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 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 (Fe 3+ )

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(Fe 2+ ) – Absorbed form Ferric (Fe 3+ ) – 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

8 Iron Links

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%)