The Distribution Pattern of Porphyrins in Urine Serves as a Functional “Fingerprint” of Toxicity

1. Porphyrins
The Distribution Pattern of
Porphyrins in Urine Serves as a
Functional “Fingerprint” of Toxicity

2. What Are Porphyrins?
•Porphyrins, measured in urine, serve as
biomarkers of the effects of toxins on the
biomarkers of the effects of toxins on the
heme biosynthetic pathway.
•Heme is essential for proper functioning of many
pp g y
proteins including oxygen transport, energy
production, and detoxification

3. 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 called
intermediate compounds called
porphyrinogens

4. What Are
What Are
Porphyrins?
Metal Inserted into Protoporphyrin
p py Resulting Compound
g p
Ring
Magnesium Chlorophyll (green plants)
Copper Hemocyanin (crustaceans)
Cobalt Cobalamin (B12)
Iron Heme

5. Why Evaluate Porphyrins?
1. The pathway is highly active, so any disturbance
tends to cause rapid and relatively large
accumulations of intermediates.
2. The enzymes of the porphyrin‐producing pathway
2 Th fh hi di h
are widely distributed in human tissues and some
of them are highly sensitive to the presence of
of them are highly sensitive to the presence of
various toxins.
3. Pathway makes heme and cytochomes (P 450
3 Pathway makes heme and cytochomes (P‐450
enzymes and mitochondrial function). Therefore
damage causes major effects on energetics and
detoxification

6. Porphyrins Testing Can…
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 Toxicity
yp y y

7. Toxicity Often
Contributes to…
C ib
• Multiple Chemical Sensitivity
• Behavioral and Learning Disorders
Behavioral and Learning Disorders
• Immune Dysfunctions
• Chronic Fatigue
• Neurological and Mental/Emotional Disorders

8. Effects
Effects
of Toxic
Exposures:
Enzyme
Enzyme
Interference

9. Effects of Inherited Porphyrias
Effects of Inherited Porphyrias

10. Environmental
Toxin‐Induced
T i Id d
Porphyrinurias

11. Levels of Three Porphyrins Following
Consecutive DMPS Injections
Pingree SD, et al. Toxicol Sci. 2001;61(2):234‐240.
SD, et al. Toxicol Sci. 2001;61(2):234‐

12. Hypothetical Relationship of
Body Levels of Mercury and Porphyrins

13. Pro‐Oxidant Reactivity of Metals
P O id R ii fM l
and Other Toxic Chemicals Can:
and Other Toxic Chemicals Can:
• Inactivate porphyrinogenic enzymes
p py g y
• Deplete glutathione and other antioxidants
• Increase oxidant stress
Increase oxidant stress
• In addition, porphyrinogens (precursors to
In addition, porphyrinogens (precursors to
porphyrins in the reduced state) are easily
nonenzymatically oxidized to porphyrins by
y y p py y
toxic metals.

14. Case Study 1
y
A patient’s Porphyrins test was unremarkable,
except for a slightly elevated Copro
except for a slightly elevated Copro I/Copro II
II
ratio, which can be indicative of Arsenic
exposure
Case Study 1
Case Study 1

15. The patient followed up with a whole blood
toxic element analysis and was found to have
toxic element analysis and was found to have
slightly elevated Arsenic
Case Study 1
Case Study 1

16. Case Study 2
Case Study 2
Clear Porphyrin Profile in Health Check.
Clear Porphyrin Profile in Health Check
Case Study 2
Case Study 2

17. Low Porphyrins Corroborated with
Low Toxic Minerals
Low Toxic Minerals
Case Study 2
Case Study 2

18. Case Study 3
Case Study 3
Known Mercury Exposure in Autistic Child
Known Mercury Exposure in Autistic Child
Case Study 3
Case Study 3

19. Child’s Challenged Urine
Case Study 3
Case Study 3