Skip to main content
SpringerLink
Log in

Importance of Fetal and Neonatal Iron: Adequacy for Normal Development of Central Nervous System

  • Chapter
Brain, Behaviour, and Iron in the Infant Diet

Abstract

Iron is an integral component or an essential cofactor of several enzymes such as aconitase, catalase, cytochrome C, cytochrome C reductase, cytochrome C oxidase, formiminotransferase, monoamine oxidase, myeloperoxidase, peroxidase, ribonucleotidyl reductase, succinic dehydrogenase, tyrosine hydroxylase, tryptophan pyrrolase and xanthine oxidase [1]. These enzymes are involved in a number of important pathways such as DNA synthesis, mitochondrial electron transport, catecholamine metabolism, neurotransmitter levels, and detoxification [1]. Iron is also involved in lipid metabolism. The multienzyme complex which catalyses the desaturation of stearoyl-CoA to yield the monounsaturated oleoyl-Coa (Δ 9-desaturase) contains not only cytochrome b5 but also a terminal desaturase enzyme which is a non-heure iron protein [2–4]. Thus, each desaturase enzyme complex contains two atoms of iron. Iron is also required for the production of polyunsaturated fatty acids [5]. Carnitine is necessary for the transport of long-chain fatty acids into the mitochondria for beta-oxidation. Its synthesis from trimethyl lysine involves two hydroxylases which require ferrous iron [6,7]. Hepatic levels of carnitine have been reported to be reduced in irondeficient rat pups compared to iron-supplemented controls [8]. Thus iron has an important role in various metabolic events related to lipids, such as oxidative degradation of fatty acids, synthesis of mono- and polyunsaturated fatty acids, plasmalogens and prostaglandins [9]. Although lipids play a key role in many health-related problems such as obesity, cancer and heart disease, investigations on the effects of iron deficiency on tissue lipid metabolism have been sparse.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Vyas D, Chandra RK (1984) Functional implications of iron deficiency. In Stekel A (ed): Iron nutrition in infancy and childhood. Raven Press, New York, pp 45–59

    Google Scholar 

  2. Shimakata T, Mihara K, Sato R (1972) Reconstitution of hepatic microsomal stearoyl coenzyme. A desaturase system from solubilized components. J Biochem (Tokyo) 72: 1163–1174

    CAS  Google Scholar 

  3. Holloway PW, Katz JT (1972) A requirement for cytochrome b5 in microsomal stearyl coenzyme A desaturation. Biochemistry 11: 3689–3696

    Article  PubMed  CAS  Google Scholar 

  4. Strittmatter P, Spatz L, Corcoran D, Rogers MJ, Setlow B, Redline R (1974) Purification and properties of rat liver microsomal stearyl coenzyme desaturase. Proc Natl Acad Sci USA 71: 4565–4569

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  5. Okayasu T, Nagao M, Ishibashi T, Imai Y (1981) Purification and partial characterization of linoleoyl-CoA desaturase from rat liver microsomes. Arch Biochem Biophys 206: 21–28

    Article  PubMed  CAS  Google Scholar 

  6. Lindstedt G (1967) Hydroxylation of γ-butyrobetaine to carnitine in rat liver. Biochemistry 5: 1271–1281

    Article  Google Scholar 

  7. Hulse JD, Ellis SE, Henderson LM (1978) Carnitine biosynthesis. ß-Hydroxylation of trimethyl lysine by an α-ketoglutarate-dependent mitochondrial dioxygenase. J Biol Chem 253: 1654–1659

    PubMed  CAS  Google Scholar 

  8. Bartholmey SJ, Sherman AR (1985) Carnitine levels in iron-deficient pups. J Nutr 115: 138–145

    PubMed  CAS  Google Scholar 

  9. Rao GA, Larkin EC (1984) Role of dietary iron in lipid metabolism. Nutr Res 4: 145–151

    Article  CAS  Google Scholar 

  10. Dhopeshwarker GA (1983) Growth characteristics of the brain. Nutrition and brain development. Plenum Press, New York, pp 13–22

    Chapter  Google Scholar 

  11. Boggs TR, Morris RS (1909) Experimental lipemia in rabbits. J Exp Med 11: 553–560

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  12. Horiuchi Y (1920) Studies on blood fat. II Lipemia in acute anemia. J Biol Chem 44: 363–379

