Prof. Todd D. Porter

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University of Kentucky
College of Pharmacy
Pharmaceutical Sciences
Associate ProfessorAppointed: 1991
University of Kentucky
Medical Research Centers
Graduate Center for Nutritional Sciences
Associate ProfessorAppointed: 2001
University of Kentucky
Academic Centers
Graduate Center for Toxicology
Associate ProfessorAppointed: 1992
Professional Headshot of Todd D. Porter

Mailing Address

381 Biological/Pharmaceutical Complex
University of Kentucky
789 S Limestone
Lexington, Kentucky 40536-0596
United States

Contact Information

Phone: (859) 257-1137
Fax: (859) 257-7564
tporter@email.uky.edu
http://pharmacy.mc.uky.edu/faculty/ToddPorter.php

Qualifications

Ph.D., University of Illinois at Chicago, Pharmacology, 1981.
B.S., University of Illinois, Biochemistry, 1976.

Expertise and Research Interests

My laboratory is interested in the regulation and activity of enzymes involved in cholesterol synthesis. We use recombinant DNA techniques to express and characterize these enzymes and associated proteins in E. coli. We also use cultured hepatoma cells to evaluate the roles, and regulation, of these enzymes under more physiological conditions. We are particularly interested in how their activity is regulated at the protein level by regulatory proteins (kinases and accessory protein factors) as well as how sterols and botanical products can modulate their activity. Current studies are directed at understanding how green and black tea extracts, as well a policosanol (a mixture of very long straight-chain alcohols) inhibit cholesterol synthesis. General areas of interest include structure-function relationships of proteins, nutritional biochemistry, and molecular toxicology.

Other Expertise

Biochemistry of the cytochrome P450 system, with emphasis on the structure and function of NADPH-cytochrome P450 reductase, the electron donor protein for this system, as well as the role of cytochrome b5 in this system.

Future Research

Mice that lack hepatic cytochrome P450 reductase (POR)expression develop fatty livers, consisting predominantly of triglycerides. It is not clear why loss of POR expression would cause this lipidosis, as a role for POR in triglyceride synthesis and processing has not been discovered. POR is involved in both the synthesis and degradation of cholesterol, and so the connection may lie in disruption of this lipid homeostasis. We have replicated this lipidosis in hepatoma cell culture using an siRNA approach, facilitating investigation into this interesting and unexpected observation.

Industrial Relevance

Ames mutagenicity assays with CYP2E1 and P450 reductase expressed in Salmonella tester strains.

Keywords

COS Keywords:

Biochemistry, Environmental Health, Environmental Medicine, Enzymology, Escherichia Coli, Molecular Biology, Mutagenesis, Pharmaceuticals, Pharmacology, Recombinant Dna, Spectroscopy, Toxicology.

Additional Terms:

Cholesterol Biosynthesis, Cytochrome P450, Expression in E. Coli, Garlic, Policosanol, Selenium Toxicity, Squalene Epoxidase, Tellurium Toxicity.

Memberships

American Society for Pharmacology and Experimental Therapeutics

Previous Positions

1986-1991, Assistant Professor, University of Michigan, Medical School, Biological Chemistry

Funding Received

  • American Heart Association (AHA): Characterization of human squalene monooxygenase, $214,500, Jan 2001 to Dec 2003.
  • NCCAM: Inhibition of cholesterol synthesis by green and black tea, 250,000, 2009 to 2011.
  • NCCAM: Inhibition of cholesterol synthesis by policosanol, $250,000, 2007 to 2009.
  • National Science Foundation (NSF): Strategies to enhance mammalian P450 systems in bacteria, MCB-9808636, $298,948, 1999 to 2002.
  • American Heart Association (AHA): Characterization of human squalene monooxgenase, $69,806, 1999 to 2001.
  • NIH-NIEHS 5 R01 ES-06420: Ames mutagenicity testing with recombinant human P450s, $341,957, 1992 to 1998.

Publications

  • Singh DK, Banerjee S, Porter TD (Oct 2009) Green and black tea extracts inhibit HMG-CoA reductase and activate AMP kinase to decrease cholesterol synthesis in hepatoma cells., The Journal of nutritional biochemistry, 20 (10), 816-22 Abstract
  • Li L, Porter TD (Sep 2009) Chlorzoxazone hydroxylation in microsomes and hepatocytes from cytochrome P450 oxidoreductase-null mice., Journal of biochemical and molecular toxicology, 23 (5), 357-63 Abstract
  • Li, L, Porter, T D (2007) Hepatic cytochrome P450 reductase-null mice reveal a second microsomal reductase for squalene monooxygenase, Arch Biochem Biophys, 461, 76-84
  • Singh, D K (2006) Policosanol inhibits cholesterol synthesis in hepatoma cells by activation of AMP-kinase, J Pharmacol Exp Ther, 318, 1020-1026
  • Singh, D K, Porter, T D (2006) Inhibition of sterol 4-methyl oxidase is the principal mechanism by which garlic decreases cholesterol synthesis, J Nutr, 136, 759S-764S
  • Mokashi V, Porter TD, Supernatant Protein Factor Requires Phosphorylation and Interaction With Golgi to Stimulate Cholesterol Synthesis in Hepatoma Cells., Archives of Biochemistry and Biophysics, 435(1), 175-81, Mar 2005 Abstract
  • Mokashi V, Singh DK, Porter TD, Supernatant Protein Factor Stimulates HMG-CoA Reductase in Cell Culture and in Vitro., Archives of Biochemistry and Biophysics, 433(2), 474-80, Jan 2005 Abstract
  • Mokashi V, Singh DK, Porter TD (Apr 2004) Rat supernatant protein factor-like protein stimulates squalene monooxygenase and is activated by protein kinase A., Biochemical and Biophysical Research Communications, 316 (3), 688-92 Abstract
  • Porter TD, Jud Coon: 35 Years of P450 Research, a Synopsis of P450 History., Drug Metabolism and Disposition: the Biological Fate of Chemicals, 32(1), 1-6, Jan 2004 Abstract
  • Mokashi V, Li L, Porter TD, Cytochrome b5 reductase and cytochrome b5 support the CYP2E1-mediated activation of nitrosamines in a recombinant Ames test, Archives of Biochemistry and Biophysics, 412(1), 147-52, April 2003 Abstract
  • Singh DK, Mokashi V, Elmore CL, Porter TD, Phosphorylation of supernatant protein factor enhances its ability to stimulate microsomal squalene monooxygenase, Journal of Biological Chemistry, 278(8), 5646-51, February 2003 Abstract
  • Elmore CL, Porter TD, Modification of the nucleotide cofactor-binding site of cytochrome P-450 reductase to enhance turnover with NADH in Vivo, Journal of Biological Chemistry, 277(50), 48960-4, December 2002 Abstract
  • Gupta N, Porter TD, Inhibition of human squalene monooxygenase by selenium compounds, Journal of Biochemical and Molecular Toxicology, 16(1), 18-23, 2002 Abstract
  • Porter TD, The roles of cytochrome b5 in cytochrome P450 reactions, Journal of Biochemical and Molecular Toxicology, 16(6), 311-6, 2002 Abstract
  • Cooper MT, Porter TD, Cytochrome b(5) coexpression increases the CYP2E1-dependent mutagenicity of dialkylnitrosamines in methyltransferase-deficient strains of Salmonella typhimurium, Mutation Research, 484(1-2), 61-8, December 2001 Abstract
  • Gupta N, Porter TD, Garlic and garlic-derived compounds inhibit human squalene monooxygenase, Journal of Nutrition, 131(6), 1662-7, June 2001 Abstract
  • Laden BP, Porter TD, Inhibition of human squalene monooxygenase by tellurium compounds: evidence of interaction with vicinal sulfhydryls, Journal of Lipid Research, 42(2), 235-40, February 2001 Abstract
  • Laden BP, Porter TD, Resveratrol inhibits human squalene monooxygenase, Nutrition Research, 21, 747-753, 2001
  • Laden BP, Tang Y, Porter TD, Cloning, heterologous expression, and enzymological characterization of human squalene monooxygenase, Archives of Biochemistry and Biophysics, 374(2), 381-8, February 2000 Abstract
  • Porter TD, Correlation between codon usage, regional genomic nucleotide composition, and amino acid composition in the cytochrome P-450 gene superfamily, Biochimica Et Biophysica Acta, 1261(3), 394-400, April 1995 Abstract
  • Porter TD, Coon MJ, Cytochrome P-450. Multiplicity of isoforms, substrates, and catalytic and regulatory mechanisms, Journal of Biological Chemistry, 266(21), 13469-72, July 1991 Abstract
  • Porter TD, An unusual yet strongly conserved flavoprotein reductase in bacteria and mammals, Trends in Biochemical Sciences, 16(4), 154-8, April 1991 Abstract
  • Porter TD, Kasper CB, Coding Nucleotide Sequence of Rat NADPH-cytochrome P-450 Oxidoreductase CDNA and Identification of Flavin-binding Domains., Proceedings of the National Academy of Sciences of the United States of America., 82(4), 973-7, Feb 1985 Abstract

Profile Details

Last Verified: 2/4/2010

COS Expertise ID #541985
Reference this profile directly: http://myprofile.cos.com/tporter