case western reserve university

NUTRITION

 


            
            Janos Kerner, PhD

            Associate Professor

 

office:
SOM W165

lab:
SOM W161


phone:  (216) 368-5358
fax:  (216) 368-6644
email: janos.kerner@case.edu


mailing address:
Department of Nutrition
Case Western Reserve University
School of Medicine • WG 48
10900 Euclid Avenue
Cleveland OH 44106-4954

 

A little background

Janos Kerner graduated from Humboldt University in Berlin (Germany) where he received his M.S. in biology/plant biochemistry. He accepted a teaching/research position in the Department of Biochemistry at Medical University of Pecs (Hungary) where he received his Ph.D. in biochemistry. He held a faculty position at Medical University at Pecs until 1994. During his faculty appointment in the Department of Biochemistry at the Medical University of Pecs, he worked for several years as a visiting faculty in the Department of Biochemistry at Michigan State University. He joined the faculty in the Department of Nutrition at CWRU in 1995.

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RESEARCH INTERESTS

My research interest has been the elucidation of the functions of carnitine acyltransferases and acylcarnitines in intermediary metabolism and the investigation of the regulation of mitochondrial malonyl-CoA sensitive carnitine palmitoyltransferase (CPT-I).  

During my past research I was interested in method and assay developments for identification and quantitation of individual acylcarnitines.  Since then I have shown that carnitine is involved in specific detoxification reactions, and in modulating the acyl-CoA/CoASH ratio in cellular compartments. My current research is in the area of mitochondrial fatty acid oxidation with special emphasis on the malonyl-CoA sensitive carnitine palmitoyltransferase. CPT-I exists in two isoforms, the liver and muscle specific isoform, and catalyzes the rate controlling step of mitochondrial fatty acid oxidation.

Consequently, its regulation (allostericaly by malonyl-CoA and covalently by phosphorylation) is central to several pathological conditions. Our aim is to elucidate how the two isoforms are regulated in vivo under physiological and pathological conditions using a multifaceted approach which involves enzymological and immunological methods as well as proteomics.

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PUBLICATIONS

    Minkler PE, Kerner J, North KN, Hoppel CL.   Quantitation of long-chain acylcarnitines by HPLC/fluorescence detection: application to plasma and tissue specimens from patients with carnitine palmitoyltransferase-II deficiency.  Clin Chim Acta. 2005 Feb; 352(1-2):81-92.  PMID: 15653102 [PubMed - in process]

  • Steiber A, Kerner J, Hoppel CL.  Carnitine: a nutritional, biosynthetic, and functional perspective.  Mol Aspects Med. 2004 Oct-Dec; 25(5-6):455-73. PMID: 15363636 [PubMed - in process]

  • Kerner J, Distler AM, Minkler P, Parland W, Peterman SM, Hoppel CL.  Phosphorylation of rat liver mitochondrial carnitine palmitoyltransferase-I: effect on the kinetic properties of the enzyme.  J Biol Chem. 2004 Sep 24; 279(39):41104-13. Epub 2004 Jul 09. PMID: 15247243 [PubMed - indexed for MEDLINE]

  • Chandler MP, Kerner J, Huang H, Vazquez E, Reszko A, Martini WZ, Hoppel CL, Imai M, Rastogi S, Sabbah HN, Stanley WC.  Moderate severity heart failure does not involve a downregulation of myocardial fatty acid oxidation.  Am J Physiol Heart Circ Physiol. 2004 Oct; 287(4):H1538-43. Epub 2004 Jun 10. PMID: 15191896 [PubMed - indexed for MEDLINE]

  • Minkler PE, Anderson VE, Maiti NC, Kerner J, Hoppel CL.  Isolation and identification of two isomeric forms of malonyl-coenzyme A in commercial malonyl-coenzyme A.  Anal Biochem. 2004 May 15; 328(2):203-9.  PMID: 15113698 [PubMed - indexed for MEDLINE]

  • Sterk JP, Stanley WC, Hoppel CL, Kerner J.  A radiochemical pyruvate dehydrogenase assay: activity in heart.  Anal Biochem. 2003 Feb 1; 313(1):179-82. No abstract available.  PMID: 12576077 [PubMed - indexed for MEDLINE]

  • Kerner J and Hoppel CL.   Radiochemical malonyl-CoA decarboxylase assay: activity and subcellular distribution in heart and skeletal muscle.  Anal Biochem. 2002 Jul 15; 306(2):283-9. PMID: 12123667 [PubMed - indexed for MEDLINE]

  • Hoppel CL, Kerner J, Turkaly P, Minkler PE, and Tandler B.   Isolation of hepatic mitochondrial contact sites: previously unrecognized inner membrane components.  Anal.Biochem., 302:60-69, 2002.

