Pathogenesis of Brain Dysfunction in Deficiency of Thiamine, Riboflavin, Pantothenic Acid, or Vitamin B6

  • John A. Sturman
  • Richard S. Rivlin


We have attempted to review the literature available to date concerning the effects of a deficiency of one of four water-soluble vitamins—thiamine, riboflavin, pantothenic acid, and vitamin B6—on the mammalian system and how such deficiency affects the central nervous system and its functioning. These vitamins are all involved in enzyme systems of the body as coenzymes, and a deficiency therefore results in multiple biochemical disturbances. We have tried to relate these biochemical disturbances, where possible, to the accompanying physical and neurological changes.


Flavin Adenine Dinucleotide Pantothenic Acid Thiamine Deficiency Pyridoxal Phosphate Riboflavin Deficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    E. B. Vedder, “Beriberi,” Wood, New York (1913).Google Scholar
  2. 2.
    V. N. Patwardhan, Nutrition in India, Indian J. Med. Sci. (1952).Google Scholar
  3. 3.
    FAO Nutritional Studies, “Rice Enrichment in the Philippines,” No. 12, (1954).Google Scholar
  4. 4.
    E. O. Carrasco, Beriberi mortality in the Philippines, Nutrition News July–Sept.: 134–141 (1954).Google Scholar
  5. 5.
    R. R. Williams, “Toward the Conquest of Beriberi,” Harvard University Press, Cambridge, Mass. (1961).Google Scholar
  6. 6.
    J. Salcedo, Experience in the etiology and prevention of thiamine deficiency in the Philippine Islands, Ann. N.Y. Acad. Sci. 98:568–575 (1962).Google Scholar
  7. 7.
    C. Bhuvaneswaran and A. Sreenivasan, Problems of thiamine deficiency states and their amelioration, Ann. N.Y. Acad. Sci. 98:576–601 (1962).Google Scholar
  8. 8.
    C. Wernicke, “Lehrbuch der Gehirnkrankheiten für Aerzte und Studirende,” Theodor Fischer, Kassal 2:229–242 (1881).Google Scholar
  9. 9.
    N. Jolliffe, H. Wortis, and H. D. Fein, The Wernicke syndrome, Arch. Neurol. Psychiatr. 46:569–597 (1941).Google Scholar
  10. 10.
    K. Lohmann and P. Schuster, Über die co-carboxylase, Naturwissenschaften 2:26–27 (1937).Google Scholar
  11. 11.
    A. F. Wagner and K. Folkers, “Vitamins and Coenzymes,” Interscience, New York (1964).Google Scholar
  12. 12.
    J. H. Pincus and I. Grove, Distribution of thiamine phosphate esters in normal and thiamine-deficient brain, Exp. Neurol. 28:477–483 (1970).Google Scholar
  13. 13.
    T. Yusa and B. Maruo, Biochemical role of thiamine triphosphoric acid ester, J. Biochem. 60:735–737 (1966).Google Scholar
  14. 14.
    A. von Muralt, The role of thiamine in neurophysiology, Ann. N.Y. Acad. Sci. 98:499–507 (1962).Google Scholar
  15. 15.
    J. R. Cooper and J. H. Pincus, The role of thiamine in nerve conduction, in “Thiamine Deficiency: Biochemical Lesions and their Clinical Significance” (G. E. W. Wolstenholme and M. O’Connor, eds.) pp. 112–121, Ciba Foundation Study Group No. 28, Little, Brown, Boston (1967).Google Scholar
  16. 16.
    B. S. Platt, Clinical features of endemic beriberi, Fed. Proc. 17:8–20 (1958).Google Scholar
  17. 17.
    B. S. Platt, Thiamine deficiency in human beriberi and in Wernicke’s encephalopathy, in “Thiamine Deficiency: Biochemical Lesions and their Clinical Significance” (G. E. W. Wolstenholme and M. O’Connor, eds.) pp. 135–143, Ciba Foundation Study Group No. 28, Little, Brown, Boston (1967).Google Scholar
  18. 18.
    S. Weiss, Occidental beriberi with cardiovascular manifestations: Its relation to thiamine deficiency, J. Am. Med. Assoc. 115:823–839 (1940).Google Scholar
  19. 19.
    R. Peters, Significance of biochemical lesions in the pyruvate oxidase systm, Br. Med. Bull. 9:116–122 (1953).Google Scholar
  20. 20.
    V. Ramalingaswami, Infantile beriberi, Fed. Proc. 17:43–46 (1958).Google Scholar
  21. 21.
    J. D. Spillane, “Nutritional Disorders of the Nervous System,” Williams & Wilkins, Baltimore (1947).Google Scholar
  22. 22.
    L. Alexander, Wernicke’s disease: Identity of lesions produced experimentally by B1 avitaminosis in pigeons with hemorrhagic polioencephalitis occurring in chronic alcoholism in man, Am. J. Pathol. 16:61–69 (1940).Google Scholar
  23. 23.
    H. E. Riggs and R. S. Boles, Wernicke’s disease: A clinical and pathological study of 42 cases, Quart. J. Stud. Alcohol 5:361–370 (1944).Google Scholar
  24. 24.
    A. C. P. Campbell and J. H. Biggart, Wernicke’s encephalopathy (polioencephalitis haemor-rhagica superior): Its alcoholic and nonalcoholic incidence, J. Pathol. Bacteriol. 48:245–262 (1939).Google Scholar
  25. 25.
    G. B. Phillips, M. Victor, R. D. Adams, and C. S. Davidson, A study of the nutritional defect in Wernicke’s syndrome: The effect of a purified diet, thiamine and other vitamins on the clinical manifestations, J. Clin. Invest. 31:859–871 (1952).Google Scholar
  26. 26.
    R. D. Williams, H. L. Mason, R. M. Wilder, and B. F. Smith, Observations on induced thiamine (vitamin B1) deficiency in man, Arch. Intern. Med. 66:785–799 (1940).Google Scholar
  27. 27.
    R. D. Williams, H. L. Mason, B. F. Smith, and R. M. Wilder, Induced thiamine (vitamin B1) deficiency and the thiamine requirement of man, Arch. Intern. Med. 69:721–738 (1942).Google Scholar
  28. 28.
    R. D. Williams, H. L. Mason, M. H. Power, and R. M. Wilder, Induced thiamine (vitamin B1) deficiency in man: Relation of depletion of thiamine to development of biochemical defect and of polyneuropathy, Arch. Intern. Med. 71:38–53 (1943).Google Scholar
  29. 29.
    A. Arnold and C. A. Elvejem, Studies on the vitamin B1 requirements of growing rats, J. Nutr. 15:429–443 (1938).Google Scholar
  30. 30.
    H. M. Evans and S. Lepkovsky, Sparing action of fat on the antineuritic vitamin, Science (Wash. D.C.) 68:298 (1928).Google Scholar
  31. 31.
    G. G. Banergi, Effect of a high-fat diet on the excretion of bisulfite-binding substances in the urine of rats deficient in vitamin B1, Biochem. J. 34:1329–1333 (1940).Google Scholar
  32. 32.
    G. G. Banergi, Effect of diets rich in protein upon rats deprived of vitamin B1, Biochem. J. 35:1354–1357 (1941).Google Scholar
  33. 33.
    T. B. Morgan and J. Yudkin, The vitamin-sparing action of sorbitol, Nature (Lond.) 180:543–545 (1957).Google Scholar
  34. 34.
    T. B. Morgan and J. Yudkin, Thiamine-sparing action of sorbitol in rats and mice, Nature (Lond.) 184:909–910 (1959).Google Scholar
  35. 35.
    C. J. Gubler and G. E. Bethsold, Studies on the physiological functions of thiamine. II. Effects of sorbitol on growth and α-ketoacid metabolism in thiamine-deficient and antagonisttreated rats, J. Nutr. 77:332–342 (1962).Google Scholar
  36. 36.
    J. M. Hundley, L. L. Ashburn, and W. H. Sebrell, The electrocardiogram in chronic thiamine deficiency in rats, Am. J. Physiol. 144:404–414 (1945).Google Scholar
  37. 37.
    C. O. Prickett, The effect of a deficiency of vitamin B1 upon the central and peripheral nervous systems of the rat, Am. J. Physiol. 107:459–470 (1934).Google Scholar
  38. 38.
    C. J. Gubler, Studies on the physiological functions of thiamine. I. The effects of thiamine deficiency and thiamine antagonists on the oxidation of α-ketoacids by rat tissues, J. Biol. Chem. 236:3112–3120 (1961).Google Scholar
  39. 39.
    J. C. Koedam, The mode of action of pyrithiamine as an inductor of thiamine deficiency, Biochim. Biophys. Acta 29:333–344 (1958).Google Scholar
  40. 40.
    P. M. Dreyfus, The quantitative histochemical distribution of thiamine in deficient rat brain, J. Neurochem. 8:139–145 (1961).Google Scholar
  41. 41.
