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Hum Mutat 2019 Mar 14. Epub 2019 Mar 14.

Department of Pediatrics, Klinikum Reutlingen, Reutlingen, Germany.

Pyruvate carboxylase deficiency (PCD) is caused by bi-allelic mutations of the PC gene. The reported clinical spectrum includes a neonatal form with early death (type B), an infantile fatal form (type A), and an late onset form with isolated mild intellectual delay (type C). Apart from homozygous stop-codon mutations leading to type B PCD, a genotype-phenotype correlation has not otherwise been discernible. Read More

Biochim Biophys Acta Mol Cell Biol Lipids 2019 May 5;1864(5):654-661. Epub 2019 Feb 5.

Department of Biological Sciences, Wayne State University, Detroit, MI 48202, United States of America. Electronic address:

Previous studies have shown that the cardiolipin (CL)-deficient yeast mutant, crd1Δ, has decreased levels of acetyl-CoA and decreased activities of the TCA cycle enzymes aconitase and succinate dehydrogenase. These biochemical phenotypes are expected to lead to defective TCA cycle function. In this study, we report that signaling and anaplerotic metabolic pathways that supplement defects in the TCA cycle are essential in crd1Δ mutant cells. Read More

Biochem Biophys Res Commun 2019 Jan 22;508(1):87-91. Epub 2018 Nov 22.

Department of Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. Electronic address:

Stearoyl-CoA desaturase 1 (SCD1), a lipogenic enzyme that adds a double bond at the delta 9 position of stearate (C18: 0) and palmitate (C16: 0), has been proven to be important in the development of obesity. Mice with skin-specific deficiency of SCD1 (SKO) display increased whole-body energy expenditure, which is protective against adiposity from a high-fat diet because it improves glucose clearance, insulin sensitivity, and hepatic steatosis. Of note, these mice also display elevated levels of the "pro-inflammatory" plasma interleukin-6 (IL-6). Read More

Molecules 2018 Sep 13;23(9). Epub 2018 Sep 13.

Department of Human Nutrition, Foods and Exercise, College of Agricultural and Life Sciences, Virginia Tech, Blacksburg, VA 24060, USA.

In diabetes mellitus, the excessive rate of glucose production from the liver is considered a primary contributor for the development of hyperglycemia, in particular, fasting hyperglycemia. In this study, we investigated whether kaempferol, a flavonol present in several medicinal herbs and foods, can be used to ameliorate diabetes in an animal model of insulin deficiency and further explored the mechanism underlying the anti-diabetic effect of this flavonol. We demonstrate that oral administration of kaempferol (50 mg/kg/day) to streptozotocin-induced diabetic mice significantly improved hyperglycemia and reduced the incidence of overt diabetes from 100% to 77. Read More

Neuropediatrics 2018 Dec 25;49(6):369-372. Epub 2018 Jul 25.

Division of Biochemical Diseases, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

Pyruvate carboxylase (PC) is a biotin-containing enzyme that is responsible for the adenosine triphosphate-dependent carboxylation of pyruvate to oxaloacetate, a key intermediate in the tricarboxylic acid cycle. PC deficiency (OMIM 266150) is a rare autosomal recessive metabolic disease, causing elevation of pyruvate, lactate, and alanine. Three types of PC deficiency have been described in the literature; A, B, and C. Read More

Prenat Diagn 2018 May 12. Epub 2018 May 12.

Service de Gynécologie Obstetrique, Hopital Louis-Mourier, Colombes, France.

Objective: Pyruvate dehydrogenase deficiency (PDHD) and pyruvate carboxylase deficiency (PCD) are diseases with severe neonatal forms, and their low prevalence makes them difficult to diagnose during pregnancy. Our objective was to describe prenatal ultrasound features that may be suggestive of these diagnoses.

Methods: We analyzed 3 cases from our institution and reviewed 12 published cases of PDHD and 6 cases of PCD, recording all of the ultrasound signs, as well as magnetic resonance findings when available. Read More

AoB Plants 2017 Nov 17;9(6):plx064. Epub 2017 Nov 17.

