MLAB 2401: Clinical Chemistry Keri Brophy-Martinez Overview : Iron, Porphyrins, and Hemoglobin
MLAB 2401: Clinical Chemistry
Keri Brophy-Martinez
Overview :
Iron, Porphyrins, and Hemoglobin
Overview of Iron
Essential mineral to most living organisms
Most abundant trace element
Where is it found?
◦ Majority is found in red blood cells
◦ Myoglobin: oxygen-carrying molecule of muscle
◦ Tissue: bound to enzymes
◦ Bone marrow, spleen, liver: storage forms
Where does iron come from?
• Two types
• Heme
• meats, especially organ meats
• Non-Heme
• spinach, beets, beans, almonds, bran flakes..etc
• Typical dietary intake is
10-20 mg per day.
Forms of Iron
•
•
Ferrous(Fe 2+ )
– Absorbed form
Ferric (Fe 3+ )
– Transport and storage form
– Delivered to cells having receptor sites
• Gut mucosal cells
• Liver cells
• RE system cells
Regulation
Regulated by absorption of iron NOT excretion
Dietary sources
Absorption
◦ Must be in ferrous state (Fe ++ )
◦ Occurs in the stomach/small intestines
Iron “stores”
◦ Iron is recycled when RBCs are broken down
◦ 25% stored in liver, spleen and bone marrow as
ferritin or (Fe 3+ )
Iron Absorption
~10% absorbed in duodenum and jejunem
Absorption is tightly regulated
Absorption controls total body iron content
Once absorbed, there is no mechanism to excrete excess iron
Iron Transport
Absorbed iron is transported in the blood bound to transferrin
Approximately 1% of total body iron is bound to transferrin
Transferrin releases iron to bone marrow to use in hemoglobin
Putting it all together….
Functions of Iron
Essential element of heme, myoglobin, and hemoglobin
Component of some enzymes involved in cellular oxidative mechanisms
Ferritin
Soluble molecule
Protein shell surrounding an iron core
Can convert iron inside the core into ferric iron for distribution to body cells
Provides a reserve or iron for formation of hemoglobin etc.
Hemosiderin
Another storage form of iron
Partially deproteinized ferritin
Insoluble
Found in cells of liver, spleen, and bone marrow
Slowly releases iron
Transport Proteins
Apotransferrin
◦ Protein in the plasma that moves iron from one organ to another
Transferrin
◦ Glycoprotein formed in the liver
◦ Picks up free, ferric form iron from GI tract and delivers it to specific receptor sites
Porphyrins
General structure
◦ Cyclic compounds called tetrapyrroles
◦ Linked by four pyrrole rings bonded by methene bridges
◦ Able to bind metals due to nitrogen atoms
Porphyrins
Color
◦ Purple
◦ Absorb electromagnetic radiation at 400 nm
Fluorescence
◦ Produce an orange-red fluorescence around the 500-650 nm range
Porphyrin Synthesis & Control
Synthesis
◦ Bone marrow and liver are the main site
◦ Synthesis occurs in mitochrondria and cytoplasm of cell
Control
◦ Enzyme: δ -aminolevulinic acid (ALA)
Found in liver
◦ Negative Feedback Mechanism
◦ Rate of heme syntheis is flexible and can change rapidly in response to external stimuli
Porphyrins: Ones to keep an Eye on
Uroporphyrin: URO
◦ Water soluble
◦ Heme precursor
◦ Found in urine
Coproporphyrin: COPRO
◦ Water soluble
◦ Heme precursor
◦ Found in urine and feces
Protoporphyrin: PROTO
◦ Water insoluble
◦ Heme precursor
◦ Found in feces
Porphyrinogens
Reduced form of porphyrins
Functional precursor of heme
Difficult to measure due to instability and colorlessness
Steps to Heme Synthesis
Myoglobin
Heme protein found in skeletal and cardiac muscle
Main function is to transport oxygen from the muscle cell membrane to the mitochondria
Serves as an extra reserve of oxygen to help exercising muscle maintain activity longer
Used to diagnose acute myocardial infarction
Lead
Found in the environment and in paint
Considered a toxin
◦ Interferes with hem synthesis
Exposure primarily respiratory or gastrointestinal
Half-life in whole blood= 2-3 weeks
◦ Half-life= the time required by the body, tissue or organ to metabolize or inactivate half the amount of substance taken in
Lead
Absorption
◦ Depends on age, nutritional status and other substances that are present
Transport
◦ Once in the blood, 94% transferred to RBC bound to hgb
◦ Once it reaches its half-life, lead is distributed to soft tissues, such as kidneys, liver and brain. Final storage is in soft tissue(5%) and bone (95%)
Excretion
◦ Urine (76%)
◦ Feces (16%)
◦ Other (8%)
References
http://www.123rf.com/photo_5547046_the-big-trucktransport-iron-ore-in-career.html
http://www.cdc.gov/ncbddd/hemochromatosis/training/p athophysiology/iron_cycle_popup.htm
Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical Chemistry:
Techniques, principles, Correlations. Baltimore: Wolters
Kluwer Lippincott Williams & Wilkins.
Sunheimer, R., & Graves, L. (2010). Clinical Laboratory
Chemistry. Upper Saddle River: Pearson .
