Demyelination, vitamin

Neurological symptoms result from demyelination of the spinal cord and are potentially irreversible. The symptoms and signs characteristic of a vitamin B 2 deficiency include paresthesis of the hands and feet, decreased deep-tendon reflexes, unsteadiness, and potential psychiatric problems such as moodiness, hallucinations, delusions, and psychosis. Neuropsychiatric disorders sometimes develop independently of the anemia, particularly in elderly patients. Visual loss may develop as a result of optic atrophy. 

Deficiency of vitamin E is rare it can occur from abnormalities in lipid absorption as well as dietary deficiency. Its deficiency affects the muscular system, causing dystrophy and paralysis and, if the heart is affected, death by myocardial failure. This is probably caused by demyelin-ation of axons due to oxidative damage. Vitamin E is incorporated into chylomicrons within the enterocyte, so that its uptake into cells requires the activity of lipoprotein lipase. 

The story of vitamin B12 began with pernicious anemia, a disease that usually affects only persons of age 60 or more but which occasionally strikes children.3 Before 1926 the disease was incurable and usually fatal. Abnormally large, immature, and fragile red blood cells are produced but the total number of erythrocytes is much reduced from 4-6 x 106 mm-3 to 1- 3 x 106 mm-3. Within the bone marrow mitosis appears to be blocked and DNA synthesis is suppressed. The disease also affects other rapidly growing tissues such as the gastric mucous membranes (which stop secreting HC1) and nervous tissues. Demyelination of the central nervous system with loss of muscular coordination (ataxia) and psychotic symptoms is often observed. 

Myelination is essential to the normal function of sensory neurons. Because the synthesis of normal myelin is dependent on the availability of specific fatty acids, the inclusion of abnormal fatty acids (e.g., odd-chain, branched-chain fatty acids) in myelin may alter neural function or cause premature demyelination. This hypothesis has been put forth to explain the neurological impairment observed in vitamin B12 deficiency (Shevell and Rosenblatt, 1992). 

Demyelination is because of failure of the methylation of arginine of myelin basic protein. The nervous system is especially vulnerable to depletion of S-adenosylmethionine in vitamin B12 deficiency because, unlike other tissues, it contains only methionine synthetase, which is vitamin B12-dependent and not vitamin B12-independent homocysteine methyl transferase that uses betaine as the methyl donor (Section 10.3.4 Weir and Scott, 1995). 

Peters RA (1936) The biochemical lesion in vitamin Bi deficiency, application of modern biochemical analysis in its diagnosis. Lancet 1 1161-1164 Puri V, Chaudhry N, Tatke M, Prakash V (2005) Isolated vitamin E deficiency with demyelinating neuropathy. Muscle Nerve 32(2) 230-235... 

Neurological complications also are associated with vitamin B-12 deficiency and result from a progressive demyelination of nerve cells. The demyelination is thought to result from the increase in methylmalonyl-CoA that result from vitamin B-12 deficiency. Methylmalonyl-CoA is a competitive inhibitor of malonyl-CoA in fatty acid biosynthesis as well as being able to substitute for malonyl-CoA in any fatty acid biosynthesis that may occur. Since the myelin sheath is in continual flux the methylmalonyl-CoA-induced inhibition of fatty acid synthesis results in the eventual destruction of the sheath. The incorporation methylmalonyl-CoA into fatty acid biosynthesis results in branched-chain fatty acids being produced that may severely alter the architecture of the normal membrane structure of nerve cells... 

The main function of vitamin B12 is thought to be in the metabolism of amino acids. Thus, B,2 is involved in the conversion of homocysteine to methionine and in the catabolism of some branched-chain amino acids. The neurological disorder that is usually associated with vitamin B12 deficiency is due to progressive demyelination of nervous tissue, thought to be owing to a build up of the vitamin Bj2 substrate, methylmalonyl CoA. This probably interferes with the formation of the myelin sheath. 

In long-standing cases of vitamin deficiency, pellagra may also affect the spinal cord the lateral and posterior columns are demyelinated leading to ataxia, altered tendon reflexes, and loss of the sense of position. 

Vitamin B is a general term to refer to pyridoxine, pyridoxal, and pyridoxamine. Experimental animals deficient in vitamin B< show a dermatitis, and sometimes a microcytic anemia, hemosiderosis, fatty livers, and demyelinization of nerves. Somewhat similar findings have been reported in man (Nutrition Reviews, 1954a). Vitamin B is synthesized to some extent in man. Some intestinal bacteria may S3mthesize it, while others can produce an antivitamin that would complicate any estimation of requirements, especially requirements to be met by the diet. 

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