High serum vitamin B12 binding capacity as a marker of the fibrolamellar variant of hepatocellular carcinoma.

Ten (9.3%) of 107 patients with hepatocellular carcinoma had considerably increased serum unsaturated vitamin B12 binding capacity. All 10 were young (mean 12 years), had no serum alpha-fetoprotein, and no underlying cirrhosis; all had a longer survival compared with patients without increased serum unsaturated vitamin B12 binding capacity in the study. Seven of the 10 patients had fibrolamellar hepatocellular carcinoma, a recently recognised histological variant, which was found in only one young patient without increased serum unsaturated vitamin B12 binding capacity and no alpha-fetoprotein among the remaining 97. This high degree of correlation between increased serum unsaturated vitamin B12 binding capacity and fibrolamellar hepatocellular carcinoma has not been reported before. Increased serum unsaturated vitamin B12 binding capacity may be of considerable help in diagnosis, prognosis, and monitoring treatment of this well-defined group of patients with hepatocellular carcinoma but no alpha-fetoprotein.     

Phospholipid-transfer proteins in human liver and primary liver carcinoma

Investigations have been carried out on phospholipid-transfer activity of the cytosol and the phospholipid composition of subcellular membranes from human liver and primary liver carcinoma. In both human liver and primary liver carcinoma cytosolic fractions, the transfer activity for phosphatidylcholine (PC), phosphatidylethanolamine (PE) and sphingomyelin has been observed for the first time. The transfer rate of PC and PE in normal human liver was almost equal, whereas sphingomyelin-transfer activity was much slower. In carcinoma cells, the transfer activity for PE and PC was significantly enhanced, while sphingomyelin transfer remained unchanged. Comparative investigations with HepG2 cultured cells have revealed a high PE-transfer activity in this cell line. Parallel with the phospholipid-transfer activity modifications in neoplasic cells, changes in the phospholipid composition of microsomes and mitochondria have been observed. The content of PC and PE in hepatocarcinoma cells was decreased in microsomes, while in the mitochondria it was increased. The possible role of the phospholipid-transfer proteins in the maintenance of membrane composition and structure is discussed.     

Localization of vitamin B12 binding in Euglena gracilis

Different fractionation procedures were used to determine the location of vitamin B12 binding sites in Euglena gracilis. Using uptake measurements, cell fractionation, and light and electron microscopy, the cuticle of the cell was found to be the fraction containing the majority of B12 binding sites. The apparent distribution of vitamin binding sites differed according to the cell lysis method used. The cuticle fraction was responsible for the binding of 80% of the vitamin taken up by the cell during both the rapid and the slow phase of uptake. These results suggest that vitamin B12 binding is regulated, in part, at the cuticle level, and support our previous conclusion that the secondary phase of uptake represents the synthesis of new receptor sites and not the unloading of vitamin inside the cell.     

Cobalamin binding proteins in stomach and serum from various animal species data for B12 binding capacities and molecular sizes of the binding proteins.

1. The unsaturated cobalamin-binding capacity of stomach mucosa and serum from 37 animals and the size of the binders have been measured. 2. The binding capacity in stomach mucosa was from 1 to 600 nmole kg-1 wet wt, the highest values occurring in pig, guinea pig, porpoise and earthworm. In serum it varied from 0.4 to 270 nmole 1(-1), the highest values occurring in duck, grass snake, toad and spiny dogfish. 3. The size in terms of Stokes radius of the cobalamin binders in stomach mucosa varied from 1 nm in hagfish (Mr approximately 14,000) to 7 nm in lamprey (Mr approximately 210,000). In serum it was from 1.4 nm (Mr approximately 17,000) to 7.4 nm (Mr approximately 240,000) both in frog.