1. MLAB 2401: Clinical Chemistry Keri Brophy-Martinez
Overview :
Iron, Porphyrins, and Hemoglobin

2. 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

3. 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 mg per day.

4. Forms of Iron Ferrous(Fe2+) Ferric (Fe3+) Absorbed form
Transport and storage form
Delivered to cells having receptor sites
Gut mucosal cells
Liver cells
RE system cells

5. 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 (Fe3+)

6. 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

7. 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

8. Putting it all together….

9. Functions of Iron Essential element of heme, myoglobin, and hemoglobin
Component of some enzymes involved in cellular oxidative mechanisms

10. 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.

11. Hemosiderin Another storage form of iron
Partially deproteinized ferritin
Insoluble
Found in cells of liver, spleen, and bone marrow
Slowly releases iron

12. 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

13. Porphyrins General structure Cyclic compounds called tetrapyrroles
Linked by four pyrrole rings bonded by methene bridges
Able to bind metals due to nitrogen atoms

14. Porphyrins Color Fluorescence Purple
Absorb electromagnetic radiation at 400 nm
Fluorescence
Produce an orange-red fluorescence around the nm range

15. Porphyrin Synthesis & Control
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

16. Porphyrins: Ones to keep an Eye on
Uroporphyrin: URO
Water soluble
Heme precursor
Found in urine
Coproporphyrin: COPRO
Found in urine and feces
Protoporphyrin: PROTO
Water insoluble
Found in feces

17. Porphyrinogens Reduced form of porphyrins Functional precursor of heme
Difficult to measure due to instability and colorlessness

18. Steps to Heme Synthesis

19. 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

20. 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

21. 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%)

22. References
transport-iron-ore-in-career.html
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 .