    P. M. Dreyfus and M. Victor, Effects of thiamine deficiency on the central nervous system, Am. J. Clin. Nutr. 9:414–425 (1961).Google Scholar
  42. 42.
    R. C. Collins, J. B. Kirkpatrick, and D. B. McDougal, Some regional pathologic and metabolic consequences in mouse brain of pyrithiamine-induced thiamine deficiency, J. Neuropathol. Exp. Neurol. 29:57–69 (1970).Google Scholar
  43. 43.
    K. V. Jubb, L. Z. Saunders, and H. V. Coats, Thiamine deficiency encephalopathy in cats, J. Comp. Pathol. 66:217–227 (1956).Google Scholar
  44. 44.
    J. F. Rinehart, M. Friedman, and L. D. Greenberg, Effect of experimental thiamine deficiency on the nervous system of the Rhesus monkey, Arch. Pathol. 48:129–139 (1949).Google Scholar
  45. 45.
    G. H. Collins, Glial cell changes in the brain stem of thiamine-deficient rats, Am. J. Pathol. 50:791–802 (1967).Google Scholar
  46. 46.
    D. M. Robertson, S. M. Wasan, and D. B. Skinner, Ultrastructural features of early brain stem lesions of thiamine-deficient rats, Am. J. Pathol. 52:1081–1097 (1968).Google Scholar
  47. 47.
    D. M. Robertson and H. J. Manz, Effect of thiamine deficiency on the competence of the blood-brain barrier to albumin labeled with fluorescent dyes, Am. J. Pathol. 63:393–399 (1971).Google Scholar
  48. 48.
    H. J. Manz and D. M. Robertson, Vascular permeability to horseradish peroxidase in brainstem lesions of thiamine-deficient rats, Am. J. Pathol. 66:565–572 (1972).Google Scholar
  49. 49.
    R. L. Swank, R. R. Porter, and A. Yeomans, The production and study of cardiac failure in thiamine-deficient dogs, Am. Heart J. 22:154–168 (1941).Google Scholar
  50. 50.
    R. H. Follis, M. H. Miller, M. M. Wintrobe, and H. J. Stein, Development of myocardial necrosis and absence of nerve degeneration in thiamine deficiency in pigs, Am. J. Pathol. 19:341–355 (1943).Google Scholar
  51. 51.
    L. L. Ashburn and J. V. Lawry, Development of cardiac lesions in thiamine-deficient rats, Arch. Pathol. 37:27–33 (1944).Google Scholar
  52. 52.
    R. G. Green, W. E. Carlson, and C. A. Evans, A deficiency disease of foxes produced by feeding fish: B1 avitaminosis analogous to Wernicke’s disease of man, J. Nutr. 21:243–256 (1941).Google Scholar
  53. 53.
    C. A. Evans, W. E. Carlson, and R. G. Careen, The pathology of Chastek paralysis in foxes: A counterpart of Wernicke’s hemorrhagic polio encephalitis of man, Am. J. Pathol. 18:79–89 (1942).Google Scholar
  54. 54.
    R. L. Swank, Avian thiamine deficiency: A correlation of the pathology and clinical behaviour, J. Exp. Med. 71:683–702 (1940).Google Scholar
  55. 55.
    J. H. Shaw and P. H. Phillips, Neuropathologic studies of acute and chronic thiamine deficiencies and of inanition, J. Nutr. 29:113–123 (1945).Google Scholar
  56. 56.
    C. L. Gries and M. L. Scott, The pathology of thiamin, riboflavin, pantothenic acid and niacin deficiencies in the chick, J. Nutr. 102:1269–1286 (1972).Google Scholar
  57. 57.
    C. J. Gubler, Enzyme studies in thiamine deficiency, Internat. Z. Vit. Forschung 38:287–303 (1968).Google Scholar
  58. 58.
    D. W. McCandless and S. Schenker, Encephalopathy of thiamine deficiency: Studies of intracerebral mechanisms, J. Clin. Invest. 47:2268–2280 (1968).Google Scholar
  59. 59.
    G. Rindi, L. De Giuseppe, and G. Sciorelli, Thiamine monophosphate, a normal constituent of rat plasma, J. Nutr. 94:447–454 (1963).Google Scholar
  60. 60.
    L. De Caro, G. Rindi, V. Perri, and G. Ferrari, The in vivo effects of pyrithiamine and oxythiamine in the rat, Internat. Z. Vit. Forschung 26:343–352 (1956).Google Scholar
  61. 61.
    L. De Caro, G. Rindi, V. Perri, and G. Ferrari, Effects of pyrithiamine and oxythiamine on the thiamine content of tissues and blood pyruvate in mice, Experientia 12:300–302 (1956).Google Scholar
  62. 62.
    G. Rindi, V. Perri, and L. De Caro, The uptake of pyrithiamine by cerebral tissue, Experientia 17:546–548 (1961).Google Scholar
  63. 63.
    G. Rindi and V. Perri, Uptake of pyrithiamine by tissues of rats, Biochem. J. 80:214–216 (1961).Google Scholar
  64. 64.
    G. Rindi, L. de Giuseppe, and U. Ventura, Distribution and phosphorylation of oxythiamine in rat tissues, J. Nutr. 81:147–154 (1963).Google Scholar
  65. 65.
    G. Rindi and G. Sciorelli, Effects of pyrithiamin injection into the brain of rats, J. Nutr. 100:381–388 (1970).Google Scholar
  66. 66.
    G. Rindi, Le azioni fisiologiche della tiamina, Acta Vitaminol. Enzymol. 25:81–100 (1971).Google Scholar
  67. 67.
    E. P. Steyn-Parvé, The mode of action of some thiamine analogues with antivitamin activity, in “Thiamine Deficiency: Biochemical Lesions and Their Clinical Significance” (G. E. W. Wolstenholme and M. O’Connor, eds.) pp. 26–42, Ciba Foundation Study Group No. 28, Little, Brown, Boston (1967).Google Scholar
  68. 68.
    D. W. Woolley, An enzymatic study of the mode of action of pyrithiamine (neopyrithiamine), J. Biol. Chem. 191:43–54(1951).Google Scholar
  69. 69.
    D. Woolley and R. B. Merrifield, Mise en évidence d’une nouvelle action de la thiamine par l’emploi de la pyrithiamine, Bull. Soc. Chim. Biol. 36:1207–1212 (1954).Google Scholar
  70. 70.
    G. Rindi, G. Sciorelli, and G. Ferrarese, The effects of oxythiamine injection into the brain of rats and a comparison with pyrithiamine similarly injected, Internat. J. Vit. Nutr. Res. 40:31–37 (1970).Google Scholar
  71. 71.
    J. R. Cooper, The role of thiamine in nervous tissue: The mechanism of action of pyrithiamine, Biochim. Biophys. Acta 156:368–373 (1968).Google Scholar
  72. 72.
    C. J. Armett and J. R. Cooper, The role of thiamine in nervous tissue: Effect of antimetabolites of the vitamin on conduction in mammalian nonmyelinated nerve fibers, J. Pharmacol. Exp. Therap. 148:137–143 (1965).Google Scholar
  73. 73.
    C. J. Armett and J. R. Cooper, Effect of thiamine analogues on the electrical activity of the rabbit vagus nerve, Experientia 21:605–607 (1965).Google Scholar
  74. 74.
    R. H. S. Thompson and R. E. Johnson, Blood pyruvate in vitamin B1 deficiency, Biochem. J. 29:694–700 (1935).Google Scholar
  75. 75.
    R. A. Peters and R. H. S. Thompson, Pyruvic acid as an intermediary metabolite in the brain tissue of avitaminous and normal pigeons, Biochem. J. 28:916–925 (1934).Google Scholar
  76. 76.
    J. R. O’Brien and R. A. Peters, Vitamin B1 deficiency in the rat’s brain, J. Physiol. 85:454–463 (1935).Google Scholar
  77. 77.
    R. A. Peters, The biochemical lesion in vitamin B1 deficiency: Application of modern biochemical analysis in its diagnosis, Lancet 1:1161–1165 (1936).Google Scholar
  78. 78.
    B. S. Platt and G. D. Lu, Studies on the metabolism of pyruvic acid in normal and vitamin B1-deficient states. IV. The accumulation of pyruvic acid and other carbonyl compounds in beri-beri and the effect of vitamin B1, Biochem. J. 33:1525–1537 (1939).Google Scholar
  79. 79.
    D. B. Hackel, W. T. Goodale, and J. Kleinerman, Effects of thiamine deficiency on myocardial metabolism in intact dogs, Am. Heart J. 46:883–894 (1953).Google Scholar
  80. 80.
    J. Hollowach, F. Kauffman, M. G. Ikossi, C. Thomas, and D. B. McDougal, The effects of a thiamine antagonist, pyrithiamine, on levels of selected metabolic intermediates and on thiamine-dependent enzymes in brain and liver, J. Neurochem. 15:621–631 (1968).Google Scholar
  81. 81.
