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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).
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MLAB 2401: Clinical ChemistryKeri 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 apoferritinto 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
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%)