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Norman B. Javitt

Norman B. Javitt, MD, PhD

Research Professor, Department of Medicine

Research Professor, Department of Pediatrics

metabolic pathways of bile acid synthesis from cholesterol

Bile acid synthesis is the major metabolic pathway for the elimination of cholesterol. In addition to the pathway for bile acids that begins in the liver and is augmented with interruption of the enterohepatic circulation, a regulatory pathway has recently been discovered that begins with the production of 27-hydroxycholesterol in the aortic endothelium, macrophages, and other tissues. Our National Institutes of Health-funded research program is directed at the delineation of all the intermediates in the regulatory pathway and the determination of their biologic effects. We have already shown that 27-hydroxycholesterol is a potent inhibitor of cholesterol synthesis and LDL receptor activity. We are now investigating other biologic effects that may also occur.

A critical enzymatic step in the regulatory pathway is 7a-hydroxycholesterol which is catalyzed by a novel P-450 enzyme recently identified in our laboratory. This enzyme not only modifies the biologic effects of 27-hydroxycholesterol but also prevents the formation of monohydroxy bile acids which are known cholestatic agents. Thus, a second aspect of our research program is the metabolic basis of cholestatic liver disease.

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MD from Duke University

PhD from University of North Carolina

Javitt, Norman B

Pharmacological reviews. 2023 Sep; 75(5):1036-1042

Chen, Lea Ann; Oliva-Hemker, Maria; Radin, Arielle; Weidner, Melissa; O'Laughlin, Brynn D; Sears, Cynthia L; Javitt, Norman B; Hourigan, Suchitra K

Journal of Crohn's & colitis. 2023 Aug 21; 17(8):1364-1368

Javitt, Norman B

American journal of physiology. Gastrointestinal & liver physiology. 2020 11 01; 319(5):G609-G618

O'Mara, Alana E; Johnson, James W; Linderman, Joyce D; Brychta, Robert J; McGehee, Suzanne; Fletcher, Laura A; Fink, Yael A; Kapuria, Devika; Cassimatis, Thomas M; Kelsey, Nathan; Cero, Cheryl; Sater, Zahraa Abdul; Piccinini, Francesca; Baskin, Alison S; Leitner, Brooks P; Cai, Hongyi; Millo, Corina M; Dieckmann, William; Walter, Mary; Javitt, Norman B; Rotman, Yaron; Walter, Peter J; Ader, Marilyn; Bergman, Richard N; Herscovitch, Peter; Chen, Kong Y; Cypess, Aaron M

Journal of clinical investigation. 2020 May 01; 130(5):2209-2219

Marinelli, Raul A; Vore, Mary; Javitt, Norman B

Journal of pharmacology & experimental therapeutics. 2019 Dec; 371(3):713-717

Javitt, Norman B

Scandinavian journal of gastroenterology. 2018 Oct - Nov; 53(10-11):1425-1426

Javitt, Norman B

Steroids. 2015 Dec; 104:61-4

Javitt, Norman B

Advances in physiology education. 2014 Dec; 38(4):279-85