    M. Brin, The oxidation of C14-pyruvate and of C14-ribose in thiamine deficient intact rats, Isr. J. Med. Sci. 3:792–799 (1967).Google Scholar
  82. 82.
    H. Mcllwain, “Biochemistry and the Central Nervous System,” Little, Brown, Boston (1966).Google Scholar
  83. 83.
    P. M. Dreyfus, The regional distribution of transketolase in the normal and thiamine deficient nervous system, J. Neuropathol. Exp. Neurol. 24:119–129 (1965).Google Scholar
  84. 84.
    S. E. Geel and P. M. Dreyfus, Thiamine deficiency encephalopathy in the developing rat (in preparation).Google Scholar
  85. 85.
    E. A. Hosein, J. G. Chabrol, and G. Freedman, The effect of thiamine deficiency in rats and pigeons on the content of materials with acetylcholine-like activity in brain, heart and skeletal muscle, Rev. Can. Biol. 25:129–134 (1966).Google Scholar
  86. 86.
    K. V. Speeg, D. Chen, D. W. McCandless, and S. Schenker, Cerebral acetylcholine in thiamine deficiency, Proc. Soc. Exp. Biol. Med. 134:1005–1009 (1970).Google Scholar
  87. 87.
    D. L. Cheney, C. J. Gubler, and A. W. Jaussi, Production of acetylcholine in rat brain following thiamine deprivation and treatment with thiamine antagonists, J. Neurochem. 16:1283–1291 (1969).Google Scholar
  88. 88.
    C. Tanaka and J. R. Cooper, The fluorescent microscopic localization of thiamine in nervous tissue, J. Histochem. Cytochem. 16:362–365 (1968).Google Scholar
  89. 89.
    Y. Itokawa and J. R. Cooper, Thiamine release from nerve membranes by tetrodoxin, Science (Wash. D.C.) 166:759–761 (1969).Google Scholar
  90. 90.
    Y. Itokawa and J. R. Cooper, Ion movements and thiamine in nervous tissue. I. Intact nerve preparations, Biochem. Pharmacol. 19:985–992 (1970).Google Scholar
  91. 91.
    Y. Itokawa and J. R. Cooper, Ion movements and thiamine. II. The release of the vitamin from membrane fragments, Biochim. Biophys. Acta 196:274–284 (1970).Google Scholar
  92. 92.
    Y. Itokawa, R. A. Schulz, and J. R. Cooper, Thiamine in nerve membranes, Biochim. Biophys. Acta 266:293–299 (1972).Google Scholar
  93. 93.
    Y. Itokawa and J. R. Cooper, The enzymatic synthesis of triphosphothiamin, Biochim. Biophys. Acta 158:180–182 (1968).Google Scholar
  94. 94.
    R. L. Barchi and P. E. Braun, A membrane associated thiamine triphosphatase from rat brain, J. Biol. Chem. 247:7668–7673 (1972).Google Scholar
  95. 95.
    J. H. Pincus, Y. Itokawa, and J. R. Cooper, Enzyme-inhibiting factor in subacute necrotizing encephalomyelopathy, Neurology 19:841–845 (1969).Google Scholar
  96. 96.
    M. Hamburgh and L. B. Flexner, Biochemical and physiological differentiation during morphogenesis. XXI. Effect of hypothyroidism and hormone therapy on enzyme activities of the developing cerebral cortex of the rat, J. Neurochem. 1:279–288 (1957).Google Scholar
  97. 97.
    Y. S. Kim and J. P. Lambooy, Induction of a specific enzyme inadequacy in infant rats by the use of a homologue of riboflavin, J. Nutr. 101:819–830 (1971).Google Scholar
  98. 98.
    T. Nagatsu, T. Yamamoto, and M. Harada, Purification and properties of human brain mitochondrial monoamine oxidase, Enzymologia 39:15–25 (1970).Google Scholar
  99. 99.
    M. Harada and T. Nagatsu, Identification of flavin in the purified beef brain mitochondrial monoamine oxidase, Experientia 25:583–584 (1969).Google Scholar
  100. 100.
    H. B. Burch, O. H. Lowry, A. M. Padilla, and A. M. Combs, Effects of riboflavin deficiency and realimentation on flavin enzymes of tissues, J. Biol. Chem. 223:29–45 (1956).Google Scholar
  101. 101.
    S. Schapiro and C. J. Percin, Thyroid hormone induction of α-glycerophosphate dehydro-genase in rats of different ages, Endocrinology 79:1075–1078 (1966).Google Scholar
  102. 102.
    M. J. Blunt and C. P. Wendell-Smith, Glial α-glycerophosphate dehydrogenase and central myelination, Nature (Lond.) 216:605–606 (1967).Google Scholar
  103. 103.
    P. L. Wendell, Distribution of glutathione reductase and detection of glutathione-cystine transhydrogenase in rat tissues, Biochim. Biophys. Acta 159:179–181 (1968).Google Scholar
  104. 104.
    R. S. Rivlin, Medical Progress: Riboflavin metabolism, N. Engl. J. Med. 283:463–472 (1970).Google Scholar
  105. 105.
    K. Kanig, Die vitamine in der neurologie, Bibl. Psychiatr. Neurol. 138:60–89 (1969).Google Scholar
  106. 106.
    T. Arakawa, T. Mizuno, F. Chiba, K. Sakai, S. Watanabe, and T. Tamura, Frequency analysis of electroencephalograms and latency of photically induced average evoked responses in children with ariboflavinosis, Tohoku J. Exp. Med. 94:327–335 (1968).Google Scholar
  107. 107.
    M. K. Horwitt, O. W. Hills, C. C. Harvey, E. Liebert, and D. L. Steinberg, Effects of dietary depletion of riboflavin, J. Nutr. 39:357–373 (1949).Google Scholar
  108. 108.
    M. K. Horwitt, C. C. Harvey, O. W. Hills, and E. Liebert, Correlation of urinary excretion of riboflavin with dietary intake and symptoms of ariboflavinosis, J. Nutr. 41:247–264 (1950).Google Scholar
  109. 109.
    O. W. Hills, E. Liebert, D. L. Steinberg, and M. K. Horwitt, Clinical aspects of dietary depletion of riboflavin, Arch. Intern. Med. 87:682–693 (1951).Google Scholar
  110. 110.
    M. Lane, C. P. Alfrey, C. E. Mengel, M. A. Doherty, and J. Doherty, The rapid induction of human riboflavin deficiency with galactoflavin, J. Clin. Invest. 43:357–373 (1964).Google Scholar
  111. 111.
    R. W. Engle and P. H. Phillips, Lack of nerve degeneration in uncomplicated vitamin B1 deficiency in chick and rat, J. Nutr. 16:585–596 (1938).Google Scholar
  112. 112.
    R. W. Engle and P. H. Phillips, Effect of certain nutritional deficiencies on various phosphorus-containing fractions of chick brain, Proc. Soc. Exp. Biol. Med. 37:553–556 (1937).Google Scholar
  113. 113.
    R. W. Engle and P. H. Phillips, Effect of riboflavin-low diets upon nerves, growth and reproduction in the rat, Proc. Soc. Exp. Biol. Med. 40: 597–598 (1939).Google Scholar
  114. 114.
    G. V. Mann, P. L. Watson, A. McNally, and J. Goddard, Primate nutrition. II. Riboflavin deficiency in the Cebus monkey and its diagnosis, J. Nutr. 47:225–241 (1952).Google Scholar
  115. 115.
    H. R. Street, G. R. Cowgill, and H. M. Zimmerman, Further observations of riboflavin deficiency in the dog, J. Nutr. 22:7–24 (1941).Google Scholar
  116. 116.
    S. W. Lippincott and H. P. Morris, Pathological changes associated with riboflavin deficiency in the mouse, J. Natl. Cancer Inst. 2:601–610 (1942).Google Scholar
  117. 117.
    M. M. Wintrobe, W. H. Buschke, R. H. Follis, Jr., and S. Humphreys, Riboflavin deficiency in swine with special reference to occurrence of cataracts, Bull. Johns Hopkins Hosp. 75:102–114(1944).Google Scholar
  118. 118.
    C. S. Lai and G. A. Ransome, Burning-feet syndrome: Case due to malabsorption and responding to riboflavin, Br. Med. J. 2:151–152 (1970).Google Scholar
  119. 119.
    B. O. Osuntokun, M. J. S. Langman, J. Wilson, and A. Aladetoyinbo, Controlled trial of hydroxocobalamin and riboflavin in Nigerian ataxic neuropathy, J. Neurol. Neurosurg. Psychiatr. 33:663–666 (1970).Google Scholar
  120. 120.
    J. Warkany, Riboflavin deficiency and congenital malformations, in “Riboflavin” (R. S. Rivlin, ed.) Plenum Press, New York, pp. 279–301 (1975).Google Scholar
  121. 121.