    CAS  Google Scholar 

  13. Bloor WR (1921) Lipemia. J Biol Chem 49: 201–227

    CAS  Google Scholar 

  14. Fishberg EH, Fishberg AM (1928) The mechanism of the lipemia of bleeding. Proc Soc Exp Biol Med 25: 296–299

    Article  Google Scholar 

  15. Johansen AH (1930) Lipemia in hemorrhagic anemia in rabbits. J Biol Chem 88: 669–673

    Google Scholar 

  16. Spitzer JJ, Spitzer JA (1955) Hemorrhagic lipemia: a derangement of fat metabolism. J Lab Clin Med 46: 461–470

    PubMed  CAS  Google Scholar 

  17. Amine EK, Hegsted DM (1971) Iron deficiency lipemia in the rat and chick. J Nutr 101: 1575–1582

    PubMed  CAS  Google Scholar 

  18. Lewis M, Iammarino M (1971) Lipernia in rodent iron-deficiency anemia. J Lab Clin Med 78: 546–554

    PubMed  CAS  Google Scholar 

  19. Guthrie HA, Froozani HA, Wolinsky I (1974) Hyperlipidemia in offspring of iron deficient rats. J Nutr 104: 1273–1278

    PubMed  CAS  Google Scholar 

  20. Sherman AR, Guthrie HA, Wolinsky I (1977) Interrelationships between dietary iron and tissue zinc and copper levels and serum lipids in rats. Proc Soc Exp Biol Med 156: 396–401

    Article  PubMed  CAS  Google Scholar 

  21. Sherman AR, Guthrie HA, Wolinsky I, Zulak IM (1978) Iron deficiency hyperlipidemia in 18-day-old rat pups: effects of milk lipids, lipoprotein lipase and triglyceride synthesis. J Nutr 108: 152–162

    PubMed  CAS  Google Scholar 

  22. Sherman AR (1979) Serum lipids in suckling and post-weanling iron-deficient rats. Lipids 14: 888–892

    Article  PubMed  CAS  Google Scholar 

  23. Rothenbacher H, Sherman AR (1980) Target organ pathology in iron deficient suckling rats. J Nutr 110: 1648–1654

    PubMed  CAS  Google Scholar 

  24. Sherman AR (1978) Lipogenesis in iron deficient adult rats. Lipids 13: 473–478

    Article  PubMed  CAS  Google Scholar 

  25. Rao GA, Crane RT, Larkin EC (1983) Reduced plasma lecithin cholesterol acyl transferase activity in rats fed iron deficient diets. Lipids 18: 673–676

    Article  PubMed  CAS  Google Scholar 

  26. Sherman AR, Bartholmey SJ, Perkins EG (1982) Fatty acid patterns in iron deficient maternal and neonatal rats. Lipids 17: 639–643

    Article  PubMed  CAS  Google Scholar 

  27. Bloor WR, MacPherson DJ (1917) Blood lipids in anemia. J Biol Chem 31: 79–95

    CAS  Google Scholar 

  28. Erickson BN, Williams HH, Hummel FC, Lee P, Macy IG (1937) The lipids and mineral distribution of the serum and erythrocytes in the hemolytic and hypochromic anemias of childhood. J Biol Chem 18: 569–597

    Google Scholar 

  29. Skrede S, Seip M (1979) Seum lipoproteins in children with anemia. Scand J Haemato 123: 232–238

    Google Scholar 

  30. Ohira Y, Edgerton R, Gardner CW, Senewiratne B (1980) Serum lipid levels in iron deficiency anemia and effects of various treatments. J Nutr Sci Vitamino 126: 375–379

    Article  Google Scholar 

  31. Fujii T, Shimizu H (1973) Investigations on serum lipid components and serum vitamin E in iron deficiency anemia. J Nutr Sci Vitaminol 19: 23–28