  • Kerner J, Turkaly PJ, Minkler PE, and Hoppel CL.   Aging skeletal muscle mitochondria in the rat: decreased uncoupling protein-3 content.  Am.J.Physiol., 281:E1054-E1062, 2001.

  • Hoppel C, Kerner J, Turkaly P, and Tandler B.   Rat liver mitochondrial contact sites and carnitine palmitoyltransferase-I.  Arch.Biochem.Biophys. 392(2):321-325, 2001.

  • Lesnefsky EJ, Moghaddas S, Tandler B, Kerner J, and Hoppel CL. Mitochondrial dysfunction in cardiac disease: ischemia-reperfusion, aging, and heart failure.  J.Mol.Cell. Cardiol. 33(6), 1065-1089, 2001.

  • Kerner J and Hoppel C.   Fatty acid import into mitochondria. Biochim. Biophys. Acta 1486 :1-17, 2000.

  • Turkaly P, Kerner J, and Hoppel C.   A 22kDa polyanion inhibits carnitine-dependent fatty acid oxidation in rat liver mitochondria.  FEBS Letters,  460 :241-245, 1999.

  • Hoppel CL, Kerner J, Turkaly P, Turkaly J, and Tandler B.   The malonyl-CoA-sensitive form of carnitine palmitoyltransferase is not localized exclusively in the outer membrane of rat liver mitochondria.  J.Biol.Chem., 273 :23495-23503, 1998.

  • Kerner J, and Hoppel C.  Genetic disorders of carnitine metabolism and their nutritional management.  Ann. Rev. Nutr., 18: 179-206, 1998.

  • Panchal AR, Stanley WC, Kerner J, and Sabbah HN. Beta-receptor blockage decreases carnitine palmitoyltransferase I activity in dogs with heart failure.  J Card Fail. 1998 Jun; 4(2):121-6.
  • Kerner J, Huang ZH, and Chaudry IH.   Impaired gut lipid absorptive capacity after trauma-hemorrhage and resuscitation. Am J Physiol. 1995 Oct; 269(4 Pt 2):R869-73.
  • Kerner J and Bieber LL.   Conversion of carnitine palmitoyltransferase of rat heart mitochondria into a high affinity, malonyl-CoA inhibited state.  Biochem.Arch., 10:95-101, 1994.

  • Kerner J, Zaluzec E., Gage D., and Bieber L.L.   Characterization of the malonyl-CoA-sensitive carnitine palmitoyltransferase (CPTo) of a rat heart mitochondrial particle: Evidence that the catalytic unit is CPTi.  J.Biol.Chem., 269:8209-8219, 1994.

  • Zezza F, Kerner J, Pascale MR, Giannini R, and Arrigoni-Martelli E.   Rapid determination of amino acids by high-performance liquid chromatography: release of amino acids by perfused liver. J.Chrom., 593:99-101, 1992.

  • Lilly K., Chung C., Kerner J., VanRenterghem R., and Bieber L.L.   The effect of etomoxiryl-CoA on different carnitine acyltransferases.  Biochem.Pharmacol., 43:353-361, 1992.

  • DiLisa F., Bieber L.L., Kerner J., Menabo R., Barbato R., and Siliprandi N.   Methods for carnitine assay.  In: L-carnitine and its role in medicine: from function to therapy, 37-61, 1992. Eds.: Ferrari, R., DiMauro., and Sherwood, G., Academic Press.

  • Schmidt-Sommerfeld E., Penn D., Bieber L.L., Kerner J., Rossi T.M. and Lebenthal E.   Carnitine ester excretion in pediatric patients receiving parenteral nutrition.  Pediatr.Res., 28:158-165, 1990.