    M. Winick, Nutrition and nerve cell growth, Fed. Proc. 29:1510–1515 (1970).Google Scholar
  122. 122.
    J. Warkany and E. Schraffenberger, Congenital malformations induced in rats by maternal riboflavin deficiency. VI. The preventive factor, J. Nutr. 27:477–484 (1944).Google Scholar
  123. 123.
    M. M. Nelson, C. D. C. Baird, H. V. Wright, and H. M. Evans, Multiple congenital abnormalities in the rat resulting from riboflavin deficiency induced by the antimetabolite galactoflavin, J. Nutr. 58:125–134 (1956).Google Scholar
  124. 124.
    H. Kalter, Experimental mammalian teratogenesis, a study of galactoflavin-induced hydrocephalus in mice, J. Morphol. 112:303–317 (1963).Google Scholar
  125. 125.
    T. H. Shephard, R. J. Lemire, O. Aksu, and B. Mackler, Studies of the development of congenital anomalies in embryos of riboflavin-deficient, galactoflavin fed rats. I. Growth and Embryol. Pathol. Teratol. 1:75–92 (1968).Google Scholar
  126. 126.
    R. S. Grainger, B. L. O’Dell, and A. G. Hogan, Congenital malformations as related to deficiencies of riboflavin and vitamin B12, source of protein, calcium to phosphorus ratio and skeletal phosphorus metabolism, J. Nutr. 54:33–48 (1954).Google Scholar
  127. 127.
    T. Muramatsu, M. Ando, and T. Nagatsu, Effects of flavin monosulphate and flavin adenine dinucleotide on the electroencephalogram, Nature (Lond.) 182:457–458 (1958).Google Scholar
  128. 128.
    T. Muramatsu, M. Ando, T. Nagatsu, and K. Yagi, Effects of flavins on the electroencephalogram, J. Neurochem. 4:229–233 (1959).Google Scholar
  129. 129.
    L. Prosky, H. B. Burch, D. Bejrablaya, O. H. Lowry, and A. M. Combs, The effects of galactoflavin on riboflavin enzymes and coenzymes, J. Biol. Chem. 239:2691–2695 (1964).Google Scholar
  130. 130.
    Z. Miller, I. Poncet, and E. Takacs, Biochemical studies on experimental congenital malformations: Flavin nucleotides and folic acid in fetuses and livers from normal and riboflavindeficient rats, J. Biol. Chem. 237:968–973 (1962).Google Scholar
  131. 131.
    S. Fass and R. S. Rivlm, Regulation of riboflavin-metabolizing enzymes in riboflavin deficiency, Am. J. Physiol. 217:988–991 (1969).Google Scholar
  132. 132.
    C. S. Catz, M. R. Juchau, and S. J. Yaffe, Effects of iron, riboflavin and iodide deficiencies on hepatic drug-metabolizing enzyme systems, J. Pharmacol. Exp. Ther. 174:197–205 (1970).Google Scholar
  133. 133.
    S. Leodolter and M. Genner, Monoamine oxidase activity and norepinephrine content of organs from rats fed on a vitamin B2-deficient diet, Arch. Internat. Pharmacol. Ther. 190: 393–401 (1971).Google Scholar
  134. 134.
    W. A. Hill and J. P. Lambooy, The effect of a vitaminlike homologue of riboflavin on succinic acid dehydrogenase activity of brain, Proc. Soc. Exp. Biol. Med. 134:922–925 (1970).Google Scholar
  135. 135.
    G. Potier de Courcy and T. Terroine, Influence de la carence en riboflavine sur la fonction phosphatasique alcaline des organes maternais et foetaux a differents stades de la gestation, Ann. Nutr. Aliment. 22:95–100 (1968).Google Scholar
  136. 136.
    H. Kazuya and T. Nagatsu, Flavins and monoamine oxidase activity in brain, liver and kidney of the developing rat, J. Neurochem. 16:123–125 (1968).Google Scholar
  137. 137.
    R. S. Rivlin, Perinatal development of enzymes synthesizing FMN and FAD, Am. J. Physiol. 216:979–982 (1969).Google Scholar
  138. 138.
    G. Domjan, In vitro biochemical examination of FMN synthesis with the brain homogenate of developing chicken embryo, Enzymologia 31:1–7 (1965).Google Scholar
  139. 139.
    T. Nagatsu, I. Nagatsu-Ishibashi, J. Okuda, and K. Yagi, Incorporation of peripheral administered riboflavine into flavine nucleotides in the brain, J. Neurochem. 14:207–210 (1967).Google Scholar
  140. 140.
    B. Foley, R. E. MacKenzie, and D. B. McCormick, Transport and storage of 14 C-riboflavin in the retina and liver of rats, Proc. Soc. Exp. Biol. Med. 126:715–718 (1967).Google Scholar
  141. 141.
    K. Yagi, T. Nagatsu, and T. Ozawa, Inhibitory action of chlorpromazine on oxidation of d-amino acid in diencephalon part of brain, Nature (Lond.) 177:891–892 (1956).Google Scholar
  142. 142.
    K. Yagi, T. Ozawa, M. Ando, and T. Nagatsu, The effects of flavin adenine dinucleotide on the electroencephalogram modified by chlorpromazine, J. Neurochem. 5:304–306 (1960).Google Scholar
  143. 143.
    S. Gabay and S. R. Harris, Inhibition of flavoenzymes by phenothiazines, Agressologie 9:79–89 (1968).Google Scholar
  144. 144.
    S. Gabay and S. R. Harris, Studies on flavin-adenine dinucleotide-requiring enzymes and phenothiazines. II. Structural requirements for D-amino acid oxidase inhibition, Biochem. Pharmacol. 15:317–322 (1966).Google Scholar
  145. 145.
    S. Gabay and S. R. Harris, Studies of flavin-adenine dinucleotide-requiring enzymes and phenothiazines. III. Inhibition kinetics with highly purified d-amino acid oxidase, Biochem. Pharmacol. 16:803–812 (1967).Google Scholar
  146. 146.
    A. H. Neims and L. Hellerman, Flavoenzyme catalysis, Ann. Rev. Biochem. 39:867–888 (1970).Google Scholar
  147. 147.
    E. Hasanagic and P. Stern, Changes of total flavines in different parts of the rat brain under the influence of oxo-tremorine, Life Sci. 7:921–924 (1968).Google Scholar
  148. 148.
    C. A. Garcia-Argiz, J. M. Pasquini, B. Kaplun, and C. J. Gomez, Hormonal regulation of brain development. II. Effect of neonatal thyroidectomy on succinic dehydrogenase and other enzymes in developing cerebral cortex and cerebellum of the rat, Brain Res. 6:635–646 (1967).Google Scholar
  149. 149.
    R. S. Rivlin and R. Hornibrook, Accelerated development of brain enzymes caused by thyroid hormone, Program of the Fifty-third meeting of the Endocrine Society, June 24–26, p. 42(1971).Google Scholar
  150. 150.
    R. S. Rivlin, Regulation of riboflavin metabolism by thyroid hormone, in “The Neurosciences: Third Study Program” (F. O. Schmidt and F. G. Worden, eds.) pp. 835–840, M.I.T. Press, Cambridge, Mass. (1974).Google Scholar
  151. 151.
    R. S. Rivlin, Y. P. Huang, and R. Chaudhuri, Thyroid hormone enhancement of flavin synthesis in newborn rat brain, Fed. Proc. 32:231 (1973).Google Scholar
  152. 152.
    R. J. Williams, The chemistry and biochemistry of pantothenic acid, Adv. Enzymol. 3:253–287 (1943).Google Scholar
  153. 153.
    R. J. Williams, C. M. Lyman, G. H. Goodyear, J. H. Truesdail, and D. Holaday, “Pantothenic acid,” a growth determinant of universal biological occurrence, J. Am. Chem. Soc. 55:2912–2927 (1933).Google Scholar
  154. 154.
    H. K. Mitchell, H. H. Weinstock, E. E. Snell, S. R. Stanberg, and R. J. Williams, Pantothenic acid. V. Evidence for structure of non-β-alanine portion, J. Am. Chem. Soc. 62:1776–1779 (1940).Google Scholar
  155. 155.
    R. J. Williams, J. H. Truesdail, H. H. Weinstock, E. Rohrman, C. M. Lyman, and C. H. McBurney, Pantothenic acid. II. Its concentration and purification from liver, J. Am. Chem. Soc. 60:2719–2723 (1938).Google Scholar
  156. 156.
    L. C. Norris and R. C. Ringrose, The occurrence of a pellagrous-like syndrome in chicks, Science (Wash. D.C.) 71:643 (1930).Google Scholar
  157. 157.
    D. W. Woolley, H. A. Waisman, and C. A. Elvehjem, Nature and partial synthesis of the chick antidermatitis factor, J. Am. Chem. Soc. 61:977–978 (1939).Google Scholar
  158. 158.
