Metabolic turnover time

Myelin components exhibit great heterogeneity of metabolic turnover. One of the novel characteristics of myelin demonstrated in early biochemical studies was that its overall rate of metabolic turnover is substantially slower than that of other neural membranes [1]. A standard type of experiment was to evaluate lipid or protein turnover by injecting rat brains with a radioactive metabolic precursor and then follow loss of radioactivity from individual components as a function of time. Structural lipid components of myelin, notably cholesterol, cerebro-side and sulfatide, as well as proteins of compact myelin, are relatively stable, with half-lives of the order of many months. One complication in interpreting these studies is that the metabolic turnover of individual myelin components is multiphasic - consisting of an initial rapid loss of radioactivity followed by a much longer slower loss. 

For intracellular enzymes, the picture is compficated because we do not have a clear idea of physiological substrate concentrations and turnover times inside cells indeed, compartmentalization, metabolic channeling, and tight couphng of reactions make it difficult to estimate intracellular concentrations even under ideal conditions (Albe et al., 1990 Srere, 1987). For these reasons, intracellular enzyme assays are typically run at saturating substrate concentrations (i.e., assays) ... 

LDL-receptor deficiency. In the normal condition (a), VLDL produced by the liver loses triacylglycerol as free fatty acids (FFA) via lipoprotein lipase to peripheral tissues and then proceeds down the metabolic cascade to IDL and LDL. A major portion of these two lipoprotein species is taken up by the liver or peripheral tissues via the LDL (apo B, E) receptor. In individuals with down-regulated or genetically defective LDL receptors (b), the residence time in the plasma of IDL is increa.sed, a greater proportion being converted to LDL. LDL production and turnover time are increased, and total plasma cholesterol levels become grossly abnormal. 

Recent studies confirm the initial observations of a decade ago that the turnover of myelin in adults is extremely slow. Myelin as a whole can be considered relatively stable, but various components are metabolized at different rates. The turnover rates (as measured by metabolic half-lives) of phosphotidylcholine, phosphotidylethanolainine, and phosphotidylserine are at least one-half as fast in myelin as in microsomes. Other lipids most probably turn over more slowly. Most lipids have turnover times in myelin on the order of weeks or months. Proteins have similar turnover times. In summary, the original proposal that myelin has a long-term metabolic stability appears accurate. However, various components turn over at different rates, and each component undergoes two phases, one of slow and one of fast degradation. Further information on the biochemistry, ultrastructure, and metabolism of myelin can be found in Bunge (1968), Davison and Peters (1970), Morell (1977), and Norton (1975). 

Whereas some characteristics and properties of CETP have been defined, many questions remain to be answered. We do not yet know the origin of the protein, the nature of factors that regulate its concentration in the plasma, its turnover time, the origin and metabolism of its inhibitor, or even the fundamental question of its physiological role in the plasma. A great deal more investigation into CETP is clearly warranted. 

From flux calculations at this Sargasso Sea station, Gagosian and Nigrelli (1979) found that a maximum of 0.05—0.3% of the sterols produced by phytoplankton in surface waters are deposited to the ocean floor. A similar calculation was done for hydrocarbons by Farrington and Tripp (1977) and found to be 0.01—1%. The sterol residence time (the average lifetime of a sterol molecule before it is metabolized) in the euphotic zone was calculated to be approximately one month, whereas the deep-water residence time value was found to be 20—150 years. This monthly turnover of surface water sterols is in contrast with that of more labile dissolved organic compounds such as amino acids whose turnover time has been estimated to be on the order of several days (Lee and Bada, 1977). 

Cultured skin fibroblasts from a case in which chondroitin 4- and 6-sulfates are excreted in excess (see p. 89) are severely deficient in S-D-glucuronidase activity (H4), these fibroblasts showing an excessive accumulation and lengthened turnover time of sulfate-containing glycos-aminoglycan. The abnormal glycosaminoglycan metabolism can be cor-... 

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