  • Melegh B., Kerner J., Acsadi Gy., Lakatos J., and Sandor A.   L-carnitine replacement therapy in chronic valproate treatment.  Neuropediatrics, 21:40-43, 1990.

  • Kerner J., and Bieber L.L.   Isolation of a malonyl-CoA sensitive CPT/ -oxidation enzyme complex from rat heart mitochondria.  Biochemistry, 29:4326-4334, 1990.

  • Melegh B, Kerner J, Jaszai V, and Bieber LL.   Differential excretion of xenobiotic acyl-esters of carnitine due to pivampicillin and valproate.  Biochem.Med.Metab.Biol., 43:30-38, 1990.

  • Schmidt-Sommerfeld E, Penn D, Kerner J, and Bieber LL.   Acylcarnitines in the urine of a patient with medium chain acyl-CoA dehydrogenase (MCAD) deficiency and in normal children. Prog Clin Biol Res. 1990;321:403-9. No abstract available. PMID: 2326301 [PubMed - indexed for MEDLINE]

  • Schmidt-Sommerfeld E, Penn D, Kerner J, Bieber LL, Rossi TM, and Lebenthal E.   Quantitation of urinary carnitine esters in a patient with medium-chain acyl-coenzyme A dehydrogenase deficiency: effect of metabolic state and L-carnitine therapy.  Pediatr., 115:577-582, 1989.

  • Schmidt-Sommerfeld E, Penn D, Kerner J, and Bieber LL.   Analysis of acylcarnitines in normal human urine with the radioisotopic exchange-high performance liquid chromatography (HPLC) method.  Clin.Chim. Acta, 181:231-238, 1989.

  • Healy MJ, Kerner J, and Bieber LL.   Enzymes of carnitine acylation. Is overt carnitine palmitoyltransferase of liver peroxisomal carnitine octanoyltransferase?  Biochem.J., 249:231-237, 1988.

  • Melegh B, Szucs L, Kerner J, and Sandor A.   Changes of plasma free amino acids and renal clearances of carnitines in premature infants during L-carnitine supplemented human milk feeding. J. Pediatr. Gastroenterol. Nutr., 7: 424-429, 1988.

  • Fiol CJ, Kerner J, and Bieber LL.   Effect of malonyl-CoA on the kinetics and substrate cooperativity of membrane-bound carnitine palmitoyltransferase of rat heart mitochondria. Biochem. Biophys. Acta, 916: 482-492, 1987.

  • Melegh B, Kerner J, and Bieber LL.   Pivampicillin-promoted excretion of pivaloylcarnitine in humans.  Biochem. Pharmacol., 36: 3405-3409, 1987.

  • Melegh B, Kerner J, Kispal Gy, Acsadi Gy, and Dani M.   Effect of chronic valproic treatment on plasma and urine carnitine levels in children: decreased urinary excretion.  Acta Paed. Hung., 28: 137-142, 1987.

  • Melegh B, Kerner J, Sandor A, Vinceller M, and Kispal Gy.   Effects of oral L-carnitine supplementation in low-birth-weight premature infants maintained on human milk. Biol.Neonate, 51: 185-193, 1987.

  • Romsos DR, Vander Tuig JG, Kerner J, and Grogan CK.   Energy balance in rats with obesity-producing hypothalamic knife cuts: effects of adrenalectomy.  J.Nutr., 117: 1121-1128, 1987.

  • Bieber LL and Kerner J.   Short-chain acylcarnitines: identification and quantification. Methods in Enzymology, 123: H264-276, 1986; Eds. Chytil, F., and McCormick, D.B., Academic Press.

  • Bieber LL, Lysiak W, and Kerner J.   Use of HPLC for assaying carnitine derivatives. Clinical aspects of human carnitine deficiency., Ed. Borum, P.R., Pergamon Press 1986, pp.66-74.

  • Melegh B, Kerner J, Sandor A, Vinceller M, and Kispal Gy.   Oral L-carnitine supplementation in low-birth-weight newborns: a study on neonates requiring combined parenteral and enteral nutrition.  Acta Paed. Hung., 27:253-258, 1986.

