MLAB 2401: Clinical MLAB 2401: Clinical ChemistryChemistryKeri Brophy-MartinezKeri Brophy-Martinez

Overview :Iron, Porphyrins, and Hemoglobin

Overview of IronOverview of IronEssential mineral to most living

organismsMost abundant trace elementWhere 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 Where does iron come from?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 IronForms of Iron• Ferrous(Fe2+)–Absorbed form

• Ferric (Fe3+)–Transport and storage form–Delivered to cells having receptor

sites• Gut mucosal cells• Liver cells• RE system cells

RegulationRegulationRegulated by absorption of iron

NOT excretionDietary sourcesAbsorption

◦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+)

Iron AbsorptionIron Absorption~10% absorbed in duodenum

and jejunemAbsorption is tightly regulated Absorption controls total body

iron contentOnce absorbed, there is no

mechanism to excrete excess iron

Iron TransportIron TransportAbsorbed 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….Putting it all together….

Functions of IronFunctions of IronEssential element of heme,

myoglobin, and hemoglobin

Component of some enzymes involved in cellular oxidative mechanisms

FerritinFerritinSoluble moleculeProtein 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.

HemosiderinHemosiderinAnother storage form of ironPartially deproteinized ferritinInsolubleFound in cells of liver, spleen,

and bone marrowSlowly releases iron

Transport ProteinsTransport 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

PorphyrinsPorphyrinsGeneral

structure◦ Cyclic compounds

called tetrapyrroles

◦ Linked by four pyrrole rings bonded by methene bridges

◦ Able to bind metals due to nitrogen atoms

PorphyrinsPorphyrinsColor

◦Purple◦Absorb electromagnetic radiation at

400 nmFluorescence

◦Produce an orange-red fluorescence around the 500-650 nm range

Porphyrin Synthesis & Porphyrin Synthesis & ControlControl 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 Porphyrins: Ones to keep an Eye onEye 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

PorphyrinogensPorphyrinogensReduced form of porphyrinsFunctional precursor of hemeDifficult to measure due to

instability and colorlessness

Steps to Heme SynthesisSteps to Heme Synthesis

MyoglobinMyoglobinHeme protein found in skeletal and

cardiac muscleMain 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

LeadLeadFound in the environment and in paintConsidered a toxin

◦ Interferes with hem synthesisExposure 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

LeadLead 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%)

ReferencesReferenceshttp://www.123rf.com/photo_5547046_the-bi

g-truck-transport-iron-ore-in-career.htmlhttp://www.cdc.gov/ncbddd/

hemochromatosis/training/pathophysiology/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 .