Porphyrins
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Transcript of Porphyrins
PorphyrinsPorphyrins
The Distribution Pattern of Porphyrins in Urine Serves as a
Functional “Fingerprint” of Toxicity
What Are Porphyrins?
•Porphyrins, measured in urine, serve as biomarkers of the effects of toxins on thebiomarkers of the effects of toxins on the heme biosynthetic pathway.
•Heme is essential for proper functioning of many p p g yproteins including oxygen transport, energy production, and detoxification
What Are Porphyrins?
•Heme is a large iron‐binding protein and is synthesized in most tissues, mainly liver and bone marrow
•The pathway to heme manufacture is a series of intermediate compounds calledintermediate compounds called porphyrinogens
What AreWhat Are Porphyrins?
Metal Inserted into Protoporphyrin Resulting Compoundp p yRing
g p
Magnesium Chlorophyll (green plants)
Copper Hemocyanin (crustaceans)
Cobalt Cobalamin (B12)
Iron HemeIron Heme
Why Evaluate Porphyrins?
1. The pathway is highly active, so any disturbance tends to cause rapid and relatively large accumulations of intermediates.
2 Th f h h i d i h2. The enzymes of the porphyrin‐producing pathway are widely distributed in human tissues and some of them are highly sensitive to the presence ofof them are highly sensitive to the presence of various toxins.
3 Pathway makes heme and cytochomes (P‐4503. Pathway makes heme and cytochomes (P 450 enzymes and mitochondrial function). Therefore damage causes major effects on energetics and detoxification
Porphyrins Testing Can…Porphyrins Testing Can…
• Identify Level of Biochemical Damage Caused by Toxicant
Exposure
• Identify Level of Mercury’s Effect
• Monitor Patients Before and During Chelation Therapy
• Identify Toxicity of Therapeutic Drugs
• Differentiate Type of Heavy Metal Toxicityyp y y
Toxicity Often C ibContributes to…
• Multiple Chemical Sensitivity
• Behavioral and Learning Disorders• Behavioral and Learning Disorders
• Immune Dysfunctions
• Chronic Fatigue
• Neurological and Mental/Emotional Disorders
EffectsEffects of Toxic
Exposures: EnzymeEnzyme
Interference
Effects of Inherited PorphyriasEffects of Inherited Porphyrias
Environmental T i I d dToxin‐Induced Porphyrinurias
Levels of Three Porphyrins Following Consecutive DMPS Injections
PingreePingree SD, et al. SD, et al. ToxicolToxicol Sci. 2001;61(2):234Sci. 2001;61(2):234‐‐240.240.
Hypothetical Relationship of Body Levels of Mercury and Porphyrins
P O id R i i f M lPro‐Oxidant Reactivity of Metals and Other Toxic Chemicals Can:and Other Toxic Chemicals Can:
• Inactivate porphyrinogenic enzymes p p y g y• Deplete glutathione and other antioxidants • Increase oxidant stressIncrease oxidant stress
• In addition, porphyrinogens (precursors toIn addition, porphyrinogens (precursors to porphyrins in the reduced state) are easily nonenzymatically oxidized to porphyrins by y y p p y ytoxic metals.
Case Study 1yA patient’s Porphyrins test was unremarkable, except for a slightly elevated Copro I/Copro IIexcept for a slightly elevated Copro I/Copro II ratio, which can be indicative of Arsenic exposureexposure
Case Study Case Study 11
The patient followed up with a whole blood toxic element analysis and was found to havetoxic element analysis and was found to have slightly elevated Arsenic
Case Study Case Study 11
Case Study 2Case Study 2
Clear Porphyrin Profile in Health CheckClear Porphyrin Profile in Health Check.
Case Study Case Study 22
Low Porphyrins Corroborated with Low Toxic MineralsLow Toxic Minerals
Case Study Case Study 22
Case Study 3Case Study 3
Known Mercury Exposure in Autistic ChildKnown Mercury Exposure in Autistic Child
Case Study Case Study 33
Child’s Challenged Urine
Case Study Case Study 33