Amino acid, accumulation vitamin

The uptake and accumulation of various amino acids in Lactobacillus arabinosus have been described. Deficiencies of vitamin B6, biotin, and pantothenic acid markedly alter the operation of these transport systems. Accumulation capacity is decreased most severely by a vitamin B6 deficiency. This effect appears to arise indirectly from the synthesis of abnormal cell wall which renders the transport systems unusually sensitive to osmotic factors. Kinetic and osmotic experiments also exclude biotin and pantothenate from direct catalytic involvement in the transport process. Like vitamin B6, they affect uptake indirectly, probably through the metabolism of a structural cell component. The evidence presented supports a concept of pool formation in which free amino acids accumulate in the cell through the intervention of membrane-localized transport catalysts. 

Earlier investigation of environmental factors which modify the accumulation capacity of LB6 cells foreshadowed much of these findings. Specifically, it was observed that conditions which favor cell wall biosynthesis promote a large increase in amino acid accumulation capacity. These observations originated in the initial studies on osmotic protection when it was observed that LB6 cells washed with vitamin B6-... 

Further support comes from the studies relating cell wall biosynthesis and amino acid accumulation capacity in vitamin B6-deficient cells, since it is difficult to account for these observations without attributing considerable osmotic activity to the accumulated amino acids. Any description of accumulation which invokes amino acid attachment to intracellular binding sites, whose affinity can be reduced by a vitamin B6 deficiency, must account for the stimulation of uptake that accompanies the synthesis of essentially extracellular cell wall material. If the reduction in affinity occurs because the cell interior becomes overhydrated (a reasonable postulate which follows from the osmotic experiments), the beneficial effect of wall synthesis is not readily explicable, since vitamin B6-deficient cells have a swollen appearance which is not significantly altered after wall synthesis has been stimulated. Thus, the existing overhydration within the cell probably is not reversed by this change. In contrast, the deposition of additional wall substance would prevent further unfavorable consequences of swelling such as membrane distention, and, in this way, forestall the premature cessation of amino acid accumulation. 

Many kinds of amino acids (eg, L-lysine, L-omithine, t-phenylalanine, L-threonine, L-tyrosine, L-valine) are accumulated by auxotrophic mutant strains (which are altered to require some growth factors such as vitamins and amino acids) (Table 6, Primary mutation) (22). In these mutants, the formation of regulatory effector(s) on the amino acid biosynthesis is genetically blocked and the concentration of the effector(s) is kept low enough to release the regulation and iaduce the overproduction of the corresponding amino acid and its accumulation outside the cells (22). 

Vitamins and minerals, whose main dietary sources are other than fruits and vegetables, are also likely to play a significant role in the prevention and repair of DNA damage, and thus are important to the maintenance of long-term health. Vitamin B12 is found in animal products, and deficiencies of B12 cause a functional folate deficiency, accumulation of the amino acid homocysteine (a risk factor for heart disease),46 and chromosome breaks. B12 supplementation above the RDA was necessary to minimize chromosome breakage.47 Strict vegetarians are at increased risk for developing vitamin B12 deficiency. 

Vitamin B1 is required in humans for two essential enzymatic reactions Ihe synthesis of methionine and the isomerization of methylmalonyl CcA that is produced during the degradation of some amino acids, and fatly acids with odd numbers of carbon atoms (Figure 28.5). When the vitamin is deficient, abnormal fatty acids accumulate and become incorporated into cell membranes, including those of the nervous system. This may account for some of the neurologic manifestations of vitamin P12 deficiency. 

Since we have been unable to detect changes in other cell fractions which correlate with improvements in accumulation capacity, it appears reasonable to conclude, especially in view of the previously cited osmotic evidence, that a lack in cell wall rigidity limits the accumulation capacity of LB6 cells and that the repair of the wall defect suffices to permit these cells to express normal accumulation capacity. On the question of the participation of vitamin B6 in amino acid transport, these, and especially the osmotic experiments, are clearly inconsistent with the suggested catalytic role of this substance directly in the entry reaction. 

Therefore, the three vitamin deficiencies so far studied in detail appear to affect amino acid transport and accumulation in similar but indirect ways. The accumulation defect is most pronounced in vitamin B6-deficient cells, for which there is also strong evidence implicating an abnormality in cell wall composition as a likely source of the change in transport activity. Direct evidence for a cell wall change in biotin- and pantothenate-deficient cells has not yet been obtained. The possibility remains, therefore, that the change in accumulation activity may be caused by an abnormality in some other structural component such as the peripheral cell membrane. 

Lipid peroxidation is increased in vitamin E deficiency, and subsequent catabolism of the peroxides results in the formation of malondialdehyde and other aldehydes. These can form Schiff bases with amino groups of proteins, free amino acids, and nucleic acids. The resultant fluorescent pigments are called ceroid pigments, lipopigments, or lipofuscin, and accumulate in increased amounts in the liver and other tissues of deficient animals (Manwaring andCsallany, 1988). 

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