Lipids metabolic turnover

Dawidowicz, E. A., 1987. Dynamics of membrane lipid metabolism and turnover. Annual Review of Biochemistry 56 43—61. 

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. 

Familial demyelinative/dysmyelinative and axonal neuropathies may also be caused by impaired lysosomal lipid metabolism. Metachromatic leukodystrophy (sulfatide lipidosis) results from mutations of the arylsulfatase A gene, which encodes a lysosomal enzyme required for sulfatide turnover. Myelin is affected in both CNS and PNS, though dysfunction is restricted to the PNS in some patients, and the onset of symptoms can occur at any time between infancy and adulthood. Bone marrow transplantation can slow disease progression and improve nerve conduction velocities [57]. (See in Ch. 41.)... 

CN133 Oliveros, L. B., A. M. Videla, and M. S. Gimenez. Effect of dietary fat saturation on lipid metabolism, arachi-donic acid turnover, and peritoneal macrophage oxidative stress in mice. Braz J Med Biol Res 2004 37(3) 311-320. 

The polar lipids of membranes undergo constant metabolic turnover, the rate of their synthesis normally counterbalanced by the rate of breakdown. The breakdown of lipids is promoted by hydrolytic enzymes in lysosomes, each enzyme capable of hydrolyzing a specific bond. When sphingolipid degradation is impaired by a defect in one of these enzymes (Fig. 1), partial breakdown products accumulate in the tissues, causing serious disease. 

It is apparent that at this stage of development definitive conclusions are premature, and that this aspect of amino acid and lipide metabolism will be pursued vigorously in the near future. It is of considerable interest to us that biotin and pantothenic acid deficiencies affect amino acid transport in L. arabinosus, since both vitamins are known to play a prominent role in lipide biosynthesis. We are currently reexamining the turnover of lipide fractions in nutritionally normal and vitamin-deficient cell types to determine whether there is some relation between this aspect of metabolism and amino acid transport. In any case, the nature of the catalytic steps involved in amino acid transport is still unknown to us. They probably occur in the peripheral cell membrane, but even this elementary and widely accepted belief will require additional study before it can be accepted beyond doubt as an established fact. 

A review of the biosynthesis of Vitamin K and other naturally occurring naphthoquinones and an outline of recent work on the induction of biosynthesis, metabolic turnover, and kinetics of formation of this vitamin and other prenyl lipids have appeared. The prenylation of 4-hydroxybenzoate has been further studied.A cell-free extract of Euglena gracilis could synthesize nona- and octa-prenyltoluquinol from homogentisate and a Micrococcus luteus extract that had been pre-incubated with IPP. The same system produced 2-deca-, 2-nona-, and 2-octa-prenyl forms of 4-carboxy-2-polyprenylphenoI when p-hydroxybenzoate... 

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). 

Thyroid hormones act on tissues all over the body and have far-reaching effects on energy metabolism, turnover of proteins, lipids and carbohydrates and consequently growth. Thyroid deficiency in early childhood, if untreated, leads to stunted growth and poor development of the nervous system. Such individuals are termed cretins. This is a word that has unfortunately passed into common usage as a term of abuse but refers to a specific clinical condition brought about by endocrine insufficiency. 

The metabolic turnover of phosphoinositides in numerous tissues has received a great deal of attention with particular interest being focused on the polar head groups of the lipids. IThat has received comparatively little attention, however, is the fatty acid turnover and the mechanisms for regulation of the molecular species of these lipids. In a number of tissues arachidonic acid is the predominant unsaturated fatty acid of each of the inositides and in rat brain this is a unique feature of the inositides. Not only is arachidonate an important fatty acid, but it seems of importance for the cell to position arachidonate in position - 2 of the phos-phoinositide molecule. 

In spite of a relatively concerted effort recently directed to the study of plant lipid metabolism, many important and interesting questions remain unanswered. For a variety of reasons, plants often seem more intransigent than animals in yielding up their secrets. Our laboratory has initiated a study of membrane lipid synthesis and turnover in a simple eukaryotic green alga, Dunaliella salina, hoping that the ease of experimentation with it will lead to new and widely applicable knowledge. 

In lipid metabolism the turnover of triacylglycerols in adipose tissue has been examined as a possible substrate cycle but it is difficult to see how this could be quantitatively important. Much attention has been focused on brown adipose tissue, since it is known to be important in the generation of heat to maintain body temperature in new-born animals (Figure 5.23). Brown adipose tissue mitochondria are able to generate large quantities of heat because electron transport is largely uncoupled from oxidative... 

Besides water, the diet must provide metabolic fuels (mainly carbohydrates and lipids), protein (for growth and turnover of tissue proteins), fiber (for roughage), minerals (elements with specific metabolic functions), and vitamins and essential fatty acids (organic compounds needed in small amounts for essential metabolic and physiologic functions). The polysaccharides, tri-acylglycerols, and proteins that make up the bulk of the diet must be hydrolyzed to their constituent monosaccharides, fatty acids, and amino acids, respectively, before absorption and utilization. Minerals and vitamins must be released from the complex matrix of food before they can be absorbed and utifized. 

F. H. Westheimer (1987) has provided a detailed survey of the multifarious ways in which phosphorus derivatives function in living systems (Table 4.7). The particular importance of phosphorus becomes clear when we remember that the daily turnover of adenosine triphosphate (ATP) in the metabolic processes of each human being amounts to several kilograms Phosphate residues bond two nucleotides or deoxynucleotides in the form of a diester, thus making possible the formation of RNA and DNA the phosphate always contains an ionic moiety, the negative charge of which stabilizes the diester towards hydrolysis and prevents transfer of these molecules across the lipid membrane. 

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