    D. W. Woolley, H. A. Waisman, and C. A. Elvehjem, Studies on the structure of the chick antidermatitis factor, J. Biol. Chem. 129:673–679 (1939).Google Scholar
  159. 159.
    T. H. Jukes, Pantothenic acid and the filtrate (chick anti-dermatitis) factor, J. Am. Chem. Soc. 61:975–976 (1939).Google Scholar
  160. 160.
    T. H. Jukes, The pantothenic acid requirement of the chick, J. Biol. Chem. 129:225–231 (1939).Google Scholar
  161. 161.
    F. Lipmann and N. O. Kaplan, A common factor in the enzymatic acetylation of sulfanilimide and of choline, J. Biol. Chem. 162:743–744 (1946).Google Scholar
  162. 162.
    R. O. Brady, The enzymatic synthesis of fatty acids by aldol condensation, Proc. Natl. Acad. Sci. (USA) 44:993–998 (1958).Google Scholar
  163. 163.
    W. L. Williams, E. Hoff-Jorgensen, and E. E. Snell, Determination and properties of an unidentified growth factor required by Lactobacillus bulgaricus, J. Biol. Chem. 177:933–940 (1949).Google Scholar
  164. 164.
    T. E. King, I. G. Fells, and V. H. Cheldelin, Pantothenic acid studies. VI. A biologically active conjugate of pantothenic acid, J. Am. Chem. Soc. 71:131–135 (1949).Google Scholar
  165. 165.
    W. B. Bean and R. E. Hodges, Pantothenic acid deficiency induced in human subjects, Proc. Soc. Exp. Biol. Med. 86:693–698 (1954).Google Scholar
  166. 166.
    W. B. Bean, R. R. Lubin, and K. Daum, Pantothenic acid deficiency induced in human subjects, J. Lab. Clin. Med. 46:793 (1955).Google Scholar
  167. 167.
    W. B. Bean, R. E. Hodges, and K. Daum, Pantothenic acid deficiency induced in human subjects, J. Clin. Invest. 34:1073–1084 (1955).Google Scholar
  168. 168.
    G. H. M. Thornton, W. B. Bean, and R. E. Hodges, The effect of pantothenic acid deficiency on gastric secretion and motility, J. Clin. Invest. 34:1085–1091 (1955).Google Scholar
  169. 169.
    R. Lubin, K. A. Daum, and W. B. Bean, Studies of pantothenic acid metabolism, Am. J. Clin. Nutr. 4:420–430(1956).Google Scholar
  170. 170.
    R. E. Hodges, M. A. Ohlson, and W. B. Bean, Pantothenic acid deficiency in man, J. Clin. Invest. 37:1642–1657(1958).Google Scholar
  171. 171.
    F. S. Daft and W. H. Sebrell, Hemorrhagic adrenal necrosis in rats on deficient diets, U.S. Public Health Rep. 54:2247–2250 (1939).Google Scholar
  172. 172.
    A. A. Nelson, Hemorrhagic cortical necrosis of adrenals in rats on deficient diets, U.S. Public Health Rep. 54:2250–2256 (1939).Google Scholar
  173. 173.
    P. H. Phillips and R. W. Engel, Some histopathological observations on chicks deficient in the chick anti-dermatitis factor or pantothenic acid, J. Nutr. 18:227–232 (1939).Google Scholar
  174. 174.
    L. L. Ashburn, The effect of administration of pathothenic acid on the histopathology of the filtrate factor deficiency state in rats, U.S. Public Health Rep. 55:1337–1346 (1940).Google Scholar
  175. 175.
    S. W. Lippincott and H. P. Morris, Morphologic changes associated with pantothenic acid deficiency in the mouse, J. Natl. Cancer Inst. 2:39–46 (1941).Google Scholar
  176. 176.
    A. E. Schaefer, J. M. McKibbin, and C. A. Elvehjem, Pantothenic acid deficiency studies in dogs, J. Biol. Chem. 143:321–330 (1942).Google Scholar
  177. 177.
    M. Sullivan and J. Nicholls, Nutritional dermatoses in the rat. VI. The effect of pantothenic acid deficiency, Arch. Dermatol. Syph. 45:917–932 (1942).Google Scholar
  178. 178.
    M. M. Wintrobe, M. H. Miller, R. H. Follis, H. J. Stein, C. Mushatt, and S. Humphreys, Sensory neuron degeneration in pigs. IV. Protection afforded by calcium pantothenate and pyridoxine, J. Nutr. 24:345–366 (1942).Google Scholar
  179. 179.
    M. M. Wintrobe, C. Mushatt, J. L. Miller, L.C. Kolb, H. J. Stein, and H. Lisco, The prevention of sensory neuron degeneration in the pig, with special reference to the role of various liver fractions, J. Clin. Invest. 21:71–84 (1942).Google Scholar
  180. 180.
    R. H. Silber, Studies of pantothenic acid deficiency in dogs, J. Nutr. 27:425–433 (1944).Google Scholar
  181. 181.
    R. H. Follis and M. M. Wintrobe, A comparison of the effects of pyridoxine and pantothenic acid deficiencies on the nervous tissue of swine, J. Exp. Med. 81:539–551 (1945).Google Scholar
  182. 182.
    T. Ram, A histopathologic study of chicks deficient in pantothenic acid, Poult. Sci. 28:425–430 (1949).Google Scholar
  183. 183.
    M. E. Reid and G. M. Briggs, Nutritional studies with the guinea pig, J. Nutr. 52:507–517 (1954).Google Scholar
  184. 184.
    T. F. Zucker, Pantothenic acid deficiency and its effect on the integrity and functions of the intestines, Am. J. Clin. Nutr. 6:65–74 (1958).Google Scholar
  185. 185.
    B. N. Berg, Duodenitis and duodenal ulcers produced in rats by pantothenic acid deficiency, Br. J. Exp. Pathol. 40:371–374 (1959).Google Scholar
  186. 186.
    A. Fidanza, Le azioni fisiologiche dell’acido pantotenico, Acta Vitaminol. Enzymol. 25:135–144 (1971).Google Scholar
  187. 187.
    H. P. Klein and F. Lipmann, The relationship of coenzyme A to lipid synthesis. II. Experiments with rat liver, J. Biol. Chem. 203:101–108 (1953).Google Scholar
  188. 188.
    G. F. Lata and E. Anderson, Effects of prolonged pantothenic acid deprivation upon cholesterol synthesis in the rat, Arch. Biochem. 53:518–520 (1954).Google Scholar
  189. 189.
    L. L. Smith and R. B. Mefford, The pantothenic acid deficient rat. II. Further investigations of acetate-1-C14 metabolism, Tex. Rep. Biol. Med. 13:507–514 (1955).Google Scholar
  190. 190.
    G. D. Novelli and F. Lipmann, Bacterial conversion of pantothenic acid into coenzyme A (acetylation) and its relation to pyruvic oxidation, Arch. Biochem. 14:23–27 (1947).Google Scholar
  191. 191.
    R. E. Olson and N. O. Kaplan, The effect of pantothenic acid deficiency upon the coenzyme A content and pyruvate utlization of rat and duck tissues, J. Biol. Chem. 175:515–529 (1948).Google Scholar
  192. 192.
    R. E. Olson and F. J. Stare, The metabolism in vitro of cardiac muscle in pantothenic acid deficiency, J. Biol. Chem. 190:149–164(1951).Google Scholar
  193. 193.
    P. Gyorgy, Vitamin B2 and pellagra-like dermatitis in rats, Nature (Lond.) 133:498–499 (1934).Google Scholar
  194. 194.
    S. Lepkovsky, Crystalline factor 1, Science (Wash. D.C.) 87:169–170 (1938).Google Scholar
  195. 195.
    E. E. Snell, Chemical structure in relation to biological activities of vitamin B6, Vit. Horm. 16:77–125 (1958).Google Scholar
  196. 196.
    A. Meister, Amino group transfer (survey), in “The Enzymes” (P. D. Mover, H. Lardy, and K. Myrback, eds.) pp. 193–217, Academic Press New York (1960).Google Scholar
  197. 197.
    A. E. Braunstein, Pyridoxal phosphate, in “The Enzymes” (P. D. Moyer, H. Lardy, and K. Myrback, eds.) pp. 113–184, Academic Press, New York (1960).Google Scholar
  198. 198.
    A. Meister, Transamination, Adv. Enzymol. 16:185–246 (1955).Google Scholar
  199. 199.
    A Meister, H. A. Sober, and E. A. Peterson, Activation of purified glutamic-aspartic apotransaminase by crystalline pyridoxamine phosphate, J. Am. Chem. Soc. 74:2385–2386 (1952).Google Scholar
  200. 200.
    A Meister, H. A. Sober, and E. A. Peterson, Studies on the coenzyme activation of glutamicaspartic apotransaminase, J. Biol. Chem. 206:89–100 (1954).Google Scholar
  201. 201.