Institute of Plant Molecular Biology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.

Aluminium (Al) toxicity is one of the most important limiting factors for crop yield in acidic soils. However, the mechanisms that confer Al tolerance still remain largely unknown. To understand the molecular mechanism that confers different tolerance to Al, we performed global transcriptome analysis to the roots and leaves of two contrasting soybean genotypes, BX10 (Al-tolerant) and BD2 (Al-sensitive) under 0 and 50 μM Al treatments, respectively. Read More

Front Biosci (Landmark Ed) 2018 03 1;23:1655-1679. Epub 2018 Mar 1.

Department of Molecular Pharmacology, Albert Einstein College of Medicine; 1300 Morris Park Ave, Bronx, NY 11354.

Manganese (Mn) is an essential nutrient for intracellular activities; it functions as a cofactor for a variety of enzymes, including arginase, glutamine synthetase (GS), pyruvate carboxylase and Mn superoxide dismutase (Mn-SOD). Through these metalloproteins, Mn plays critically important roles in development, digestion, reproduction, antioxidant defense, energy production, immune response and regulation of neuronal activities. Mn deficiency is rare. Read More

J Basic Microbiol 2018 Feb 5;58(2):187-197. Epub 2017 Dec 5.

Laboratory of Microbial Genetics, Department of Botany, Banaras Hindu University, Varanasi, India.

P protein family is widespread in prokaryotes and plants. In this study, impacts of P deficiency on the synthesis of acetyl CoA and acetyl CoA carboxylase enzyme (ACCase) was analyzed in the Synechococcus sp. PCC 7942 by evaluating the mRNA levels of pyruvate kinase (PK), pyruvate dehydrogenase (PDH), citrate synthase (CS), biotin synthase (BS), biotin carboxylase (BC), biotin carboxyl carrier protein (BCCP), carboxyl transferase (CT) α and β subunits. Read More

Oncotarget 2017 Sep 1;8(43):73627-73639. Epub 2017 Sep 1.

Department of Neurosurgery, Mackay Memorial Hospital, Taipei, Taiwan.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is most commonly caused by the A3243G mutation of mitochondrial DNA. The capacity to utilize fatty acid or glucose as a fuel source and how such dynamic switches of metabolic fuel preferences and transcriptional modulation of adaptive mechanism in response to energy deficiency in MELAS syndrome have not been fully elucidated. The fibroblasts from patients with MELAS syndrome demonstrated a remarkable deficiency of electron transport chain complexes I and IV, an impaired cellular biogenesis under glucose deprivation, and a decreased ATP synthesis. Read More

Cell Metab 2017 Dec 5;26(6):817-829.e6. Epub 2017 Oct 5.

Cancer Metabolism and Signaling Networks Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address:

Tumors undergo nutrient stress and need to reprogram their metabolism to survive. The stroma may play a critical role in this process by providing nutrients to support the epithelial compartment of the tumor. Here we show that p62 deficiency in stromal fibroblasts promotes resistance to glutamine deprivation by the direct control of ATF4 stability through its p62-mediated polyubiquitination. Read More

Indian J Pediatr 2017 12 23;84(12):959-960. Epub 2017 Aug 23.

Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India.

J Neurosci Res 2017 11 8;95(11):2236-2243. Epub 2017 Jul 8.

Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.

Triheptanoin is an odd-chain triglyceride with anaplerotic properties-that is, replenishing the pool of metabolic intermediates in the Krebs cycle. Unlike even-chain fatty acids metabolized to acetyl-CoA only, triheptanoin can indeed provide both acetyl-CoA and propionyl-CoA, two key carbon sources for the Krebs cycle. Triheptanoin was initially used in patients with long-chain fatty acid oxidation disorders. Read More

FASEB J 2017 09 1;31(9):4078-4087. Epub 2017 Jun 1.

Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.

