Alcoholism: Clinical and Experimental ResearchVolume 18, Issue 5 p. 1040-1056 Metabolic Hyperpolarization of Liver by Ethanol: The Importance of Mg2+ and H+ in Determining Impermeant Intracellular Anionic Charge and Energy of Metabolic Reactions Richard L. Veech, Corresponding Author Richard L. Veech Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; and the Department of Physiology, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee.Reprint requests: Richard L. Veech, Ph.D., Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, 12501 Washington Avenue, Rockville MD, 20852-1823.Search for more papers by this authorDenise N. Gates, Denise N. Gates Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; and the Department of Physiology, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee.Search for more papers by this authorCalvin Crutchfield, Calvin Crutchfield Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; and the Department of Physiology, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee.Search for more papers by this authorWilliam L. Gitomer, William L. Gitomer Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; and the Department of Physiology, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee.Search for more papers by this authorYoshihiro Kashiwaya, Yoshihiro Kashiwaya Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; and the Department of Physiology, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee.Search for more papers by this authorM. Todd King, M. Todd King Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; and the Department of Physiology, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee.Search for more papers by this authorRobert Wondergern, Robert Wondergern Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; and the Department of Physiology, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee.Search for more papers by this author Richard L. Veech, Corresponding Author Richard L. Veech Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; and the Department of Physiology, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee.Reprint requests: Richard L. Veech, Ph.D., Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, 12501 Washington Avenue, Rockville MD, 20852-1823.Search for more papers by this authorDenise N. Gates, Denise N. Gates Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; and the Department of Physiology, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee.Search for more papers by this authorCalvin Crutchfield, Calvin Crutchfield Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; and the Department of Physiology, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee.Search for more papers by this authorWilliam L. Gitomer, William L. Gitomer Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; and the Department of Physiology, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee.Search for more papers by this authorYoshihiro Kashiwaya, Yoshihiro Kashiwaya Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; and the Department of Physiology, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee.Search for more papers by this authorM. Todd King, M. Todd King Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; and the Department of Physiology, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee.Search for more papers by this authorRobert Wondergern, Robert Wondergern Laboratory of Metabolism and Molecular Biology, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland; and the Department of Physiology, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee.Search for more papers by this author First published: October 1994 https://doi.org/10.1111/j.1530-0277.1994.tb00081.xCitations: 17 This study was supported in part by the National Institute on Alcohol Abuse and Alcoholism, Grant AA-08867. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat REFERENCES 1 Jones JE, Shane SR, Jacobs WH, Flink EB: Magnesium balance studies in chronic alcoholism. Ann NY Acad Sci pp 934–946, 1968. 2 Knochel JP: Cardiovascular effects of alcohol. Ann Intern Med 98: 849–854, 1983. 3 Altura BM, Altura BT: Peripheral and cerebrovascular actions of ethanol, acetaldehyde and acetate: relationship to divalent cations. Alcohol Clin Exp Res 11: 99–111, 1987. 4 Friedman HS: Alcohol, arrhythmia, and sudden death. 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Conference Article| August 01 1988 Effect of acetate on hepatic inorganic ion content WILLIAM L. GITOMER; WILLIAM L. GITOMER 1Laboratory of Metabolism and Molecular Biology, NIAAA, Rockville, MD 20852, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar RICHARD L. VEECH RICHARD L. VEECH 1Laboratory of Metabolism and Molecular Biology, NIAAA, Rockville, MD 20852, U.S.A. Search for other works by this author on: This Site PubMed Google Scholar Author and article information Publisher: Portland Press Ltd Received: November 25 1987 Online ISSN: 1470-8752 Print ISSN: 0300-5127 © 1988 Biochemical Society1988 Biochem Soc Trans (1988) 16 (4): 577–578. https://doi.org/10.1042/bst0160577 Article history Received: November 25 1987 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn Email Cite Icon Cite Get Permissions Citation WILLIAM L. GITOMER, RICHARD L. VEECH; Effect of acetate on hepatic inorganic ion content. Biochem Soc Trans 1 August 1988; 16 (4): 577–578. doi: https://doi.org/10.1042/bst0160577 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search © 1988 Biochemical Society1988 Article PDF first page preview Close Modal You do not currently have access to this content.

1.1.|The standard total parenteral nutrition, peritoneal dialysis, hemodialysis and many surgical fluids in use today contain 36 to 45 mmd,l-lactate or 2 to 140 mm acetate whereas the normal blood level of d-lactate is 0.02 mml-lactate 0.5 to 5 mm and acetate 0.1 mm. The reasons for the continued use in patients of such unphysiological concentrations of these anions appear to be historic.2.2.|Administration of similar concentrations of these anions to the rat causes widespread metabolic disturbances which mimic many of the untoward complications associated with current parenteral and dialysis therapy. Understanding of the mechanisms attendant upon the metabolism of these anions may serve as a guide for designing improved parenteral fluids for human patients.3.3.|Elevation of blood d-lactate to 5 mm is associated with cerebral dysfunction in human patients.4.4.|Acetate stimulates the release of the inflammatory leukokine, interleukin-1 from human monocytes. Use of 35 to 45 mm acetate in peritoneal dialysis fluids led to peritoneal fibrosis. Patients exposed to acetate containing hemodialysis fluids have 12-fold elevation in their plasma interleukin-1 levels.5.5.|Administration of 20 mm sodium acetate to rats leads to a number of metabolic disturbances similar to those seen in human dialysis patients: 5.1.(a)|Acetate elevates blood glucose in the rat and may contribute to the exacerbation of the carbohydrate intolerance seen in uremic patients.5.2.(b)|Acetate increases the levels of hepatic malonyl CoA, the rate controlling substrate of fatty acid synthesis and may exacerbate the hypertriglyceridemia characteristic of dialysis patients.5.3.(c)|Acetate administration in the rat leads to a decrease in the cytosolic phosphorylation potential, reduction of the redox state of the free cytosolic NAD couple and paradoxical oxidation of the mitochondrial NAD couple in a pattern analogous to that produced by uncouplers of oxidative phosphorylation and may account in part for the elevation of temperature reported in patients undergoing hemodialysis with acetate.5.4.(d)|Acetate administration in the rat leads to an increase in intracellular phosphorylated intermediates, adenine nucleotides, inorganic phosphate, inorganic pyrophosphate, calcium and magnesium. On cessation of acetate metabolism, the inorganic phosphate and calcium accumulated intracellularly leave the intacellular space. In patients undergoing hemodialysis, the blood phosphate returns to predialysis levels, within 6 hr after the completion of treatment, leaving significant numbers of patients with chronic hyperphosphatemia and the multiple complications attendant to that state.6.6.|The major site of calcium and magnesium accumulation in the rat to which sodium acetate has been administered is the mitochondrial matrix where they form insoluble pyrophosphate precipitates. The reason that this occurs is that the concentrations of free mitochondrial [Ca2+] and [Mg2+] are both about 10−3m within the mitochondrial matrix in vivo.7.7.|A consequence of the free mitochondrial [Ca2+] being about 10−3m is that the distribution of free Ca2+ across the mitochondrial membrane appears to be in near equilibrium with a mitochondrial membrane potential of about 125 mV. The square of the gradient of free [Ca2+] across the mitochondrial membrane is also in near equilibrium with the free cytosolic [ΣATP]/[ΣADP][ΣPi].8.8.|Consideration of the effects of the composition of parenteral fluids upon the energy status and metabolism of cells may improve the therapeutic efficiencies of traditional fluids.