Lecture Five - Iron metabolism FINAL.pptx

01/31/2025 2
Lecture Overview
• In this lecture:
– What are the importance of Iron in the body?
– What are the sources of iron in the diet?
– How much do we need everyday?
– What are the biochemical functions of iron in the body?
– How iron is absorbed, transported and stored?
– How iron is metabolized?
– How is iron metabolism regulated in the body?

01/31/2025 3
Lecture Objectives
• At the end of this lecture, the student should be able to:
– Explain the importance of iron in the body
– State some sources of iron in the body
– State the required daily allowance (RDA) of iron for humans
– Describe the mechanisms by which iron is absorbed,
transported and stored in the human body
– Describe how iron is metabolized in the body
– Describe the mechanism by which iron metabolism is regulated

01/31/2025 4
Introduction
• Iron is one of the most essential trace element; total body
iron content is 3 to 5 g
• Iron is present in almost all cells; 75% present in blood, the
rest is in liver, bone marrow & muscles
• Heme is the most predominant iron-containing substance
• It is a constituent of proteins/enzymes (hemoproteins) –
Hemoglobin, myoglobin, cytochromes, catalase, xanthine
oxidase, tryptophan pyrrolase, peroxidase

01/31/2025 5
Introduction
• Non-heme proteins that bind iron are Iron-sulphur proteins –
succinate dehydrogenase, aconitase, NADH dehydrogenase,
cytochrome C reductase (Coenzyme Q)
• Transport protein that binds iron – transferrin; Storage protein
(stores iron in cells) – ferritin
• Sources:
– liver, red meat (beef, lamb), egg yolk, green leafy vegetables,
dates, whole grains and cereals
• Milk is a very poor source of iron, containing less than 0.1
mg/100 ml; also interferes with iron absorption

01/31/2025 6
Distribution of Iron in a 70-kg Adult Male

01/31/2025 7
Introduction
• RDA:
– Adult man & postmenopausal women – 8 mg
– Premenopausal women – 18 mg
– Adolescents 14 – 18 years) – 11 mg (boys); 15 mg (girls)
– Pregnant women – 27 mg
– Lactation – 9 – 10 mg
• ***Women require greater amount than men due to physiological loss
during menstruation
• ***Pregnant women also need greater amounts because of the rapid
growth of the foetus requiring extra blood circulation during pregnancy

01/31/2025 8
Biochemical functions of Iron
• Iron is a component of several functionally important
molecules.
• Iron is required for the synthesis of hemoglobin, myoglobin,
cytochromes, catalase and peroxidase
• Cytochromes & certain non-heme proteins are necessary for
ETC & oxidative phosporylation.
• Peroxidase, the lysosomal enzyme, is required for
phagocytosis & killing of bacteria

01/31/2025 9
Biochemical functions of Iron
• Iron is also essential for the synthesis of non heme iron (NHI)
compounds like, succinate dehydrogenase, iron-sulfur
proteins of flavoproteins, and NADH dehydrogenase
• Iron helps mainly in the transport, storage and utilization of
oxygen.
• Iron is associated with effective immuno-competence of
body.

01/31/2025 10
Metabolism of Iron - Absorption
• Iron is referred to as one way substance, because it is absorbed
and excreted from small intestine.
• Iron is absorbed from upper small intestine; absorbed in three
forms: (1) ferrous iron (mainly) (2) ferric iron (3) heme iron (most
easily absorbed form)
• Ferric ions (Fe3+
) are insoluble and must be reduced to the more
soluble ferrous (Fe2+
) form which is more readily absorbed
• This is catalyzed by duodenal cytochrome B (DcytB) on the brush
border of enterocytes; low gastric pH allows this reaction

01/31/2025 11
Metabolism of Iron – absorption
• Ferrous iron is then transported across the apical membrane
of enterocytes by Divalent metal cation transporter 1
(DMT1); Unabsorbed iron is excreted
• Heme iron is absorbed by the heme carrier protein 1 (HCP1)
across the apical membrane of enterocytes
• The heme iron is then degraded by heme oxygenase with the
release of the ferrous form of iron

01/31/2025 12
• After absorption, iron can be stored temporarily in mucosal
cells; apoferritin oxidizes ferrous iron to ferric iron, binds and
stores it as ferritin
• Ferritin is a hollow, spherical protein consisting of 24 subunits
that potentiate the storage and regulation of iron levels within
the body
• Iron is stored in liver, spleen & bone marrow as ferritin
• Ferritin level in plasma is elevated in iron over load in
inflammatory diseases
Metabolism of Iron – Storage

01/31/2025 13
• Hemosiderin – another iron storage protein, which can hold
about 35% of iron by weight.
• It is a complex of iron with phosphate and hydroxide;
• Hemosiderin is derived chiefly from the breakdown of
erythrocytes; accumulates when iron levels are increased
(ferritin stores are exceeded)
Metabolism of Iron – Storage

01/31/2025 14
Factors affecting Iron Absorption - Increase
• Ascorbic acid, cysteine (amino acids), sugars and gastric
secretions favor the reduction of ferric form of iron to ferrous
form
• Cystatin C & HCl also favor the reduction of ferric form of iron
to ferrous more absorbable form
• Iron absorption is increased to 2 – 10 times that of normal in
iron deficiency state and reduced in iron overload

01/31/2025 15
Factors affecting Iron Absorption - Decrease
• Iron absorption is enhanced by low pH of gastric acid in
proximal duodenum
• Phytates and polyphenols in the food, oxalates, tannates and
antacids containing calcium decrease iron absorption
• Achlorhydria – the absence of HCl in gastric secretions results
in impaired conversion of ferric form of iron to ferrous form of
iron.
• Iron absorption is deceased in the presence of gastrointestinal
diseases such as celiac and Crohn’s diseases