    S. F. Velick and J. Vavra, Glutamic-oxalacetate transaminase, in “The Enzymes” (P. D. Moyer, H. Lardy, and K. Myrback, eds.) pp. 219–246, Academic Press, New York (1962).Google Scholar
  202. 202.
    R. J. Ellis and D. D. Davies, Glutamic-oxaloacetic transaminase of cauliflower. I. Purification and specificity, Biochem. J. 78:615–623 (1961).Google Scholar
  203. 203.
    D. D. Davies and R. J. Ellis, Glutamic-oxaloacetic transaminase of cauliflower. II. Kinetics and mechanism of action, Biochem. J. 78:623–630 (1961).Google Scholar
  204. 204.
    S. E. Synderman, L. E. Holt, R. Carreto, and K. Jacobs, Pyridoxine deficiency in the human infant, J. Clin. Nutr. 1:200–207 (1953).Google Scholar
  205. 205.
    C. J. Malony and A. H. Parmelee, Convulsions in young infants as a result of pyridoxine (vitamin B6) deficiency, J. Am. Med. Assoc. 154:405–406 (1954).Google Scholar
  206. 206.
    D. B. Coursin, Convulsive seizures in infants with pyridoxine-deficient diet, J. Am. Med. Assoc. 154:406–408 (1954).Google Scholar
  207. 207.
    C. D. May, Vitamin B6 in human nutrition: A critique and an object lesson, Pediatrics 14:269–279 (1954).Google Scholar
  208. 208.
    O. A. Bessey, D. J. D. Adam, and A. E. Hansen, Intake of vitamin B6 and infantile convulsions: A first approximation of requirements of pyridoxine in infants, Pediatrics 20:33–44 (1957).Google Scholar
  209. 209.
    W. W. Hawkins and J. Barsky, An experiment on human vitamin B6 deprivation, Science (Wash. D.C.) 108:284–286 (1948).Google Scholar
  210. 210.
    R. W. Vilter, J. F. Mueller, H. S. Glazer, T. Jarrold, J. Abraham, C. Thompson, and V. R. Hawkins, The effect of vitamin B6 deficiency induced by desoxypyridoxine in human beings, J. Lab. Clin. Med. 42:335–357 (1953).Google Scholar
  211. 211.
    J. F. Mueller and R. W. Vilter, Pyridoxine deficiency in human beings induced with desoxypyridoxine, J. Clin. Invest. 29:193–201 (1950).Google Scholar
  212. 212.
    C. R. Scriver and J. H. Hutchison, The vitamin B6 deficiency syndrome in human infancy: Biochemical and clinical observations, Pediatrics 31:240–250 (1963).Google Scholar
  213. 213.
    D. B. Coursin, Vitamin B6 metabolism in infants and children, Vit. Horm. 22:755–786 (1964).Google Scholar
  214. 214.
    E. Roberts, J. Wein, and D. G. Simonsen, γ-Aminobutyric acid (GABA), vitamin B6, and neuronal function-A speculative synthesis, Vit. Horm. 22:503–559 (1964).Google Scholar
  215. 215.
    J. E. Canham, W. T. Nunes, and E. W. Eberline, Electroencephalographic and central nervous system manifestations of B6 dependency in normal human adults, p. 537, Proc. VI Internat. Congr. Nutr. (1963).Google Scholar
  216. 216.
    J. D. Grabow and H. Linkswiler, Electroencephalographic and nerve-conduction studies in experimental vitamin B6 deficiency in adults, Am. J. Clin. Nutr. 22:1429–1434 (1969).Google Scholar
  217. 217.
    C. Waldinger, Pyridoxine deficiency and pyridoxine dependency in infants and children, Postgrad. Med. 35:415–422 (1964).Google Scholar
  218. 218.
    K. Krishnaswamy, Methionine load test in pyridoxine deficiency, Internat. J. Vit. Nutr. Res. 42:468–475 (1972).Google Scholar
  219. 219.
    G. W. Frimpter, R. J. Andelman, and W. F. George, Vitamin B6 dependency syndromes: New horizons in nutrition, Am. J. Clin. Nutr. 22:794–805 (1969).Google Scholar
  220. 220.
    S. H. Mudd, Pyridoxine-responsive genetic disease, Fed. Proc. 30:970–976 (1971).Google Scholar
  221. 221.
    M. R. Seashore, J. L. Durant, and L. E. Rosenberg, Studies of the mechanism of pyridoxineresponsive homocystinuria, Pediatr. Res. 6:187–196 (1972).Google Scholar
  222. 222.
    G. E. Gaull, J. A. Sturman, and F. Schaffner, Homocystinuria due to cystathionine synthase deficiency: Enzymatic and ultrastructural studies, J. Pediatr. 84:381–390 (1974).Google Scholar
  223. 223.
    M. G. Alton-Mackey and B. L. Walker, Graded levels of pyridoxine in the rat diet during gestation and the physical and neuromotor development of offspring, Am. J. Clin. Nutr. 26:420–428 (1973).Google Scholar
  224. 224.
    M. M. Nelson and H. M. Evans, Effect of pyridoxine deficiency on reproduction in the rat, J. Nutr. 43:281–294 (1951).Google Scholar
  225. 225.
    S. D. Davis, T. Nelson, and T. H. Shepard, Teratogenicity of vitamin B6 deficiency: Omphalocele, skeletal and neural defects, and splenic hypoplasia, Science (Wash. D.C.) 169:1329–1330 (1970).Google Scholar
  226. 226.
    K. Dakshinamurti and M. C. Stephens, Pyridoxine deficiency in the neonatal rat, J. Neurochem. 16:1515–1522 (1969).Google Scholar
  227. 227.
    E. D. Eberle and S. Eiduson, Effect of pyridoxine deficiency on aromatic l-amino acid decarboxylase in the developing rat liver and brain, J. Neurochem. 15:1071–1083 (1968).Google Scholar
  228. 228.
    J. A. Driskell and A. Kirksey, The cellular approach to the determination of pyridoxine requirements in pregnant and non-pregnant rats, J. Nutr. 101:661–668 (1971).Google Scholar
  229. 229.
    W. Y. Moon and A. Kirksey, Cellular growth during prenatal and early postnatal periods in progeny of pyridoxine-deficient rats, J. Nutr. 103:123–133 (1973).Google Scholar
  230. 230.
    J. A. Driskell, L. A. Strickland, C. H. Poon, and D. P. Foshee, The vitamin B6 requirement of the male rat as determined by behavioural patterns, brain pyridoxal phosphate and nucleic acid composition and erythrocyte alanine aminotransferase activity, J. Nutr. 103:670–680 (1973).Google Scholar
  231. 231.
    M. C. Stephens, V. Havlicek, and K. Dakshinamurti, Pyridoxine deficiency and development of the central nervous system in the rat, J. Neurochem. 18:2407–2416 (1971).Google Scholar
  232. 232.
    P. J. Benke, H. L. Fleshood, and H. C. Pitot, Osteoporotic bone disease in the pyridoxinedeficient rat, Biochem. Med. 6:526–535 (1972).Google Scholar
  233. 233.
    C. N. Stewart, D. B. Coursin, and H. N. Bhagavan, Cortical-evoked responses in pyridoxinedeficient rats, J. Nutr. 103:670–680 (1973).Google Scholar
  234. 234.
    F. Rosen, E. Mihich, and C. A. Nichol, Selective metabolic and chemotherapeutic effects of vitamin B6 antimetabolites, Vit. Horm. 22:609–641 (1964).Google Scholar
  235. 235.
    N. Olson, in discussion of Evans and Lepkovsky,(30) Am. J. Clin. Nutr. 4:327–328 (1956).Google Scholar
  236. 236.
    J. K. Tews and R. A. Lovell, The effect of a nutritional pyridoxine deficiency on free amino acids and related substances in mouse brain, J. Neurochem. 14:1–7 (1967).Google Scholar
  237. 237.
    M. Victor and R. A. Adams, The neuropathology of experimental vitamin B6 deficiency in monkeys, Am. J. Clin. Nutr. 4:346–353 (1956).Google Scholar
  238. 238.
    J. F. Rinehart and L. D. Greenberg, Arteriosclerotic lesions in pyridoxine-deficient monkeys, Am. J. Pathol. 25:481–486 (1949).Google Scholar
  239. 239.
    J. F. Rinehart and L. D. Greenberg, Pathogenesis of experimental arteriosclerosis in pyridoxine deficiency, Am. Med. Assoc. Arch. Pathol. 51:12–18 (1951).Google Scholar
  240. 240.
    K. S. McCully and B. D. Ragsdale, Production of arteriosclerosis by homocysteinemia, Am. J. Pathol. 61:1–8 (1970).Google Scholar
  241. 241.
    J. F. Rinehart and L. D. Greenberg, Vitamin B6 deficiency in the Rhesus monkey, Am. J. Clin. Nutr. 4:318–328 (1956).Google Scholar
  242. 242.