  • Melegh B, Kerner J, Vinceller M, and Kispal Gy.   Uptake of beta-hydroxybutyrate, acetoacetate and glucose by the forearm of the newborn infant.  Acta Paed. Hung., 27:323-327, 1986.

  • Vander Tuig JG, Kerner J, Crist KA, and Romsos DR.   Impaired thermoregulation in cold-exposed rats with hypothalamic obesity.  Metabolism, 35:960-966, 1986.

  • Vander Tuig JG, Kerner J, and Romsos DR.   Hypothalamic obesity, brown adipose tissue and sympathoadreansl activity in rats.  Amer.J.Physiol., 248:E607-E617, 1985.

  • Kerner J, and Bieber LL.   Isolation and identification of -methyloctanoylcarnitines from human urine.  Prep. Biochem., 15:237-257, 1985.

  • Valker K, Ely S, Kerner J, Scott J, and Bieber LL.   Effect of hypoxia on pig heart short-chain acylcarnitines.  Comp.Biochem.Physiol., 80:A123-127, 1985.

  • Kerner J, Froseth JA, Miller ER, and Bieber LL.   A study of the acylcarnitine content of sow's colostrum, milk and newborn piglet tissues: demonstration of high amounts of isovalerylcarnitine in colostrum and milk.  J.Nutr., 114:854-861, 1984.

  • Kerner J and Bieber LL.   The effect of electrical stimulation, fasting and anesthesia on the carnitine(s) and acylcarnitines of rat white and red skeletal muscle fibers.  Comp.Biochem. Physiol., 75:B311-316, 1983.

  • Kerner J and Bieber LL.   A radioisotopic-exchange method for quantitation of short-chain (acid-soluble) acylcarnitines.  Anal.Biochem., 134:459-466, 1983.

  • Sandor A, Kispal Gy, Kerner J, and Alkonyi I.   Combined effect of ascorbic acid deficiency and underfeeding on the hepatic carnitine level in guinea-pigs.  Experientia, 39:512-513, 1983.

  • Kerner J, and Bieber L.L.   Effect of clofibrate on rat liver acylcarnitines. Biochem.Med., 28:204-209, 1982.


    Sandor A, Kerner J, and Alkonyi I.   On carnitine content of human breast milk.  Pediatr.Res., 16:89-91, 1982.

  • Sandor A, Kerner J, and Alkonyi I.   Concurrent occurrence of elevated ketone body and depressed carnitine level in underfed guinea-pigs.  Experientia, 37:933-934, 1981.

  • Sandor A, Kerner J, and Alkonyi I.   Role of carnitine in promoting the effect of antidiabetic biguanides on hepatic ketogenesis.  Biochem. Pharmacol., 28:969-974, 1979.

  • Sandor A, Kerner J, and Alkonyi I.   Effect of a biguanide (buformin) on carnitine palmitoyl-transferase activity. Acta Biochim.Biophys. Acad. Sci. Hung., 12:217-221, 1977.

  • Kerner J, Sandor A, and Alkonyi I.   The effect of denervation on carnitine metabolism in rat skeletal muscle. Acta Biochim.Biophys. Acad. Sci. (Hung.), 11:239-243, 1976.

  • Alkonyi I, Kerner J, and Sandor A.   The possible role of carnitine and carnitine acetyltransferase in the contracting frog skeletal muscle. FEBS Letters, 52:265-268, 1975.

  • Alkonyi I, Kerner J, and Sandor A.   The effect of cold and fasting on the carnitine concentration in the brown adipose tissue of rats. Acta Biochim.Biophys. Acad. Sci. (Hung.), 10:217-220, 1975.

  • Kerner J, Sandor, A., and Alkonyi, I.   Physiological variations in carnitine acetyltransferase activity in rat tissues: activity in animals exposed to fasting and cold. Acta Physiol. Acad. Sci. (Hung.), 43:227-231, 1973.

  • Alkonyi I, Kerner J, and Szabo D.   A new enzymatic method for the determination of acetoacetate. Acta Biochim.Biophys. Acad. Sci. (Hung.), 7 :143-147, 1972.

  • Alkonyi I, Kerner J, Palfi E, and Sandor A.   Notiz über die Spaltung von 5-oxo-3-methyl-2-hexensäure.  Chemische Berichte, 104 :1699-1700, 1971.

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