Taurine (Tau) restores β-cell function in obesity; however, its action is lost in malnourished obese rodents. Here, we investigated the mechanisms involved in the lack of effects of Tau in this model. C57BL/6 mice were fed a control diet (CD) (14% protein) or a protein-restricted diet (RD) (6% protein) for 6 wk. Read More

J Biol Chem 2017 06 8;292(25):10455-10464. Epub 2017 May 8.

From the Departments of Biochemistry and Molecular Biology and

Disruption of the gene encoding the liver isoform of glycogen synthase generates a mouse strain (LGSKO) that almost completely lacks hepatic glycogen, has impaired glucose disposal, and is pre-disposed to entering the fasted state. This study investigated how the lack of liver glycogen increases fat accumulation and the development of liver insulin resistance. Insulin signaling in LGSKO mice was reduced in liver, but not muscle, suggesting an organ-specific defect. Read More

J Proteomics 2017 05 18;160:1-7. Epub 2017 Mar 18.

Department of Plant Biochemistry, Ruhr-University Bochum, 44801 Bochum, Germany; School of Biomedical and Healthcare Sciences, Plymouth University, Plymouth PL4 8AA, United Kingdom. Electronic address:

The metabolic status of individual cells in microbial cultures can differ, being relevant for biotechnology, environmental and medical microbiology. However, it is hardly understood in molecular detail due to limitations of current analytical tools. Here, we demonstrate that FACS in combination with proteomics can be used to sort and analyze cell populations based on their metabolic state. Read More

Nutrients 2017 Feb 22;9(2). Epub 2017 Feb 22.

Department of Diabetes and Endocrinology, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan.

Many articles have discussed the relationship between fructose consumption and the incidence of obesity and related diseases. Fructose is absorbed in the intestine and metabolized in the liver to glucose, lactate, glycogen, and, to a lesser extent, lipids. Unabsorbed fructose causes bacterial fermentation, resulting in irritable bowl syndrome. Read More

Biotechnol Prog 2017 May 11;33(3):749-758. Epub 2017 Mar 11.

Chemical Engineering and Process Development Div., CSIR-National Chemical Laboratory, Pune, 411008, India.

Inorganic phosphate (P ) is an essential ion involved in diverse cellular processes including metabolism. Changes in cellular metabolism upon long term adaptation to P limitation have been reported in E. coli. Read More

Adv Biochem Eng Biotechnol 2017;159:181-198

Laboratory of Microbial Physiology, Research Faculty of Agriculture, Hokkaido University, Kita-9 Nishi-9, Kita-ku, Sapporo, 060-8589, Japan.

In the 1980s, Shiio and coworkers demonstrated using random mutagenesis that the following three phenotypes were effective for boosting lysine production by Corynebacterium glutamicum: (1) low-activity-level citrate synthase (CS), (2) phosphoenolpyruvate carboxylase (PEPC) resistant to feedback inhibition by aspartic acid (PEPC), and (3) pyruvate kinase (PYK) deficiency. Here, we reevaluated these phenotypes and their interrelationship in lysine production using recombinant DNA techniques.The pyk deletion and PEPC (D299N in ppc) independently showed marginal effects on lysine production, but both phenotypes synergistically increased lysine yield, demonstrating the importance of PEPC as an anaplerotic enzyme in lysine production. Read More

Metab Eng 2017 09 14;43(Pt B):198-207. Epub 2016 Nov 14.

Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA; Department of Pediatrics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA; McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA. Electronic address:

The mitochondrial citrate transport protein (CTP), encoded by SLC25A1, accommodates bidirectional trafficking of citrate between the mitochondria and cytosol, supporting lipid biosynthesis and redox homeostasis. Genetic CTP deficiency causes a fatal neurodevelopmental syndrome associated with the accumulation of L- and D-2-hydroxyglutaric acid, and elevated CTP expression is associated with poor prognosis in several types of cancer, emphasizing the importance of this transporter in multiple human pathologies. Here we describe the metabolic consequences of CTP deficiency in cancer cells. Read More

Adv Exp Med Biol 2016 ;949:227-243

Neurodegeneration Laboratory, Institut Pasteur Montevideo, Montevideo, Uruguay.

