In this high-yield review, you will learn about the biochemical role of tetrahydrobiopterin and the related clinical condition Segawa Syndrome. People with some forms of phenylketonuria take tetrahydrobiopterin supplement (BH4 supplement). We will learn the biochemical basis of that also. Do not forget to watch the YouTube video.

1. Tetrahydrobiopterin
Including Segawa Syndrome
Dr. Karthikeyan Pethusamy

2. Pteridine Pterin Biopterin
Dr. Karthikeyan Pethusamy

3. THB
• Tetrahydrobiopterin (THB) is a pteridine ring containing
heterocyclic compound.
• Vitamins folic acid and riboflavin also contain pteridine
ring.
• In humans, THB is NOT a vitamin as it can be synthesised in
our body.
Dr. Karthikeyan Pethusamy

4. Synthesis
• Guanosine Triphosphate is the
precursor.
• 3 enzymes are involved.
• The first one, GTP cyclohydrolase
I is the rate limiting.
Dr. Karthikeyan Pethusamy

5. Guanine
Pterin
Dr. Karthikeyan Pethusamy

6. Cofactor
Role
• Phenyl alanine  Tyrosine
• Tyrosine  DOPA
• Tryptophan  5-OH tryptophan
Aromatic amino
acid
hydroxylases
Arginine  Citruline + NO
Nitric oxide
synthase (NOS)
• Ether lipid  Glycerol + Aldehyde
Glyceryl ether
monooxygenase
Dr. Karthikeyan Pethusamy

7. Phenylalanine
Hydroxylase
Dr. Karthikeyan Pethusamy

8. Cofactors
for Nitric
Oxide
Synthase
NADPH
FAD
FMN
Heme
TetrahydrobiopterinDr. Karthikeyan Pethusamy

9. Dopa-
Responsive
Dystonia
or
Segawa variant
(DYT5)
Autosomal dominantly inherited form of
childhood-onset dystonia
Decreased activity of GTP cyclohydrolase-
I due to mutation
Tyrosine to DOPA conversion is impaired
Rx: Levodopa
Ref. Harrison, 20th edition p.2620
Dr. Karthikeyan Pethusamy