    Article  PubMed  CAS  Google Scholar 

  32. Rifkind BM, Gale M (1967) Hypolipidemia in anemia. Lancet ii: 640–642

    Article  Google Scholar 

  33. Rifkind BM, Gale M (1968) Hypolipidemia in anemia. Am Heart J 76: 849

    Article  PubMed  CAS  Google Scholar 

  34. Hashmi JA, Afroz N (1969) Hypolipidemia in anemia. Am Heart J 78: 840

    Article  Google Scholar 

  35. Bottiger LE, Carlson LA (1972) Relation between serum cholesterol and triglyceride concentration and haemoglobin values in non-anemic healthy persons. Brit Med J 3: 731–733

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  36. Rao GA, Larkin EC (1988) Hypertriglyceridemia in iron-deficient neonatal rats: possible origin of fatty acids from milk fat. Biochem Arch 4: 125–130

    CAS  Google Scholar 

  37. Smith S, Abraham S (1975) The composition and biosynthesis of milk fat. Adv Lipid Res 13: 195–239

    PubMed  CAS  Google Scholar 

  38. Dallman PR, Goodman JR (1971) The effects of iron deficiency on the hepatocyte: a biochemical and ultrastructural study. J Cell Biol. 48: 79–90

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  39. Jain SK, Yip R, Pramanik AK, Dallman PR, Shohet SB (1982) Reduced plasma lecithin cholesterol acyl transferase activity in iron deficient rats: its possible role in the lipemia of iron deficiency. J Nutr 112: 1230–1232

    PubMed  CAS  Google Scholar 

  40. Rao GA, Jarratt BA, Larkin EC (1985) Decreased lecithin cholesterol acyl transferase activity in the plasma of rats due to iron deficiency. Biochem Arch 1: 191–197

    CAS  Google Scholar 

  41. Rao GA, Larkin EC (1984) Alcoholic fatty liver: a nutritional problem of carbohydrate deprivation and concomitant ethanol ingestion. Nutr Res 4: 903–912

    Article  CAS  Google Scholar 

  42. Takada A, Porta EA, Hartroft WS (1967) Regression of dietary cirrhosis in rats fed alcohol and a “super diet”. Am J Clin Nutr 20: 213–225

    PubMed  CAS  Google Scholar 

  43. Yu GSM, Larkin EC, Rao GA (1989) Progressive development of fatty liver and changes in hepatocyte ultrastructure in iron-deficient neonatal rats. Biochem Arch 5: 91–99

    CAS  Google Scholar 

  44. Rao GA, Larkin EC (1989) Changes in liver lipids of iron-deficient rat pups during suckling period. Biochem Arch 5: 125–132

    Google Scholar 

  45. Rao GA, Manix M, Larkin EC (1980) Reduction of essential fatty acid deficiency in rats fed a low iron fat free diet. Lipids 15: 55–60

    Article  PubMed  CAS  Google Scholar 

  46. Rao GA, Crane RT, Larkin EC (1983) Reduction of hepatic stearoyl-CoA desataurase activity in rats fed iron-deficient diets. Lipids 18: 573–575

    Article  PubMed  CAS  Google Scholar 

  47. Cuzner ML, Davison AN, Gregson NA (1966) Turnover of brain mitochondrial membrane lipids. Biochem J 101: 618

    PubMed  CAS  PubMed Central  Google Scholar 

  48. Cuzner ML, Davison AN (1968) The lipid composition of rat brain myelin and subeellular fractions during development. Biochem J 106: 29–34

    PubMed  CAS  PubMed Central  Google Scholar 

  49. Davison AN (1969) The biochemistry of myelinogenesis. Neuropat Pol 3: 251–254

    Google Scholar 

  50. Davison AN (1969) Biochemistry of the myelin sheath. Ann Rev Sci Basis Med 220–235

    Google Scholar 

  51. Davison AN, Dobbing J (1966) Myelination as a vulnerable period in brain development. Br Med Bull 22: 44–44

    Google Scholar 

  52. Dobbing J (1964) The influence of early nutrition on the development and myelination of the brain. Proc R Soc Lond (Biol) 159: 503–509

    Article  CAS  Google Scholar 

  53. Dobbing J (1968) Vulnerable periods in developing brain. In: Davison AN, Dobbing J. (eds) Applied neurochemistry. Blackwell, Oxford, pp 287–316

    Google Scholar 

  54. Dalal KB, Valcana T, Timiras S, Einstein ER (1971) Regulatory role of thyroxine on myelinogenesis in the developing rat. Neurobiol 1: 211–224