Astrocytes play crucial roles in maintaining brain homeostasis and in orchestrating neural development, all through tightly coordinated steps that cooperate to maintain the balance needed for normal development. Here, we review the alterations in astrocyte functions that contribute to a variety of developmental neurometabolic disorders and provide additional data on the predominant role of astrocyte dysfunction in the neurometabolic neurodegenerative disease glutaric acidemia type I. Finally, we describe some of the therapeutical approaches directed to neurometabolic diseases and discuss if astrocytes can be possible therapeutic targets for treating these disorders. Read More

J Nutr Sci Vitaminol (Tokyo) 2016 ;62(2):81-7

Department of Dietary Environment Analysis, School of Human Science and Environment, University of Hyogo.

Biotin is a water-soluble vitamin that functions as a cofactor for biotin-dependent carboxylases. The biochemical and physiological roles of biotin in brain regions have not yet been investigated sufficiently in vivo. Thus, in order to clarify the function of biotin in the brain, we herein examined biotin contents, biotinylated protein expression (e. Read More

J Inherit Metab Dis 2016 09 22;39(5):597-610. Epub 2016 Apr 22.

Department of Department of Biochemistry, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, 59 bd Pinel, 69677, Bron cedex, France.

This review highlights the importance of performing an autopsy when faced with fetal abortion or termination of pregnancy with suspicion of an inborn error of metabolism. Radiological, macroscopic and microscopic features found at autopsy as well as placental anomalies that can suggest such a diagnosis are detailed. The following metabolic disorders encountered in fetuses are discussed: lysosomal storage diseases, peroxisomal disorders, cholesterol synthesis disorders, congenital disorders of glycosylation, glycogenosis type IV, mitochondrial respiratory chain disorders, transaldolase deficiency, generalized arterial calcification of infancy, hypophosphatasia, arylsulfatase E deficiency, inborn errors of serine metabolism, asparagine synthetase deficiency, hyperphenylalaninemia, glutaric aciduria type I, non-ketotic hyperglycinemia, pyruvate dehydrogenase deficiency, pyruvate carboxylase deficiency, glutamine synthase deficiency, sulfite oxidase and molybdenum cofactor deficiency. Read More

Am J Physiol Heart Circ Physiol 2016 06 15;310(11):H1520-32. Epub 2016 Apr 15.

Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama;

Circadian clocks are critical modulators of metabolism. However, mechanistic links between cell autonomous clocks and metabolic processes remain largely unknown. Here, we report that expression of the biotin transporter slc5a6 gene is decreased in hearts of two distinct genetic mouse models of cardiomyocyte-specific circadian clock disruption [i. Read More

Diabetes 2016 06 18;65(6):1521-33. Epub 2016 Mar 18.

Department of Internal Medicine, University of Utah, Salt Lake City, UT Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC Department of Biochemistry, University of Utah, Salt Lake City, UT

Hypoxia and iron both regulate metabolism through multiple mechanisms, including hypoxia-inducible transcription factors. The hypoxic effects on glucose disposal and glycolysis are well established, but less is known about the effects of hypoxia and iron deficiency on hepatic gluconeogenesis. We therefore assessed their effects on hepatic glucose production in mice. Read More

J Biosci Bioeng 2016 Aug 13;122(2):160-7. Epub 2016 Mar 13.

Laboratory of Microbial Physiology, Research Faculty of Agriculture, Hokkaido University, Kita-9 Nishi-9, Kita-ku, Sapporo, Hokkaido 060-8589, Japan. Electronic address:

Various attempts have been made to enhance lysine production in Corynebacterium glutamicum. Pyruvate kinase (PYK) defect is one of the strategies used to enhance the supply of oxaloacetic acid (OAA), a precursor metabolite for lysine biosynthesis. However, inconsistent effects of this mutation have been reported: positive effects of PYK defect in mutants having phosphoenolpyruvate carboxylase (PEPC) desensitized to feedback inhibition by aspartic acid, while negative effects in simple PYK gene (pyk) knockout mutants. Read More

Mol Genet Metab 2015 Nov 1;116(3):204-14. Epub 2015 Sep 1.

Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas de la Universidad Nacional Autónoma de México y del Instituto Nacional de Pediatría, México D.F., México. Electronic address:

Certain inborn errors of metabolism result from deficiencies in biotin containing enzymes. These disorders are mimicked by dietary absence or insufficiency of biotin, ATP deficit being a major effect,whose responsible mechanisms have not been thoroughly studied. Here we show that in rats and cultured cells it is the result of reduced TCA cycle flow, partly due to deficient anaplerotic biotin-dependent pyruvate carboxylase. Read More

Antioxid Redox Signal 2015 Oct 24;23(10):761-74. Epub 2015 Aug 24.

Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa , Honolulu, Hawaii.

Aims: Selenocysteine lyase (Scly) mediates selenocysteine decomposition. It was previously demonstrated that, upon adequate caloric intake (12% kcal fat) and selenium deficiency, disruption of Scly in mice leads to development of metabolic syndrome. In this study, we investigate the effect of a high-fat (45% kcal) selenium-adequate diet in Scly knockout (KO) mice on development of metabolic syndrome. Read More

J Biosci Bioeng 2016 Feb 11;121(2):172-7. Epub 2015 Jul 11.

Laboratory of Microbial Physiology, Research Faculty of Agriculture, Hokkaido University, Kita-9 Nishi-9, Kita-ku, Sapporo, Hokkaido 060-8589, Japan. Electronic address:

Phosphoenolpyruvate carboxylase (PEPC) in Corynebacterium glutamicum ATCC13032, a glutamic-acid producing actinobacterium, is subject to feedback inhibition by metabolic intermediates such as aspartic acid and 2-oxoglutaric acid, which implies the importance of PEPC in replenishing oxaloacetic acid into the TCA cycle. Here, we investigated the effects of feedback-insensitive PEPC on glutamic acid production. A single amino-acid substitution in PEPC, D299N, was found to relieve the feedback control by aspartic acid, but not by 2-oxoglutaric acid. Read More

Immunology 2015 Oct 27;146(2):292-300. Epub 2015 Jul 27.

Department of Nephrology, Medical School, University of Thessaly, Larissa, Greece.

Indoleamine 2,3-dioxygenase (IDO) is expressed in antigen-presenting cells and exerts immunosuppressive effects on CD4(+) T cells. One mechanism is through the inhibition of aerobic glycolysis. Another prerequisite for T-cell proliferation and differentiation into effector cells is increased fatty acid (FA) synthesis. Read More

Mol Genet Metab Rep 2015 Mar 28;2:25-31. Epub 2014 Nov 28.

Centre de Référence des Maladies Héréditaires du Métabolisme, Hôpital Necker, APHP, Paris, France.

Pyruvate carboxylase (PC) is a biotin-containing mitochondrial enzyme that catalyzes the conversion of pyruvate to oxaloacetate, thereby being involved in gluconeogenesis and in energy production through replenishment of the tricarboxylic acid (TCA) cycle with oxaloacetate. PC deficiency is a very rare metabolic disorder. We report on a new patient affected by the moderate form (the American type A). Read More

FEBS Lett 2014 Nov 19;588(21):3947-53. Epub 2014 Sep 19.

Department of Biological Sciences, College of Natural Sciences, Chonnam National University, South Korea. Electronic address:

We show that testicular orphan nuclear receptor 4 (TR4) increases the expression of pyruvate carboxylase (PC) gene in 3T3-L1 adipocytes by direct binding to a TR4 responsive element in the murine PC promoter. While TR4 overexpression increased PC activity, oxaloacetate (OAA) and glycerol levels with enhanced incorporation of (14)C from (14)C-pyruvate into fatty acids in 3T3-L1 adipocytes, PC knockdown by short interfering RNA (siRNA) or inhibition of PC activity by phenylacetic acid (PAA) abolished TR4-enhanced fatty acid synthesis. Moreover, TR4 microRNA reduced PC expression with decreased fatty acid synthesis in 3T3-L1 adipocytes, suggesting that TR4-mediated enhancement of fatty acid synthesis in adipocytes requires increased expression of PC gene. Read More

Tree Physiol 2014 Jun 23;34(6):608-18. Epub 2014 Jun 23.

