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Entropy
Volume 14
Issue 12
10.3390/e14122492
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Is Endothelial Nitric Oxide Synthase a Moonlighting Protein Whose Day Job is Cholesterol Sulfate Synthesis? Implications for Cholesterol Transport, Diabetes and Cardiovascular Disease †

by
Stephanie Seneff
1,*,
Ann Lauritzen
2,
Robert Davidson
3 and
Laurie Lentz-Marino
4
1
Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 01890, USA
2
Independent Researcher, Houston, TX 77084, USA
3
Internal Medicine Group Practice, PhyNet, Inc. Longview, TX 75605, USA
4
Biochemistry Laboratory Director, Mount Holyoke College, South Hadley, MA 01075, USA
*
Author to whom correspondence should be addressed.
†
Note added by the Publisher: The editors of the journal have been alerted to concerns over potential bias in opinions and bias in the choice of citation sources used in this article. We note that the authors stand by the content as published. Since the nature of the claims against the paper concern speculation and opinion, and not fraud or academic misconduct, the editors would like to issue an Expression of Concern to make readers aware that the approach to collating literature citations for this article was likely not systematic and may not reflect the spectrum of opinions on the issues covered by the article. Please refer to our policy regarding <a href=\\\'https://www.mdpi.com/about/controversial-articles\\\'>possibly controversial articles.
Entropy 2012, 14(12), 2492-2530; https://doi.org/10.3390/e14122492
Received: 8 October 2012 / Revised: 28 November 2012 / Accepted: 4 December 2012 / Published: 7 December 2012
(This article belongs to the Special Issue Biosemiotic Entropy: Disorder, Disease, and Mortality)
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Abstract

Theoretical inferences, based on biophysical, biochemical, and biosemiotic considerations, are related here to the pathogenesis of cardiovascular disease, diabetes, and other degenerative conditions. We suggest that the “daytime” job of endothelial nitric oxide synthase (eNOS), when sunlight is available, is to catalyze sulfate production. There is a striking alignment between cell types that produce either cholesterol sulfate or sulfated polysaccharides and those that contain eNOS. The signaling gas, nitric oxide, a well-known product of eNOS, produces pathological effects not shared by hydrogen sulfide, a sulfur-based signaling gas. We propose that sulfate plays an essential role in HDL-A1 cholesterol trafficking and in sulfation of heparan sulfate proteoglycans (HSPGs), both critical to lysosomal recycling (or disposal) of cellular debris. HSPGs are also crucial in glucose metabolism, protecting against diabetes, and in maintaining blood colloidal suspension and capillary flow, through systems dependent on water-structuring properties of sulfate, an anionic kosmotrope. When sunlight exposure is insufficient, lipids accumulate in the atheroma in order to supply cholesterol and sulfate to the heart, using a process that depends upon inflammation. The inevitable conclusion is that dietary sulfur and adequate sunlight can help prevent heart disease, diabetes, and other disease conditions. View Full-Text
Keywords: endothelial nitric oxide synthase; diabetes; cardiovascular disease; cholesterol sulfate; lysosomes; autophagy; heparan sulfate; hydrogen sulfide; nitric oxide; glycosaminoglycans endothelial nitric oxide synthase; diabetes; cardiovascular disease; cholesterol sulfate; lysosomes; autophagy; heparan sulfate; hydrogen sulfide; nitric oxide; glycosaminoglycans
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MDPI and ACS Style

Seneff, S.; Lauritzen, A.; Davidson, R.; Lentz-Marino, L. Is Endothelial Nitric Oxide Synthase a Moonlighting Protein Whose Day Job is Cholesterol Sulfate Synthesis? Implications for Cholesterol Transport, Diabetes and Cardiovascular Disease. Entropy 2012, 14, 2492-2530. https://doi.org/10.3390/e14122492

AMA Style

Seneff S, Lauritzen A, Davidson R, Lentz-Marino L. Is Endothelial Nitric Oxide Synthase a Moonlighting Protein Whose Day Job is Cholesterol Sulfate Synthesis? Implications for Cholesterol Transport, Diabetes and Cardiovascular Disease. Entropy. 2012; 14(12):2492-2530. https://doi.org/10.3390/e14122492

Chicago/Turabian Style

Seneff, Stephanie, Ann Lauritzen, Robert Davidson, and Laurie Lentz-Marino. 2012. "Is Endothelial Nitric Oxide Synthase a Moonlighting Protein Whose Day Job is Cholesterol Sulfate Synthesis? Implications for Cholesterol Transport, Diabetes and Cardiovascular Disease" Entropy 14, no. 12: 2492-2530. https://doi.org/10.3390/e14122492

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