Richard Veech, M.D., Ph.D.
Laboratory of Metabolic Control
5625 Fishers Lane
Room 2S-28A, MSC 9409
Rockville, MD 20852
The Laboratory of Metabolic Control is centrally interested in the mechanisms that underwrite the maintenance of cellular energy homeostasis. Understanding these mechanisms is important because many disease states are characterized by a lowering of the phosphorylation potential (i.e., the ATP/ADPxPi ratio), which can be influenced by inorganic ion gradients across the cellular membrane. The Section's work involves the development of new techniques, which use capillary electrophoresis and mass spectrometry to quantify the products and reactants of metabolic pathways, as well as determine the energy flux through pathways of interest. The Section has used this and other techniques (e.g., "brain blowing") to provide a metabolomic survey of the effects of acetate metabolism on the brain. Importantly, this survey showed that the metabolism of acetate lowers the energy required to hydrolyze ATP. The Section's second area of specialization involves the development of therapeutic ketones. Ketones can be used to treat epilepsy and Parkinson's disease, but ketonic diets are not suitable for patients over 17. Accordingly, the Section has developed a novel ketone body called D-β-hydroxybutyrate. This compound elevates the energy required for ATP hydrolysis, it protects neurons against MPTP (a neurotoxin resulting in Parkinsonism in humans), and it partially inhibits NADH dehydrogenase by rotenone. The section is currently developing other therapeutic ketones for use by the military.
Lendvai N, Pawlosky R, Bullova P, Eisenhofer G, Patocs A, Veech RL, Pacak K. Succinate-to-fumarate ratio as a new metabolic marker to detect the presence of SDHB/D-related paraganglioma: initial experimental and ex vivo findings. Endocrinology. 2014;155(1):27-32.
Veech RL. Ketone esters increase brown fat in mice and overcome insulin resistance in other tissues in the rat. Ann N Y Acad Sci. 2013;1302:42-8.
Nakagawa T, Ge Q, Pawlosky R, Wynn RM, Veech RL, Uyeda K. Metabolite regulation of nucleo-cytosolic trafficking of carbohydrate response element-binding protein (ChREBP): role of ketone bodies. J Biol Chem. 2013;288(39):28358-67.
Kashiwaya Y, Bergman C, Lee JH, Wan R, King MT, Mughal MR, Okun E, Clarke K, Mattson MP, Veech RL. A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer's disease. Neurobiol Aging. 2013;34(6):1530-9.
Srivastava S, Baxa U, Niu G, Chen X, Veech RL. A ketogenic diet increases brown adipose tissue mitochondrial proteins and UCP1 levels in mice. IUBMB Life. 2013;65(1):58-66.