College of Resource and Environmental Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China Institute of Horticultural Plant Physiology, Biochemistry and Molecular Biology, Fujian Agriculture and Forestry University, Fuzhou 350002, China Fujian Key Laboratory for Plant Molecular and Cell Biology, Fujian Agriculture and Forestry University, Fuzhou 350002, China

Boron (B) deficiency is a widespread problem in many crops, including Citrus. The effects of B-deficiency on gas exchange, carbohydrates, organic acids, amino acids, total soluble proteins and phenolics, and the activities of key enzymes involved in organic acid and amino acid metabolism in 'Xuegan' [Citrus sinensis (L.) Osbeck] leaves and roots were investigated. Read More

Endocrinology 2014 Aug 10;155(8):2881-91. Epub 2014 Jun 10.

Laboratório de Bioenergética (M.N., A.T.S., C.S.B., L.A.K., L.d.M.), Instituto de Bioquímica Médica, Laboratório de Radiobiologia Molecular (R.S.F.) and Laboratório de Fisiologia Endócrina Doris Rosenthal (R.A.N.L., D.P.C.), Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.

Menopause is associated with increased visceral adiposity and disrupted glucose homeostasis, but the underlying molecular mechanisms related to these metabolic changes are still elusive. Brown adipose tissue (BAT) plays a key role in energy expenditure that may be regulated by sexual steroids, and alterations in glucose homeostasis could precede increased weight gain after ovariectomy. Thus, the aim of this work was to evaluate the metabolic pathways in both the BAT and the liver that may be disrupted early after ovariectomy. Read More

J Exp Bot 2014 Jul 10;65(12):2995-3003. Epub 2014 Apr 10.

Department of Plant Nutrition, China Agricultural University, Beijing 100193, P. R. China.

Light intensity affects photosynthetic carbon (C) fixation and the supply of carbon to roots. To evaluate interactions between carbon supply and phosphorus (P) supply, effects of light intensity on sucrose accumulation, root growth, cluster root formation, carboxylate exudation, and P uptake capacity were studied in white lupin (Lupinus albus L.) grown hydroponically with either 200 µmol m(-2) s(-1) or 600 µmol m(-2) s(-1) light and a sufficient (50 µM P) or deficient (1 µM P) P supply. Read More

Oncogene 2015 Feb 17;34(8):1044-50. Epub 2014 Mar 17.

Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.

Cancer cells are reprogrammed to utilize glycolysis at high rates, which provides metabolic precursors for cell growth. Consequently, glucose levels may decrease substantially in underperfused tumor areas. Gluconeogenesis results in the generation of glucose from smaller carbon substrates such as lactate and amino acids. Read More

Am J Hum Genet 2014 Mar 13;94(3):453-61. Epub 2014 Feb 13.

Division of Biochemical Diseases, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3V4, Canada; Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3V4, Canada; Treatable Intellectual Disability Endeavour in British Columbia, BC Children's Hospital, University of British Columbia, Vancouver, BC V5Z 4H4, Canada.

Four children in three unrelated families (one consanguineous) presented with lethargy, hyperlactatemia, and hyperammonemia of unexplained origin during the neonatal period and early childhood. We identified and validated three different CA5A alterations, including a homozygous missense mutation (c.697T>C) in two siblings, a homozygous splice site mutation (c. Read More

Adv Clin Chem 2014 4;67:73-150. Epub 2014 Nov 4.

Department of Clinical Biochemistry, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom. Electronic address:

Human adults produce around 1000 mmol of ammonia daily. Some is reutilized in biosynthesis. The remainder is waste and neurotoxic. Read More

Int J Obes (Lond) 2014 Sep 16;38(9):1172-9. Epub 2013 Dec 16.

1] Department of Life Sciences, Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan [2] Rong Hsing Research Center for Translational Medicine and the iEGG Center, National Chung Hsing University, Taichung, Taiwan.

