title: Cobalamin (vitamin B12) and holotranscobalamin changes in plasma and liver tissue in alcoholics with liver disease.
abstract: OBJECTIVE
  We wanted to know if alterations in plasma cobalamin (B12) concentration and B12 carriers, e.g., holotranscobalamins (holo TC), occur in blood and liver tissue from patients with severe alcoholic liver disease. Our purpose was to test the hypothesis that liver disease may disrupt B12 distribution.
  
  
  METHODS
  Total B12, as well as B12 bound to transcobalamin I, II, III (holo TC), were measured to determine their concentration in plasma and in liver tissue; Poteriochromonas malhamensis--a protozoan reagent served to measure only metabolically active (true) B12. Total B12 as distributed in holo TC in plasma and liver tissue of healthy subjects (controls) were compared to patients with severe alcoholic liver disease.
  
  
  RESULTS
  Severe liver disease initiates highly elevated B12 levels in plasma and a lowered liver tissue total B12 concentration. The percent of B12 distributed to holo TC II is significantly depleted during liver disease. In contrast, holo TC I and III are elevated in plasma during liver disease and contain more B12 than controls. Total B12 and B12 distributed to TC are lower in diseased liver tissue.
  
  
  CONCLUSIONS
  Severe alcoholic liver disease involves leakage of total B12 from liver tissue into the plasma. Holo TC I and III concentration increases in plasma; this preserves the high plasma B12 from being excreted. However, plasma holo TC II B12 distribution is decreased, indicating that there is a depression of exogenous B12 entering the plasma and tissues. In severe liver disease, liver tissue B12 binding and storage by TC is disrupted and causes B12 to leak out of the liver into the circulation. Eventually liver disease could produce enough severe tissue B12 deficits to cause metabolic dysfunction despite elevated plasma total B12. Elevation of plasma B12, accompanied by a lowering of holo TC II distribution, seemed to be a useful index of liver disease severity suggesting preventive treatment.
authors.affiliation: Department of Preventive Medicine and Community Health, University of Medicine and Dentistry, New Jersey Medical School, Newark 07107-3001, USA.
authors.forename: H
authors.initials: H
authors.lastname: Baker
authors.forename: C B
authors.initials: CB
authors.lastname: Leevy
authors.forename: B
authors.initials: B
authors.lastname: DeAngelis
authors.forename: O
authors.initials: O
authors.lastname: Frank
authors.forename: E R
authors.initials: ER
authors.lastname: Baker
mesh_terms: D006801:Humans; D008099:Liver / Q000378:metabolism*; D008108:Liver Diseases, Alcoholic / Q000097:blood / Q000378:metabolism*; D014155:Transcobalamins / Q000378:metabolism*; D014805:Vitamin B 12 / Q000097:blood / Q000378:metabolism*
chemical_list: D014155:Transcobalamins; D014805:Vitamin B 12