Vitamin deficient cells

Stimulation of Accumulation in Other Vitamin-Deficient Cell Types... 

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. 

Disease States. Rickets is the most common disease associated with vitamin D deficiency. Many other disease states have been shown to be related to vitamin D. These can iavolve a lack of the vitamin, deficient synthesis of the metaboUtes from the vitamin, deficient control mechanisms, or defective organ receptors. The control of calcium and phosphoms is essential ia the maintenance of normal cellular biochemistry, eg, muscle contraction, nerve conduction, and enzyme function. The vitamin D metaboUtes also have a function ia cell proliferation. They iateract with other factors and receptors to regulate gene transcription. 

The chemistry, metabolism, and clinical importance of folic acid have been the subject of many excellent reviews (A7, Gil, H14, H20, Rl). Folic acid deficiency leads to a macrocytic anemia and leucopenia. These symptoms are due to inadequate synthesis of nucleic acid. The synthesis of purine bases and of thymine, required for nucleic acid synthesis, is impaired in folic acid deficiency. Detection of folic acid activity in biologic fluids and tissues is of the utmost importance it distinguishes between the various anemias, e.g., those due to vitamin Bi2 or folic acid deficiency. Because morphology of the abnormal red cell does not help in diagnosing vitamin deficiency, one must rely on assay methods for differential diagnosis. Treatment of pernicious anemia with folic acid has led to subacute combined degeneration of the spinal cord despite... 

Since only a few vitamins can be stored (A, D, E, Bi2), a lack of vitamins quickly leads to deficiency diseases. These often affect the skin, blood cells, and nervous system. The causes of vitamin deficiencies can be treated by improving nutrition and by administering vitamins in tablet form. An overdose of vitamins only leads to hypervita mi noses, with toxic symptoms, in the case of vitamins A and D. Normally, excess vitamins are rapidly excreted with the urine. 

The answer is D. Several vitamin deficiencies can cause anemia due to reduced DNA synthesis in the erythropoietic cells of the bone marrow, especially folic acid and vitamin Bj2 (cobalamin), which are particularly prevalent among elderly patients due to poor diet and reduced absorption. In addition, deficiencies of either folic acid or vitamin Bj2 could produce the megaloblastic anemia seen in this patient. However, the absence of neurologic symptoms, a hallmark of vitamin Bj2 deficiency, makes that diagnosis less likely than folic acid deficiency. 

Direct organ toxicity. Some substances may directly damage cells of a particular organ or system, either because they or their metabolites are specifically toxic to these cells, or because they are concentrated in one area, e.g. the renal fluoride ion toxicity of methoxyflurane, or the liver damage that occurs in paracetamol overdose because of a toxic intermediate product binding to hepatocytes. Secondary effects. Some effects are only indirectly related to the action of the drug, e.g. vitamin deficiency in patients whose gut flora have been modified by broad-spectrum antibiotics. 

In every study, light was required for the effects of the inhibitors to become apparent. Chloroplasts of herbicide-treated plants kept in the dark resembled, in all respects, chloroplasts of the dark-control plants. The modifications produced in chloroplasts are not unique to herbicides. Mineral and vitamin deficiencies, antibiotics, unnatural pyrimidines, and genetic alterations all cause similar aberrant ultrastruetural changes in chloroplasts however, the extent of the disruptions produced by herbicides is more extreme. The changes induced by herbicides are similar in many respects to those that occur in normal senescence, reflecting the characteristic pattern associated with degeneration and death of a cell. 

With biotin-deficient cells low concentrations of acetate will substitute for high concentrations of sucrose in restoring uptake to normal levels (22). Biotin stimulates slightly when provided in addition to acetate. Pantothenate-deficient cells respond dramatically to acetate only in the presence of this vitamin. This behavior probably reflects the involvement of coenzyme A in the process which restores a normal accumulation pattern. 

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. 

Figure 7. Comparative stimulation of glutamic acid, alanine, and proline accumulation in vitamin B6-deficient cells of L. arabinosus at various extracellular sucrose concentrations...

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. 

The uptake and accumulation of various amino acids in Lactobacillus arabinosus have been described. An extensive investigation of this process using cells deficient in vitamin B6, biotin, and pantothenic acid has shown that all these deficiencies markedly alter the transport process. Accumulation capacity is most severely decreased by a vitamin B6 deficiency. The evidence now available indicates that this does not reflect the direct participation of the vitamin in the transport process, but rather is an indirect effect arising from the synthesis of an abnormal cell wall which renders the cell unusually sensitive to osmotic stress. Amino acid transport in vitamin B6-deficient cells is restored to normal levels by raising the extracellular osmotic pressure or by enabling the cells to synthesize additional wall substance. 

Normally there is very little fat in the feces. However, fat content in stools may increase because of various fat malabsorption syndromes. Such increased fat excretion is steatorrhea. Decreased fat absorption may be the result of failure to emulsify food contents because of a deficiency in bile salts, as in liver disease or bile duct obstruction (stone or tumor). Pancreatic insufficiency may result in an inadequate pancreatic lipase supply. Finally, absorption itself may be faulty because of damage to intestinal mucosal cells through allergy or infection. An example of allergy-based malabsorption is celiac disease, which is usually associated with gluten intolerance. Gluten is a wheat protein. An example of intestinal infection is tropical sprue, which is often curable with tetracycline. Various vitamin deficiencies may accompany fat malabsorption syndromes. 

Hlastin is a hydroxyproline containing protein of connective tissue. Unlike collagen, elastin does not form a triple helix. With a vitamin deficiency elaslin continues to be produced and secreted from the cell, but in an underhydroxylated state. The function of the hydroxyl group in eJastin is not dear. 

Treatment of the folate-deficient patient with folic acid permits the early eryth-roblast to divide, producing late erythroblasts and, eventually, reticulocytes and red blood cells. These effects can very easily be detected by examining blood samples taken before and after the injection and determining the percentage of reticulocytes. Normally, the concentration of reticulocytes in the bloodstream is quite low. A burst in the nrunber can be induced by injecting folic acid (0.1 mg) into a folate-deficient patient. It should be pointed out that injecting vitamin B 2 into a Bi2-deficient patient, or folate into some Bi2-deficient patients, can also cause this burst. Thus, the hematological response to vitamin injections is not a reliable indicator of which vitamin deficiency was present. 

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