MLAB 2401: Clinical Chemistry
Keri Brophy-Martinez
Chapter 5: Porphyrins and
Hemoglobin Overview
Overview of Iron
• Essential mineral to most living organisms
• Most abundant trace element
• 2-2.5 of the 3-5 grams of iron in our bodies is
found in hemoglobin (RBCs and RBC
precursors)
Where does iron come from?
• Dietary sources - meats,
especially organ meats,
spinach, beats,... etc.
Regulation
• 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+)
Functions of Iron
• Essential element of heme and hemoglobin
• Component of methemoglobin, myoglobin
and some enzymes
• Cellular oxidative mechanisms
Heme Sythesis Review
The addition of
ferrous iron
(Fe++)forms
heme
Forms of Iron
• Ferrous(Fe2+)
– Absorbed form
• Ferric (Fe3+)
–
–
–
–
Ferritin
Transport and storage form
Free ferric form is picked up in the plasma by protein transferrin
Delivered to cells having receptor sites
•
•
•
•
•
Gut mucosal cells
Liver cells
RE system cells
Once inside the cell, ferric iron attaches to protein apoferritin to form ferritin
Deficiency of apoferritin results in ferric iron deposits or hemosiderin, which is
insoluble
Iron Links
http://www.umm.edu/blood/aneiron.htm
http://www.ehendrick.org/healthy/000772.htm
http://www.nlm.nih.gov/medlineplus/ency/article/000584.htm
http://www.healthservices.gov.bc.ca/msp/protoguides/gps/ferritin.html
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Hemoglobin
• Structure, Synthesis, Degradation and Role
– Refer to Hematology notes for review
• Chapter 6 in McKenzie text
Porphyrins
• General structure
– Cyclic compounds called
tetrapyrroles
– Linked by four pyrrole
rings bonded by
methene bridges
Porphyrins
• Chemical intermediates in the synthesis of
hemoglobin, myoglobin and other respiratory
pigments (cytochromes)
• Clinical significance
– Presence indicates abnormal heme synthesis
Physical properties
• Color
– Coloration around 405 nm
– Usually red
• Fluorescence
– around 620 nm
– Reddish-pink color
• Chelation
– Arrangement of nitrogen atoms allows chelation of metal
atoms such as iron, that participate in oxidative
metabolism
Porphyrin Synthesis & Control
• Synthesis
– Bone marrow and liver are the main site
– Some steps of synthesis occur in mitochrondria and cytoplasm of cell
• Control
– Enzyme: δ-aminolevulinic acid (ALA)
• Found in liver
– Increases in hepatic heme decrease the production of ALA
– Decreases or depletions of heme result in ALA increased production
– Rate of heme syntheis is flexible and can change rapidily 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
Glycated hemoglobin
• Hemoglobin A 1c most stable
• Indicator of long-term glucose control
– Why?
• Reflects sustained average plasma glucose over the RBC
life span
– Correlates with risk of cardiovascular disease and
other vascular disorders
Myoglobin
• Heme protein found in skeletal and cardiac muscle
• Unable to release oxygen, except under low oxygen
tension
• 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, plays no known role in NORMAL human
physiology
• 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%)