01/31/2025 16
Metabolism of Iron – Transport
• From the mucosal cells, iron may be transported across the
basolateral membrane of enterocytes into the circulation
• The transmembrane protein, ferroportin is the only efflux
route of cellular iron
• Iron enters plasma in the Fe2+
form and must be oxidized to
Fe3+
form to be bound to transferrin, the transport protein
• Ceruloplasmin in the plasma and hephaestin on the
basolateral membrane of the enterocyte, catalyze the
oxidation and binding of ferrous iron to transferrin

01/31/2025 17
• Both ceruloplasmin and hephaestin are copper-containing
enzymes
• The principal role of transferrin is to chelate iron to be
rendered soluble, prevent the formation of reactive oxygen
species, and facilitate its transport into cells
• Transferrin is a glycoprotein synthesized in liver; one molecule
of transferrin can transport 2 ferric atoms and the half-life of
transferrin is 7- 10 days
• Normal plasma level of transferrin is 250 mg/dl.

01/31/2025 18
• Total iron binding capacity (TIBC) of transferrin is 250-450
µg/dl;
• In iron deficiency anemia, serum iron level is decreased and
TIBC is increased.

01/31/2025 19
• The normal Iron excretion is about 1mg/day.
• The major excretory pathway is through intestine as
unabsorbed iron and from rapid turnover and excretion of
enterocytes
• It can also be lost in sweat, menstruation, and shedding of
hair and skin cells
• Iron is not excreted in urine, but in nephrotic syndrome, loss
of transferrin may lead to increased loss of iron in urine.
Metabolism of Iron – Excretion

01/31/2025 20
• Iron metabolism is regulated by the peptide hormone,
hepcidin; it controls how much iron is available for essential
functions
• It has molecular weight of 25 kda and a highly folded structure
• Present in inactive form, prohepcidin (60 aa) and its active
form is hepicidin (25 aa)
• It regulates iron metabolism by binding and forming a
complex with iron transporter ferroportin which is degraded
in lysosomes
Regulation of Iron Metabolism

01/31/2025 21
• This locks up iron in cells (mainly enterocytes, hepatocytes
and macrophages)
• Increased expression of hepicidin leads to decreased iron
absorption and release
• Hepicidin mRNA expression is increased by erythropoetin,
hypoxia & inflammation
• Deficiency of hepcidin leads to hereditary hemochromatosis,
a condition characterized by deposition of iron directly in
tissues

22
• At low levels of hepicidin, iron exporting cells release abundant ferroportin into
plasma. At high levels, hepicidin binds to ferroportin retaining iron in the cells.

01/31/2025 23
• Iron deficiency & iron overload are the major disorders of iron
metabolism
• Iron deficiency causes a reduction in the rate of haemoglobin
synthesis & erythropoiesis; can result in iron deficiency
anemia
• Iron deficiency is caused by inadequate intake, impaired
absorption, chronic blood loss & increased demand.
• Iron deficiency anemia mostly occurs in growing children,
adolescent girls, pregnant & lactating women.
Disorders of Iron metabolism

01/31/2025 24
• Microcytic hypochromic anemia in which the size of the red
blood cells are smaller than normal and have much reduced
haemoglobin content.
• Weakness, fatigue, dizziness and palpitation,
• Nonspecific symptoms are nausea, anorexia, constipation,
and menstrual irregularities.
Clinical features

01/31/2025 25
• Haemosiderosis, haemochromatosis and iron poisoning are
conditions associated with iron over load.
• Haemosiderosis – accumulation of hemosiderin in liver &
other reticulo-endothelial system;
– an initial stage of iron over load and there is no significant tissue
destruction
• Haemochromatosis – a clinical condition in which iron is
directly deposited in the tissues (liver, spleen, pancreas & skin)
– It may be genetic (primary) or acquired (secondary)
Iron over load

01/31/2025 26
• Genetic (primary) hemochromatosis – hereditary disorder,
due to an unregulated increase in the intestinal absorption of
iron from normal diet.
• Various types depending on the gene affected (read on it)
• Iron is deposited as haemosiderin in liver, pancreas, heart,
skin, joints and other organs.
• After accumulation, excessive amounts of intracellular iron
lead to tissue injury and organ failure.
Haemochromatosis

01/31/2025 27
• Acquired (secondary) haemochromatosis – it is caused by:
• Excessive intake of iron – such as in unnecessary iron
supplements
• Increased hemolysis – such as occurring in hematologic
diseases such as blood cell cancers
• Repeated blood transfusions – in the case of some blood
disorders like thalassemia in which there is also excessive
absorption in the gastrointestinal tract
Haemochromatosis

01/31/2025 28
• Haemochromatosis are related to the involved organ systems as
follows:
• Liver: leading to cirrhosis
• Pancreas: leading to fibrotic damage to pancreas with diabetes
mellitus
• Skin: skin pigmentation, bronzed diabetes
• Endocrine organs: leading to hypothyroidism, testicular atrophy
• Joints: leading to arthritis
• Heart: leading to arrhythmia & heart failure
Clinical features

01/31/2025 29
• Acute overdose, mainly occurring in children may cause
severe or even fatal symptoms due to toxic effect of free iron
in plasma which may be life threatening.
• Symptoms – Nausea, vomiting, abdominal pain, diarrhoea.
Iron poisoning

Lecture Five - Iron metabolism FINAL.pptx

More Related Content

Similar to Lecture Five - Iron metabolism FINAL.pptx

Recently uploaded

Lecture Five - Iron metabolism FINAL.pptx