Iron Metabolism

Iron  metabolism

Curriculum

•      List the iron containing haeme and non-haeme  proteins  and describe their functions

•      Describe the intestinal absorption of iron and distribution kinetics in the body

•      Describe the process of haeme biosynthesis and catabolism

•      Describe iron deficiency anaemia and acute intermittent porphyria

•      Describe the diagnostic test for iron states (serum iron, serum iron binding capacity, serum ferritin)

•      Describe and classify porphyria

•      Describe the causes, diagnosis and management of porphyria

Heme containing proteins & enzymes

Hemoglobin: transport of oxygen in blood

Myoglobin: storage of oxygen in muscle

Cytochrome c: involvement in oxygen transport chain

Catalase/Peroxidase: antioxidant enzymes that protect cells from reactive oxygen species(ROS)

Tryptophan pyrrolase: oxidation of tryptophan

Cytochrome P 450 : for hydroxylation of xenobiotics

Non-heme, iron-containing proteins

Transferrin/lactoferrin : proteins responsible for iron transport

Ribonucleotide reductase: enzyme involvedin DNA synthesis

Ferritin :protein used for intracellular iron storage

NADH dehyrogenase/succinate dehydrogenase : enzymes involved in mitochondrial  energy  production

Transferrin,ferritin and hemosiderin

•      Transferrin :

B1 globulin synthesized in liver: transports 2 moles of ferric ion per mole of transferrin

•      Ferritin : contains  23% of iron and consists of apoferritin which surrounds in a micellar form

•      3000-4500 ferric atoms.

•      Hemosiderin: ill-defined molecule.Detected in histology by Prussian blue stain

 IRON IN MUCOSAL CELL

•      Table 50–3. Distribution of iron in a 70-kg

•      adult male.

•      Transferrin 3–4 mg

•      Hemoglobin in red blood cells 2500 mg

•      In myoglobin and various enzymes 300 mg

•      In stores (ferritin and hemosiderin) 1000 mg

•      Absorption 1 mg/d

•      Losses 1 mg/d

In an adult female of similar weight, the amount in stores would

generally be less (100–400 mg) and the losses would be greater

(1.5–2 mg/d).

 Hemoglobin

      Heme + globin

Tetrapyrrole ring with iron in the centre   in the form of ferrous ion      

       

Catabolism 

•      Iron deficiency anemia

•      Anemia: reduction of oxygen transport capacity of blood due to reduction of total red cell mass and hemoglobin level

•      Microcytosis and hypochromia

•      Iron is a micronutrient and less than 100mg/day is needed.

•      investigations

•       serum iron

•      TIBC

•      TIBC- serum iron = UIBC

•      Ferritin

•      Iron is carried in the plasma bound to protein transferrin

•      Excess iron in form of ferric chloride is added to serum and . Any iron that does not bind to transferrin is removed by excess magnesium carbonate.The iron  conc  of  iron-saturated serum is measured.

•      TIBC- serum iron= UIBC

•      Ferritin is found both in blood and tissue

•      It is acute phase protein and is nonspecific

•      Rises in malignancies too

•      porphyrias

 inborn error of metabolism due to mutation in genes responsible for enzymes involved in synthesis of Hb

•      Precipitated by anaesthetic, barbiturates, griseofulvin, alcohol by inducing P 450 which uses of heme and derepresses ALA  synthase

•      Prototype of werewolves/ vampires

•      Psychiatrist 

•      Hepatologist

•      Dermatologist

•      diagnosis

•      Acute  intermittent porphyria  :Urinary PBG

•      D/D of acute abdomen

•      Ehrlich’s aldehyde test

•      management

•      On biochemical basis

•      Skin  Beta carotene

•      Avoid drugs and alcohol and anesthesia

•      Hematin hydroxide  causes repression of  ALA Synthase and abundant carbohydrate diet will  repress