Objective: Fatty liver disease is commonly associated with obesity, insulin resistance and diabetes. Severe fatty liver is sometimes accompanied by steatohepatitis and may lead to the development of hepatocellular carcinoma. At present, there is no effective treatment for non-alcoholic fatty liver disease (NAFLD); thus, recent investigations have focused on developing effective therapeutics to treat this condition. Read More

Eur J Pediatr 2014 Mar 10;173(3):361-6. Epub 2013 Oct 10.

Willink Unit, Genetic Medicine, Manchester Academic Health Sciences Centre, Central Manchester University Hospitals NHS Foundation Trust, Oxford Road, Manchester, M13 9WL, UK.

Unlabelled: Pyruvate carboxylase (PC) deficiency (OMIM 266150) is an autosomal recessive disorder that usually presents with lactic acidaemia and severe neurological dysfunction, leading to death in infancy. Because the enzyme is involved in gluconeogenesis and anaplerosis of the Krebs cycle, therapeutic strategies have included avoiding fasting and attempts to correct the defect of anaplerosis. Triheptanoin is a triglyceride of C7 fatty acids. Read More

An Pediatr (Barc) 2014 Mar 5;80(3):184-6. Epub 2013 Oct 5.

Unidad de Nutrición y Metabolopatías, Hospital La Fe, Valencia, España.

We report a case of holocarboxylase synthetase deficiency with normal pyruvate carboxylase activity in the lymphocytes of an 8 year-old girl with clinical toxicity without the classic dermatological involvement. The identification of three nucleotide changes in the holocarboxylase synthetase (HLCS) gene, only one of them described as a pathogenic mutation could be related to a slight variant of the disease that would explain the unusual presentation beyond the age of infant. Treatment with biotin at 40 mg/day with protein controlled diet allows normal physical growth and psychomotor development for their age. Read More

Metabolism 2013 Nov 27;62(11):1673-85. Epub 2013 Aug 27.

Department of Molecular Physiology and Biophysics; Department of Internal Medicine/Division of Diabetes, Endocrinology, and Metabolism; Department of Cellular and Integrative Physiology, University of Nebraska Medical Center; VA Nebraska Western Iowa Health Care System, Omaha, NE. Electronic address:

Objective: Adipose tissue (AT)-specific inflammation is considered to mediate the pathological consequences of obesity and macrophages are known to activate inflammatory pathways in obese AT. Because cyclooxygenases play a central role in regulating the inflammatory processes, we sought to determine the role of hematopoietic cyclooxygenase-1 (COX-1) in modulating AT inflammation in obesity.

Materials/methods: Bone marrow transplantation was performed to delete COX-1 in hematopoietic cells. Read More

Gene 2013 Dec 23;532(2):302-6. Epub 2013 Aug 23.

Department of Neurology, Hospital Sant Joan de Déu, Barcelona, Spain; CIBERER (Biomedical Network Research Centre on Rare Diseases), Instituto de Salud Carlos III, Madrid, Spain.

Pyruvate carboxylase deficiency is a rare metabolic disorder, with three different phenotypes. We aim to report the case of a newborn presenting the severe neonatal form of this deficiency (the B or "French" phenotype, hypokinesia and rigidity being the main features) and the results of the study of classic neurotransmitters involved in movement control. Hyperdopaminergic transmission (both in the cerebrospinal fluid and in the substantia nigra) and hypoGABAergic transmission (in the substantia nigra) were found. Read More

Metabolism 2013 Nov 5;62(11):1651-61. Epub 2013 Aug 5.

Orentreich Foundation for the Advancement of Science, Inc., 855 Route 301, Cold Spring-on-Hudson, NY 10516, USA. Electronic address:

Objective: This study investigated the effects of dietary methionine restriction (MR) on the progression of established hepatic steatosis in the leptin-deficient ob/ob mouse.

Material/methods: Ten-week-old ob/ob mice were fed diets containing 0.86% (control-fed; CF) or 0. Read More

Mol Genet Metab 2013 Sep-Oct;110(1-2):145-52. Epub 2013 Jul 19.

Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.

Unlabelled: Diagnosing primary mitochondrial respiratory chain (RC) dysfunction has long relied on invasive tissue biopsies, since no blood-based biomarker has been shown to have sufficiently high sensitivity and specificity across the myriad of individual clinical presentations. We sought to determine whether cohort-level evaluation of commonly obtained blood analytes might reveal consistent patterns to discriminate a heterogenous group of primary mitochondrial RC disease subjects both from control individuals and from subjects with pyruvate dehydrogenase deficiency.

Methods: Following IRB approval, 62 biochemical analyte concentrations or ratios were retrospectively analyzed in three well-defined and intentionally heterogeneous subject cohorts reflective of clinical practice: [1] Primary mitochondrial disease (n=19); [2] pyruvate dehydrogenase deficiency (n=4); and [3] controls (n=27). Read More

Anesthesiology 2013 Nov;119(5):1120-36

* Research Associate, ‖ Visiting Professor, ** Professor, The Department of Anesthesia and Perioperative Care, † Professor, The Department of Epidemiology and Biostatistics, ‡ Research Associate Professor, # Professor, The Department of Pharmaceutical Chemistry, The University of California San Francisco, San Francisco, California. § NMR Spectroscopist and Laboratory Manager, QB3 Physical Biosciences Division, Lawrence Berkeley National Laboratory, The University of California, Berkeley, California.

Background: Mild brain hypothermia (32°-34°C) after human neonatal asphyxia improves neurodevelopmental outcomes. Astrocytes but not neurons have pyruvate carboxylase and an acetate uptake transporter. C nuclear magnetic resonance spectroscopy of rodent brain extracts after administering [1-C]glucose and [1,2-C]acetate can distinguish metabolic differences between glia and neurons, and tricarboxylic acid cycle entry via pyruvate dehydrogenase and pyruvate carboxylase. Read More

J Biol Chem 2013 Jul 20;288(27):19739-49. Epub 2013 May 20.

Department of Medicine, Washington University, St Louis, Missouri 63110, USA.

Preservation of bioenergetic homeostasis during the transition from the carbohydrate-laden fetal diet to the high fat, low carbohydrate neonatal diet requires inductions of hepatic fatty acid oxidation, gluconeogenesis, and ketogenesis. Mice with loss-of-function mutation in the extrahepatic mitochondrial enzyme CoA transferase (succinyl-CoA:3-oxoacid CoA transferase, SCOT, encoded by nuclear Oxct1) cannot terminally oxidize ketone bodies and develop lethal hyperketonemic hypoglycemia within 48 h of birth. Here we use this model to demonstrate that loss of ketone body oxidation, an exclusively extrahepatic process, disrupts hepatic intermediary metabolic homeostasis after high fat mother's milk is ingested. Read More

Endocr J 2013 10;60(8):941-50. Epub 2013 May 10.

Department of Endocrinology, Provincial Hospital Affiliated to Shandong University, Jinan, China.

Our previous study reported that thyroid-stimulating hormone (TSH) promotes cholesterol synthesis via the cyclic adenosine monophosphate/protein kinase A/cAMP regulatory element-binding protein (cAMP/PKA/CREB) pathway after binding to TSH receptors (TSHR) in the liver. The hepatic cAMP/PKA/CREB pathway also plays an important role in maintaining fasting glucose homeostasis. These findings implied a possible role for TSH in hepatic glucose metabolism. Read More

Handb Clin Neurol 2013 ;113:1667-73

Pediatric Neurology and Metabolism, Universitair Ziekenhuis Brussel, Brussels, Belgium. Electronic address:

Pyruvate dehydrogenase and pyruvate carboxylase deficiency are the most common disorders in pyruvate metabolism. Diagnosis is made by enzymatic and DNA analysis after basic biochemical tests in plasma, urine, and CSF. Pyruvate dehydrogenase has three main subunits, an additional E3-binding protein and two complex regulatory enzymes. Read More