Skip to Main Content
 

Global Search Box

 
 
 
 

ETD Abstract Container

Abstract Header

Vascular Biochemistry of Vitmain B12: Exploring the Relationship between Intracellular Cobalamin and Redox Status in Human Aortic Endothelial Cells

Suarez Moreira, Edward

Abstract Details

2010, PHD, Kent State University, College of Arts and Sciences / School of Biomedical Sciences.

Abstract

Cobalamins (vitamin B12 derivatives) are essential cofactors for two enzymes in mammals: cytosolic methionine synthase and mitochondrial methylmalonyl-CoA mutase. In addition to its function as cofactor, a further role as a modulator of inflammatory and immune processes has been suggested for vitamin B12. Vitamin B12 deficiency is a major health problem in the US population, especially amongst the elderly. The vascular endothelium lacks the transsulfuration pathway and hence, relies solely on the B12-dependent methionine synthase to metabolize homocysteine. Thus, vitamin B12 deficiency is the primary modifiable cause of hyperhomocysteinemia, a risk factor for cardiovascular disease, in the post folate fortification era. Although vitamin B12 has been studied for over half a century, there remains much to be discovered regarding the biochemical pathways that lead to the synthesis of the cobalamin cofactors and the potential roles of vitamin B12 beyond its function as cofactors of methionine synthase and methylmalonyl-CoA mutase. This research project has been designed to shed light on the key intermediates required for the metabolism of B12 in human cardiovascular cells and the effects of B12 status on vascular pathophysiology, independent of its actions as an enzymatic cofactor.

Resúmen

Las cobalaminas (derivados de vitamina B12) se necesitan como cofactores de dos enzimas en mamíferos: la enzima citosólica metionina sintasa y la enzima mitocondrial, metilmalonil-CoA mutasa. Además de la función de la vitamina B12 como cofactor, se especula que tiene un rol como modulador de los procesos inflamatorios y la respuesta inmune. La deficiencia de vitamina B12 es un problema de salud importante en la población de los EEUU, especialmente entre los adultos mayores. El endotelio vascular no posee las enzimas necesarias para tener una vía de transulfuración funcional y por lo tanto sólo puede metabolizar homocisteína por medio de la metionina sintasa dependiente de vitamina B12. En esta era, en la cual las harinas se fortifican con folato, la deficiencia de vitamina B12 es la causa primaria de hiperhomocisteinemia, que es un factor de riesgo para enfermedades cardiovasculares. A pesar de que la vitamina B12 se ha estudiado por más de medio siglo, hay mucho que descubrir acerca de los efectos que las cobalaminas tienen mas allá de sus funciones como cofactores de la metionina sintasa y la metilmalonil-CoA mutasa y con respecto a las vías metabólicas necesarias para la síntesis de estos cofactores. Este proyecto de investigación se diseñó para dilucidar los intermediarios clave necesarios para el metabolismo de B12 en células cardiovasculares humanas y esclarecer el efecto de la vitamina B12 en la fisiopatología vascular independiente de su función como cofactor enzimático.

Nicola E. Brasch, PhD (Committee Chair)
June Yun, PhD (Committee Co-Chair)
Roger B. Gregory, PhD (Committee Member)
William M. Chilian, PhD (Committee Member)
Eric M. Mintz, PhD (Committee Member)
180 p.

Recommended Citations

Citations

  • Suarez Moreira, E. (2010). Vascular Biochemistry of Vitmain B12: Exploring the Relationship between Intracellular Cobalamin and Redox Status in Human Aortic Endothelial Cells [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1270788182

    APA Style (7th edition)

  • Suarez Moreira, Edward. Vascular Biochemistry of Vitmain B12: Exploring the Relationship between Intracellular Cobalamin and Redox Status in Human Aortic Endothelial Cells. 2010. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1270788182.

    MLA Style (8th edition)

  • Suarez Moreira, Edward. "Vascular Biochemistry of Vitmain B12: Exploring the Relationship between Intracellular Cobalamin and Redox Status in Human Aortic Endothelial Cells." Doctoral dissertation, Kent State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=kent1270788182

    Chicago Manual of Style (17th edition)