Literature DB >> 30737317

A seven-step plan for becoming a moderately rich and famous biochemist.

William L Smith1.   

Abstract

Omega-6 polyunsaturated fatty acids were identified as essential nutrients in 1930. Their essentiality is largely due to their function as prostaglandin (PG) precursors. I spent most of my career in biochemistry determining how PG biosynthesis is regulated. PGs are lipid mediators formed in response to certain circulating hormones and cytokines. PGs act near their sites of synthesis to signal neighboring cells to coordinate their responses (e.g. when platelets interact with blood vessels). The committed step in PG synthesis is the conversion of a 20-carbon omega-6 fatty acid called arachidonic acid to prostaglandin endoperoxide H2 (PGH2). Depending on the tissue and the hormone or cytokine stimulus, this reaction is catalyzed by either cyclooxygenase-1 or cyclooxygenase-2 (COX-1 or COX-2). Once formed, PGH2 is converted, again depending on the context, to one of several downstream PG subtypes that act via specific G protein-coupled receptors. Nonsteroidal anti-inflammatory drugs (e.g. aspirin, ibuprofen, and naproxen) block PG synthesis by inhibiting COX-1 and COX-2. COX-2 is also inhibited by COX-2-selective inhibitors. Inhibition of COX-1 by low-dose aspirin prevents thrombosis. COX-2 inhibition reduces inflammation and pain. Investigating the mysteries of COXs anchored my scientific career. I attribute my successes to the great good fortune of having been surrounded by people who helped me make the most of my talents. I have written this reflection in a light-hearted fashion as a self-help essay, while highlighting the people and factors that most impacted me during my upbringing and then during my maturation and evolution as a biochemist.
© 2019 Smith.

Entities:  

Keywords:  COX-2; NSAID; arachidonic acid (AA) (ARA); aspirin; celecoxib; cyclooxygenase (COX); eicosanoid; half-sites; lipid mediator; naproxen; omega-3 fatty acid; prostaglandin

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Year:  2019        PMID: 30737317      PMCID: PMC6369280          DOI: 10.1074/jbc.X118.006184

Source DB:  PubMed          Journal:  J Biol Chem        ISSN: 0021-9258            Impact factor:   5.157


  71 in total

1.  Cyclooxygenase-2 gene transcription in a macrophage model of inflammation.

Authors:  Yeon-Joo Kang; Byron A Wingerd; Toshi Arakawa; William L Smith
Journal:  J Immunol       Date:  2006-12-01       Impact factor: 5.422

2.  Interactions of 2-O-arachidonylglycerol ether and ibuprofen with the allosteric and catalytic subunits of human COX-2.

Authors:  Liang Dong; Hechang Zou; Chong Yuan; Yu H Hong; Charis L Uhlson; Robert C Murphy; William L Smith
Journal:  J Lipid Res       Date:  2016-04-08       Impact factor: 5.922

3.  (R)-Profens are substrate-selective inhibitors of endocannabinoid oxygenation by COX-2.

Authors:  Kelsey C Duggan; Daniel J Hermanson; Joel Musee; Jeffery J Prusakiewicz; Jami L Scheib; Bruce D Carter; Surajit Banerjee; J A Oates; Lawrence J Marnett
Journal:  Nat Chem Biol       Date:  2011-11       Impact factor: 15.040

4.  Oxygenation of polyunsaturated fatty acids during prostaglandin biosynthesis by sheep vesicular gland.

Authors:  W L Smith; W E Lands
Journal:  Biochemistry       Date:  1972-08-15       Impact factor: 3.162

5.  Oxygenation of unsaturated fatty acids by the vesicular gland of sheep.

Authors:  M Hamberg; B Samuelsson
Journal:  J Biol Chem       Date:  1967-11-25       Impact factor: 5.157

6.  Crystal Structure of Aspirin-Acetylated Human Cyclooxygenase-2: Insight into the Formation of Products with Reversed Stereochemistry.

Authors:  Michael J Lucido; Benjamin J Orlando; Alex J Vecchio; Michael G Malkowski
Journal:  Biochemistry       Date:  2016-02-19       Impact factor: 3.162

7.  Human cyclooxygenase-2 is a sequence homodimer that functions as a conformational heterodimer.

Authors:  Liang Dong; Alex J Vecchio; Narayan P Sharma; Brice J Jurban; Michael G Malkowski; William L Smith
Journal:  J Biol Chem       Date:  2011-04-05       Impact factor: 5.157

8.  Partnering between monomers of cyclooxygenase-2 homodimers.

Authors:  Chong Yuan; Caroline Jill Rieke; Gilad Rimon; Byron A Wingerd; William L Smith
Journal:  Proc Natl Acad Sci U S A       Date:  2006-04-10       Impact factor: 11.205

9.  Primary structure of prostaglandin G/H synthase from sheep vesicular gland determined from the complementary DNA sequence.

Authors:  D L DeWitt; W L Smith
Journal:  Proc Natl Acad Sci U S A       Date:  1988-03       Impact factor: 11.205

10.  Kinin-induced prostaglandin synthesis by renal papillary collecting tubule cells in culture.

Authors:  F C Grenier; T E Rollins; W L Smith
Journal:  Am J Physiol       Date:  1981-07
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  2 in total

1.  Essentiality of n-6 fatty acids.

Authors:  Harald S Hansen
Journal:  J Biol Chem       Date:  2019-04-26       Impact factor: 5.157

2.  Protective effect of parecoxib sodium against ischemia reperfusion‑induced intestinal injury.

Authors:  Mei Li; Zhi Zheng
Journal:  Mol Med Rep       Date:  2021-09-09       Impact factor: 2.952

  2 in total

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