    C. W. Mushett and G. A. Emerson, Arteriosclerosis in pyridoxine-deficient monkeys and dogs, Fed. Proc. 15:526 (1956).Google Scholar
  243. 243.
    C. W. Mushett and G. A. Emerson, Arteriosclerosis in pyridoxine-deficient monkeys and dogs, Fed. Proc. 16:367 (1957).Google Scholar
  244. 244.
    E. H. Hughes and R. L. Squibb, Vitamin B6 (pyridoxine) in the nutrition of the pig, J. Anim. Sci. 1:320–325 (1942).Google Scholar
  245. 245.
    T. H. Jukes, Vitamin B6 deficiency in chicks, Proc. Soc. Exp. Biol. Med. 42:180–182 (1939).Google Scholar
  246. 246.
    S. Lepkovsky and F. H. Kratzer, Pyridoxine deficiency in chicks, J. Nutr. 24:515–521 (1942).Google Scholar
  247. 247.
    C. L. Gries and M. L. Scott, The pathology of pyridoxine deficiency in chicks, J. Nutr. 102:1259–1268 (1972).Google Scholar
  248. 248.
    B. Williamson and J. G. Coniglio, The effects of pyridoxine deficiency and of caloric restriction on lipids in the developing rat brain, J. Neurochem. 18:267–276 (1971).Google Scholar
  249. 249.
    D. J. Kurtz, H. Levy, and J. N. Kanfer, Cerebral lipids and amino acids in the vitamin B6-deficient suckling rat, J. Nutr. 102:291–297 (1972).Google Scholar
  250. 250.
    M. Takami, M. Fukioka, H. Wada, and T. Taguchi, Studies on pyridoxine deficiency in rats, Proc. Soc. Exp. Biol. Med. 129:110–117 (1968).Google Scholar
  251. 251.
    H. C. Stoerk, Desoxypyridoxine observations in acute pyridoxine deficiency, Ann. N.Y. Acad. Sci. 52:1302–1317 (1950).Google Scholar
  252. 252.
    E. J. Kuchinskas, A. Horvath, and V. du Vigneaud, An anti-vitamin B6 action of l-penicillamine, Arch. Biochem. Biophys. 68:69–75 (1957).Google Scholar
  253. 253.
    R. Tapia and H. Pasantes, Relationships between pyridoxal phosphate availability, activity of vitamin B6-dependent enzymes and convulsions, Brain Res. 29:111–122 (1971).Google Scholar
  254. 253a.
    M. Perez de la Mora, A. Feria-Velasco, and R. Tapia, Pyridoxal phosphate and glutamate decarboxylase in subcellular particles of mouse brain and their relationship to convulsions, J. Neurochem. 20:1575–1587 (1973).Google Scholar
  255. 254.
    R. A. Bayoumi, J. R. Kirwan, and W. R. D. Smith, Some effects of dietary vitamin B6 deficiency and 4-deoxypyridoxine on γ-aminobutyric acid metabolism in rat brain, J. Neurochem. 19:569–576 (1972).Google Scholar
  256. 255.
    R. A. Bayoumi and W. R. D. Smith, The effects of dietary vitamin B6 deficiency on the development of the γ-aminobutyrate shunt in rat brain, Biochem. J. 127:84P–85P (1972).Google Scholar
  257. 256.
    R. A. Bayoumi and W. R. D. Smith, Some effects of dietary vitamin B6 deficiency on γ-aminobutyric acid metabolism in developing rat brain, J. Neurochem. 19:1883–1897 (1972).Google Scholar
  258. 257.
    R. A. Bayoumi and W. R. D. Smith, Regional distribution of glutamic acid decarboxylase in the developing brain of the pyridoxine-deficient rat, J. Neurochem. 21:603–613 (1973).Google Scholar
  259. 258.
    J. A. Sturman, P. A. Cohen, and G. E. Gaull, Effects of deficiency of vitamin B6 on transsulfuration, Biochem. Med. 3:244–251 (1969).Google Scholar
  260. 259.
    F. C. Brown and P. H. Gordon, A study of l-14 C-cystathionine metabolism in the brain, kidney, and liver of pyridoxine-deficient rats, Biochim. Biophys. Acta 230:434–445 (1971).Google Scholar
  261. 260.
    D. B. Hope, Distribution of cystathionine and cystathionine synthase in rat brain, Fed. Proc. 18:249 (1959).Google Scholar
  262. 261.
    S. Kashiwamata, Brain cystathionine synthase: Vitamin B6 requirement for its enzymic reaction and changes in enzyme activity during early development of rats, Brain Res. 30:185–192 (1971).Google Scholar
  263. 262.
    B. Bergeret, F. Chatagner, and C. Fromageot, Quelques relations entre 1e phosphate de pyridoxal et la dècarboxylation de l’acide cystéine-sulfinique par divers organes du rat normal ou du rat carence en vitamine B6, Biochim. Biophys. Acta 17:128–135 (1955).Google Scholar
  264. 263.
    D. K. Rassin and J. A. Sturman, Cysteine sulfinic acid decarboxylase in rat brain: Effect of vitamin B6 deficiency on soluble and particulate components, Life Sci. (in press).Google Scholar
  265. 264.
    F. Schlenk and E. E. Snell, Vitamin B6 and transamination, J. Biol. Chem. 157:425–426 (1945).Google Scholar
  266. 265.
    J. A. Sturman and L. T. Kremzner, Regulation of Ornithine decarboxylase synthesis: Effect of a nutritional deficiency of vitamin B6, Life Sci. 14:977–983 (1974).Google Scholar
  267. 265a.
    J. A. Sturman and L. T. Kremzner, Polyamine biosynthesis and vitamin B6 deficiency: Evidence for pyridoxal phosphate as coenzyme for S-adenosylmethionine decarboxylase, Biochim. Biophys. Acta 372:162–170 (1974).Google Scholar
  268. 266.
    H. Blaschko, S. P. Datta, and H. Harris, Pyridoxine deficiency in the rat: Liver l-cysteic acid decarboxylase activity and urinary amino acids, Br. J. Nutr. 8:364–371 (1953).Google Scholar
  269. 267.
    H. H. Tallan, S. Moore, and W. H. Stein, L-Cystathionine in human brain, J. Biol. Chem. 230:707–716 (1958).Google Scholar
  270. 268.
    F. Chatagner, H. Tabechian, and B. Bergeret, Répercussion d’une carence en vitamine B6 sur le métabolisme de l’acide L-cystéinesulfinique, in vitro et in vivo, chez le rat, Biochim. Biophys. Acta 13:313–318 (1954).Google Scholar
  271. 269.
    H. Blaschko and D. B. Hope, Excretion of cystathionine in pyridoxine deficiency, Biochem. J. 63:7P (1956).Google Scholar
  272. 270.
    D. B. Hope, l-Cystathionine in the urine of pyridoxine-deficient rats, Biochem. J. 66:486–489 (1957).Google Scholar
  273. 270a.
    G. E. Gaull, Y. Wada, K. Schneidman, D. K. Rassin, H. H. Tallan, and J. A. Sturman, Homocystinuria: Observations on the biosynthesis of cystathionine and homolanthionine, Pediatr. Res. 5:265–273 (1971).Google Scholar
  274. 271.
    H. H. Tallan, T. A. Pascal, K. Schneidman, B. M. Gillam, and G. E. Gaull, Homolanthionine synthesis by human liver cystathionase, Biochem. Biophys. Res. Commun. 43:303–310 (1971).Google Scholar
  275. 272.
    T. A. Pascal, H. H. Tallan, and B. M. Gillam, Hepatic cystathionase: Immunochemical and electrophoretic studies of the human and rat forms, Biochim. Biophys. Acta, 285:48–59 (1972).Google Scholar
  276. 273.
    W. C. Rose and R. L. Wixom, The amino acid requirements of man. XIII. The sparing effect of cystine on the methionine requirement, J. Biol. Chem. 216:763–773 (1955).Google Scholar
  277. 274.
    J. A. Sturman and P. A. Cohen, Cystine metabolism in vitamin B6 deficiency: Evidence of multiple taurine pools, Biochem. Med. 5:245–268 (1971).Google Scholar
  278. 275.
    H. J. DeBey, E. E. Snell, and C. A. Baumann, Studies on the interrelationship between methionine and vitamin B6, J. Nutr. 46:203–214 (1952).Google Scholar
  279. 276.
    J. A. Sturman, P. A. Cohen, and G. E. Gaull, Metabolism of l-35 S-methionine in vitamin B6deficiency: Observations on cystathioninuria, Biochem. Med. 3:510–523 (1970).Google Scholar
  280. 277.
    J. R. Beaton, J. L. Beare, G. H. Beaton, and E. W. McHenry, Studies on vitamin B6. IV. The effect of vitamin B6 on protein synthesis and maintenance in the rat, J. Biol. Chem. 204:715–719 (1953).Google Scholar
  281. 278.
    W. W. Hawkins, V. G. Leonard, and J. E. Maxwell, Protein synthesis in vitamin B6 deficiency in the rat, J. Nutr. 76:231–234 (1962).Google Scholar
  282. 279.
    A. C. Trakatellis and A. E. Axelrod, Effect of pyridoxine deficiency upon valine incorporation into tissue proteins of the rat, J. Nutr. 82:483–488 (1964).Google Scholar
  283. 280.
    H. N. Bhagavan and D. B. Coursin, In vivo incorporation of l-[U-14 C]lysine and l-[U-14 C]leucine into brain proteins in pyridoxine deficiency, Internat. J. Vit. Nutr. Res. 41:231–239 (1971).Google Scholar
  284. 281.
    D. B. Hope, The persistence of taurine in the brains of pyridoxine-deficient rats, J. Neurochem. 1:364–369 (1957).Google Scholar
  285. 282.
    J. A. Sturman, Taurine pool sizes in the rat: Effects of vitamin B6 deficiency and high-taurine diet, J. Nutr. 103:1566–1580 (1973).Google Scholar
  286. 283.
    D. B. Hope, Pyridoxal phosphate as the coenzyme of the mammalian decarboxylase for l-cysteine sulphinic and l-cysteic acids, Biochem. J. 59:497–500 (1955).Google Scholar
  287. 284.
    W. O. Read and J. D. Welty, Synthesis of taurine and isethionic acid by dog heart slices, J. Biol. Chem. 237:1521–1522 (1962).Google Scholar
  288. 285.
    E. J. Peck and J. Awapara, Formation of taurine and isethionic acid in rat brain, Biochim. Biophys. Acta 141:499–506 (1967).Google Scholar
  289. 286.
    H. O. Goodman, A. Wainer, J. S. King, and J. J. Thomas, 35 S 2-Hydroxyethanesulfonic acid (isethionic acid) in urine of human subjects given 35 S-taurine, Proc. Soc. Exp. Biol. Med. 125:109–113 (1967).Google Scholar
  290. 287.
    R. Huxtable and B. Bressler, Taurine and isethionic acid: Distribution and interconversion in the rat, J. Nutr. 102:805–814 (1972).Google Scholar
  291. 288.
    A. N. Davison and L. K. Kaczmarek, Taurinc — A possible neurotransmitter, Nature (Lond.) 234:107–108 (1971).Google Scholar
  292. 289.
    L. K. Kaczmarek and A. N. Davison, Uptake and release of taurine from brain slices, J. Neurochem. 19:2355–2362 (1972).Google Scholar
  293. 290.
    P. Lakdesmaki and S. S. Oja, Effect of electrical stimulation on the influx and efflux of taurine in brain slices of newborn and adult rats, Exp. Brain Res. 15:430–438 (1972).Google Scholar
  294. 291.
    C. Hebb, CNS at the cellular level: Identity of transmitter agents, Ann. Rev. Physiol. 32:165–192 (1970).Google Scholar
  295. 292.
    M. S. Starr and M. J. Voaden, The uptake, metabolism and release of 14 C-taurine by rat retina in vitro, Vision Res. 12:1261–1269 (1972).Google Scholar
  296. 293.
    J. A. Sturman, G. W. Hepner, A. F. Hofmann, and P. J. Thomas, Metabolism of [35] Sataurine in man (in preparation).Google Scholar
  297. 294.
    D. A. Roe, The clinical and biochemical significance of taurine excretion in psoriasis, J. Invest. Dermatol. 39:537–541 (1962).Google Scholar
  298. 295.
    D. A. Roe, Taurine intolerance in psoriasis, J. Invest. Dermatol. 46:420–429 (1966).Google Scholar
  299. 296.
    F. Sicuteri, M. Fanciullacci, G. Franchi, A. Giotti, and A. Guidotti, Taurine as a therapeutic agent in vascular pain, Clin. Med. 77:21–32 (1970).Google Scholar
  300. 297.
    F. Pan, and S. Pai, Dietary vitamin Be and enzymes of methionine metabolism in rat liver, J. Chin. Chem. Soc. 17:46–53 (1970).Google Scholar
  301. 298.
    J. D. Finkelstein and F. T. Chalmers, Pyridoxine effects on cystathionine synthase in rat liver, J. Nutr. 100:467–469 (1970).Google Scholar
  302. 299.
    F. Chatagner, Influences of pyridoxine derivatives on the biosynthesis and stability of pyridoxal phosphate enzymes, Vit. Horm. 28:291–302 (1970).Google Scholar
  303. 300.
    O. Wiss and F. Weber, Biochemical pathology of vitamin B6 deficiency, Vitam. Horm. 22:495–501 (1964).Google Scholar
  304. 301.
    J. J. Volpe and L. Laster, Transsulfuration in fetal and postnatal mammalian liver and brain: Cystathionine synthase, its relation to hormonal influences, and cystathionine, Biol. Neonate 20:385–403 (1972).Google Scholar
  305. 302.
    J. J. Volpe and L. Laster, Transsulfuration in primate brain: Regional distribution of cystathionine synthase, cystathionine and taurine in the brain of the Rhesus monkey at various stages of development, J. Neurochem. 17:425–437 (1970).Google Scholar
  306. 303.
    R. Werman, R. A. Davidoff, and M. H. Aprison, The inhibitory action of cystathionine, Life Sci. 5:1431–1440 (1966).Google Scholar
  307. 304.
    B. J. Key and R. P. White, Neuropharmacological comparison of cystathionine, cysteine, homoserine and alpha-ketobutyric acid in cats, Neuropharmacology 9:349–357 (1970).Google Scholar
  308. 305.
    N. Katunuma, E. Kominami, and S. Kominami, A new enzyme that specifically inactivates apo-protein of pyridoxal enzymes, Biochem. Biophys. Res. Commun. 45:70–75 (1971).Google Scholar
  309. 306.
    E. Kominami, K. Kobayashi, S. Kominami, and N. Katunuma, Properties of a specific protease for pyridoxal enzymes and its biological role, J. Biol. Chem. 247:6848–6855 (1972).Google Scholar
  310. 307.
    M. E. Swendseid, J. Villalobos, and B. Friedrich, Free amino acids in plasma and tissues of rats fed a vitamin Be-deficient diet, J. Nutr. 82:206–208 (1964).Google Scholar
  311. 308.
    T. J. Runyan and S. N. Gershoff, Glycine metabolism in vitamin B6-deficient and deoxypyridoxine-treated rats, J. Nutr. 98:113–118 (1969).Google Scholar
  312. 309.
    H. N. Bhagavan and D. B. Coursin, Effect of pyridoxine deficiency on nucleic acid and protein contents of brain and liver, Int. J. Vit. Nutr. Res. 41:419–423 (1971).Google Scholar
  313. 310.
    D. K. Kurtz and J. N. Kanfer, Composition of myelin lipids and synthesis of 3-keto dihydrosphingosine in the vitamin B6-deficient developing rat, J. Neurochem. 20:963–968 (1973).Google Scholar
  314. 311.
    S. H. Snyder, D. S. Kreuz, V. J. Medina, and D. H. Russell, Polyamine synthesis and turnover in rapidly growing tissues, Ann. N.Y. Acad. Sci. 171:749–771 (1970).Google Scholar
  315. 312.
    A. Raina, J. Jänne, P. Hannonen, and E. Hölttä, Synthesis and accumulation of polyamines in regenerating rat liver, Ann. N. Y. Acad. Sci. 171:697–708 (1970).Google Scholar
  316. 313.
    J. A. Sturman and G. E. Gaull, Polyamine biosynthesis in human fetal liver and brain, Pediatr. Res. 8:231–237 (1974).Google Scholar
  317. 314.
    C. J. van den Berg, G. M. J. van Kempen, J. P. Schade, and H. Veldstra, Levels and intracellular localization of glutamate decarboxylase and γ-aminobutyrate transaminase and other enzymes during the development of the brain, J. Neurochem. 12:863–869 (1965).Google Scholar
  318. 315.
    K. L. Sims, J. Witztum, C. Quick, and F. N. Pitts, Brain 4-amino-butyrate: 2-oxoglutarate aminotransferase: Changes in the developing rat brain, J. Neurochem. 15:667–672 (1968).Google Scholar
  319. 316.
    K. L. Sims and F. N. Pitts, Brain glutamate decarboxylase: Changes in the developing rat brain, J. Neurochem. 17:1607–1612 (1970).Google Scholar

Copyright information

© Plenum Press, New York 1975

Authors and Affiliations

  • John A. Sturman
    • 1
    • 2
  • Richard S. Rivlin
    • 3
  1. 1.Department of Pediatric ResearchInstitute for Basic Research in Mental RetardationStaten IslandUSA
  2. 2.Department of PediatricsMount Sinai School of MedicineNew YorkUSA
  3. 3.Department of Medicine and Institute of Human NutritionCollege of Physicians and Surgeons of Columbia UniversityNew YorkUSA

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