Myelin-bound protein

Significant increases in myelin-bound protein (MBP) and dopamine levels were observed in the frontal cortex and striatum during the first week the PKU mice were placed on diet. The approximate levels of Phe and tyrosine at the 1-week time point, then, should be good estimates for the concentrations of Phe and tyrosine that were conducive to the observed recovery in these brain structures. In striatum at the 1-week time point, levels of Phe fell to about 240 m j, (about 1.8-fold above control), and in frontal cortex Phe decreased to about 225 J, (about a threefold elevation above control), lyrosine only rose to 53 and 58% of control in frontal cortex and striatum, respectively, during the first week of the study. These data re-emphasize the point that low brain tyrosine levels do not impede MBP/myelination and dopamine synthesis in the treated PKU brain. 

Mechanism of Action Acts as a coenzyme for various metabolic functions, including fat and carbohydrate metabolism and protein synthesis. Therapeutic Effect Necessary for cell growth and replication, hematopoiesis, and myelin synthesis. Pharmacokinetics In the presence of calcium, absorbed systemically in lower half of ileum. Initially, bound to intrinsicfactor this complex passes down intestine, binding to receptor sites on ileal mucosa. Protein binding High, Metabolized in the liver. Primarily eliminated unchanged in urine. Half-life 6 days. 

The most hydrophobic integral membrane proteins can be extracted into organic solvents such as mixtures of chloroform and methanol. One such proteolipid protein, the 23.5-kDa lipophilin, accounts for over half the protein of myelin.57 182 The purified protein from rat brain contains 66% of nonpolar amino acids and six molecules of covalently bound palmitic acid and other fatty acids per peptide chain in thioester linkage to cysteine side chains. This protein evidently has four transmembrane helical segments with the six fatty acid chains incorporated into the membrane bilayer. It also has cytoplasmic and extracellular loops, one of which binds inositol hexakisphosphate (Ins P-6). (Fig. 11-9).183 The myelin proteolipid is an essential component of the myelin sheath and defects in this protein are associated with some demyelinating diseases57 which are discussed in Chapter 30. 

Essentially similar results have been obtained by Eylar and co-workers " on the biosynthesis of bovine submaxillary mucin. The enzyme is firmly bound to a membrane solubilization by Triton X-100 results in a large increase in enzymic activity." The enzyme was purified by gel filtration, and its properties were studied. Among various substances studied, the only one (besides carbohydrate-free mucins) that was active as the acceptor of 2-acetamido-2-deoxy-D-galactose was a basic protein, called encephalitogen, isolated from bovine, spinal-cord myelin. ... 

The adenosine-3 -phosphate-5 -phosphosulfate (PAPS) generating system could be located in the 105,000 g supernatant of rat brain, whereas the Gal-Cer sulfotransferase remained particle bound. Substrate may be Gal-Cer or lactosyl ceramide. Sulfatides of kidney show a higher metabolic turnover than those in brain. Water-soluble sulfatide, discovered in the 105,000 g supernatant of a brain homogenate, was found to be complexed to certain specific proteins (Hersch-kowitz et al., 1968). It was postulated that this might represent a transport form from the site of biosynthesis to the myelin. 

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