenzoic acid followed by high performance liquid chromatography combined with on-line postcolumn derivatization and fluorescence detection.

Journal Article J Agric Food Chem · December 31, 2003 A procedure involving chemical conversion of all forms of folate present in plant material into para-aminobenzoic acid (PABA) and a liquid chromatographic-fluorimetric determination with on-line postcolumn derivatization is reported. All folates are cleave ... Full text Link to item Cite

Development of integrated chemiluminescence flow sensor for the determination of adrenaline and isoprenaline

Journal Article Analytica Chimica Acta · July 22, 2002 A novel integrated chemiluminescence (CL) flow sensor for the determination of adrenaline and isoprenaline is developed based on the enhancing effect of analytes on CL emission of luminol oxidized by periodate in alkaline solution. The analytical reagents ... Full text Cite

Studies of polyluminol modified electrode and its application in electrochemiluminescence analysis with flow system

Journal Article Analytica Chimica Acta · August 15, 2000 In this work the electrochemical behavior of luminol in acidic solution is studied for the first time, and it is seen that luminol oxidized by electrochemistry can form the polymer on the surface of electrode, which is characterized by cyclic voltammetry ( ... Full text Cite

Studies of micelle and trace non-polar organic solvent on a new chemiluminescence system and its application to flow injection analysis

Journal Article Analytica Chimica Acta · March 23, 2000 A sensitive and stable IO4--H2O2 chemiluminescence (CL) system for flow injection determination of sodium dodecylbenzene sulfonate (SDBS) is described. Weak CL is emitted when H2O2 is oxidized by sodium periodate. In this system, various surfactants enhanc ... Full text Cite

Studies of the New Chemiluminescence System-NaIO4-H2O2-Trace Cyclohexane-Polyhydrophenols and Its Application

Journal Article Kao Teng Hsueh Hsiao Hua Heush Hsueh Pao/ Chemical Journal of Chinese Universities · January 10, 2000 The chemiluminescence (CL) generated from the hydrogen peroxide oxided by periodate could be enhanced differently by polyhydrophenols, such as pyrogallol, phloroglucinol, pyrocatechol, resorcinol and parodioxybenzene. Furthermore, the CL could be improved ... Cite

A sensitive photoinduced chemiluminescence method for the determination of riboflavin with flow injection analysis

Journal Article Analytical Letters · January 1, 2000 A sensitive chemiluminescence (CL) induced by light for the determination of riboflavin with flow injection analysis is developed. Riboflavin shows a strong enhancement effect on the CL reaction of luminol oxidized by periodate after the photochemical reac ... Full text Cite

Chemiluminescence studies of the oxidation of ascorbic acid with copper(II) catalyzed by halide anions and its application to the determination of halide anions and ascorbic acid

Journal Article Analytical Sciences · January 1, 2000 The oxidation reaction of ascorbic acid by copper(II) has been studied by chemiluminescence system of luminol/copper(II) in alkaline solution. Oxygen and halide anions (Cl, Br and I-) can greatly catalyze the oxidation of ascorbic acid, which produces acti ... Full text Cite

FIA determination of pyruvate in serum based on direct chemiluminescence oxidation

Journal Article Fresenius' Journal of Analytical Chemistry · January 1, 1999 Chemiluminescence was observed by mixing acidic potassium permanganate solution with pyruvate in the presence of quinine. A new simplified method for pyruvate determination based on this phenomenon was established. The chemiluminescence intensity is a line ... Full text Cite

Chemiluminescence method for cinchona alkaloids

Journal Article Analytical Letters · January 1, 1998 Chemiluminescence (CL) was achieved by oxidation of sulphide with cerium(IV) in the presence of cinchona alkaloids (quinine, quinidine or cinchonine). The CL intensity was correlated with the concentration of each cinchona alkaloid. Based on this phenomeno ... Full text Cite

Synthesis of 2-[2-(5-methylbenzothiazolyl)azo]-5-dimethylaminobenzoic acid and its application to the spectrophotometric determination of nickel

Conference Analyst · January 1, 1998 A new thiazolylazo reagent, 2-[2-(5-methylbenzothiazolyl)azo] -5-dimethylaminobenzoic acid (5-Me-BTAMB) was synthesized. Its chromogenic reaction with microamounts of nickel was studied in detail, and the stability constants of the complexes of Ni2+, Co2+, ... Full text Cite