    CAS  Google Scholar 

  55. Kurtz DJ, Kanfer JN (1973) Composition of myelin lipids and synthesis of 3-ketodihydrosphingosine in the vitamin B6-deficient developing rat. J Neurochem 20: 963–968

    Article  PubMed  CAS  Google Scholar 

  56. Zimmerman AW, Matthieu JM, Quarles RH, Brady RO, Hsu JM (1976) Hypomyelination in copper-deficient rats. Arch Neurol 33: 111–119

    Article  PubMed  CAS  Google Scholar 

  57. Yu GSM, Steinkirchner TM, Rao GA, Larkin EC (1986) Effect of prenatal iron deficiency on myelination in rat pups. Am J Pathol 125: 620–624

    PubMed  CAS  PubMed Central  Google Scholar 

  58. Srere PA, Chaikoff IL, Treitman SS, Burstein LS (1950) The extrahepatic synthesis of cholesterol. J Biol Chem 182: 629–634

    CAS  Google Scholar 

  59. Davison AN, Dobbing J, Morgan RS, Payling Wright G (1959) Metabolism of myelin: the persistence of [4–14 C] cholesterol in the mammalian central nervous system. Lancet i: 658–660

    Article  Google Scholar 

  60. Carey EM (1982) The biochemistry of fetal brain development and myelination. In: Jones CT (ed) The biochemical development of the fetus and neonate. Elsevier, Amsterdam, pp 287–336

    Google Scholar 

  61. Cook HW, Spence MW (1973) Formation of monoenoic fatty acids by desaturation in rat brain homogenate. Some properties of the enzyme system of 10-day old brain. J Biol Chem 248: 1786–1793

    PubMed  CAS  Google Scholar 

  62. Cook HW, Spence MW (1973) Formation of monoenoic fatty acids by desaturation in rat brain homogenate. Effects of age, fasting and refeeding and comparison with the liver enzyme. J Biol Chem 248: 1793–1796

    PubMed  CAS  Google Scholar 

  63. Cook HW (1979) Differential alteration of Δ9- and Δ6-desaturation of fatty acids in brain preparations in vitro. Lipids 16: 763–767

    Article  Google Scholar 

  64. Cook HW, Spence MW (1974) Biosynthesis of fatty acids in vitro by homogenate of developing rat brain: desaturation and chain-elongation. Biochim Biophys Acta 369: 129–141

    Article  PubMed  CAS  Google Scholar 

  65. Sanders TAB, Naismith DJ (1979) Synthesis of arachidonic acid by fetal rat brain. Proc Nutr Soc 38: 94A

    Google Scholar 

  66. Pullarkat RK, Maddow J, Reha H (1976) Effect of early postnatal dietary sterculate on the fatty acid composition of rat liver and brain lipids. Lipids 11: 802–807

    Article  CAS  Google Scholar 

  67. Larkin EC, Jarratt BA, Rao GA (1986) Reduction of relative levels of nervonic to lignoceric acid in the brain of rat pups due to iron deficiency. Nutr Res 6: 309–317

    Article  CAS  Google Scholar 

  68. Baumann NA, Jacque CM, Pollet SA, Harpin ML (1968) Fatty acid and lipid composition of the brain of a myelin deficient mutant, the “quaking” mouse. Europ J Biochem 4: 340–344

    Article  PubMed  CAS  Google Scholar 

  69. Nussbaum JL, Neskovic N, Mandel P (1971) Fatty acid composition of phospholipids and glycolipids in jimpy mouse brain. J Neurochem 18: 1529–1543

    Article  PubMed  CAS  Google Scholar 

  70. Joseph KC, Druse MJ, Newell LR, Hogan EL (1972) Fatty acid composition of cerebrosides, sulphatides and ceramides in murine leucodystrophy: quaking mutant. J Neurochem 19: 307–312

    Article  PubMed  CAS  Google Scholar 

  71. Folch J, Lees M, Sloane-Stanley GS (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226: 497–509

    PubMed  CAS  Google Scholar 

  72. Dittmer JC, Wells MA (1969) Quantitative and qualitative analysis of lipids and lipid components. Methods Enzymo 114: 482–530

    Article  Google Scholar 

  73. Rudel LL, Morris MD (1973) Determination of cholesterol using O-phthalaldehyde. J Lipid Res 14: 364–366

    PubMed  CAS  Google Scholar 

  74. Norton WT, Poduslo SE (1973) Myelination in rat brain: method of myelin isolation. J Neurochem 21: 749–757

    Article  PubMed  CAS  Google Scholar 

  75. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951). Protein measurement with folin phenol reagent. J Biol Chem 193: 265–275

    PubMed  CAS  Google Scholar 

  76. Ramsay RB, Nicholas HJ (1972) Brain lipids. Adv Lipid Res 10: 143–232

    Google Scholar 

  77. Yoshioka T, Roux JF (1972) In vitro metabolism of palmitic acid in human fetal tissue. Pediatr Res 6: 675–681

    Article  PubMed  CAS  Google Scholar 

  78. Spitzer JJ (1975) Application of tracers in studying free fatty acid metabolism of various organs in vivo. Fed Proc 36: 2242–2245

    Google Scholar 

  79. Warshaw JB, Terry ML (1976) Cellular energy metabolism during fetal development. VI, Fatty acid oxidation by developing brain. Dev Bio 152: 161–166

    Article  Google Scholar 

  80. Cantrill RC, Carey EM (1975) Changes in the activities of de novo fatty acid synthesis and palmitoyl-CoA synthetase in relation to myelination in rabbit brain. Biochim Biophys Acta 380: 165–175

    Article  PubMed  CAS  Google Scholar 

  81. Gross I, Warshaw JB (1974) Fatty acid synthesis in developing brain. Biol Neonate 25: 365–375

    Article  PubMed  CAS  Google Scholar 

  82. Reijnierse GLA, Veldstra H, Vandenberg CJ (1975) Short-chain fatty acid synthesis in brain. Subcellular localization and changes during development. Biochem J 152: 477–484

    PubMed  CAS  PubMed Central  Google Scholar 

  83. Cunnane SC, MacAdoo KR (1987) Iron intake influences essential fatty acid and lipid composition of rat plasma and erythrocytes. J Nutr 117: 1514–1519

    PubMed  CAS  Google Scholar 

  84. Dobbing J (1987) Early nutrition and later achievement. Academic Press, London.

    Google Scholar 

  85. Dobbing J, Widdowson EM (1965) The effect of undernutrition and subsequent rehabilitation on myelination of rat brain as measured by its composition. Brain 88: 357–366

    Article  PubMed  CAS  Google Scholar 

  86. Dobbing J (1966) Effect of undernutrition on myelination in central nervous system. Biol Neonat 9: 132–147

    Article  CAS  Google Scholar 

  87. Davison AN (1968) The influence of nutritional disorder in the lipid composition of the central nervous system. Proc Nutr Soc 27: 83–85

    Article  PubMed  CAS  Google Scholar 

  88. Pollitt E, Leibel RL (1976) Iron deficiency and behavior. J Pediatr 88: 372–381

    Article  PubMed  CAS  Google Scholar 

  89. Pollitt E, Saco-Pollitt C, Leibel RL, Viteri FE (1986) Iron deficiency and behavioral development in infants and preschool children. Am J Clin Nutr 43: 555–565

    PubMed  CAS  Google Scholar 

  90. Soemantri AG, Pollitt E, Kim I (1985) Iron deficiency anemia and educational achievement. Am J Clin Nutr 42: 1221–1228

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. Edward C. Larkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Ananda Rao
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Child Health, University of Manchester, Oxford Road, M13 9PT, Manchester, UK

    John Dobbing DSc, FRCP, FRCPath (Emeritus Professor of Child Growth and Development) (Emeritus Professor of Child Growth and Development)

Rights and permissions

Reprints and permissions

Copyright information

© 1990 Springer-Verlag London

About this chapter

Cite this chapter

Larkin, E.C., Rao, G.A. (1990). Importance of Fetal and Neonatal Iron: Adequacy for Normal Development of Central Nervous System. In: Dobbing, J. (eds) Brain, Behaviour, and Iron in the Infant Diet. Springer, London. https://doi.org/10.1007/978-1-4471-1766-7_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-1766-7_5

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-1768-1

  • Online ISBN: 978-1-4471-1766-7

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation