Metabolism Disorders

Question 1

Why does phenylketonuria occur?

Answer 1

Due to decreased phenylalanine hydroxylase or decreased tetrahydrobioterin (BH4)

Question 2

What amino acid becomes essential in phenylketonuria?

Answer 2

Tyrosine becomes essential because phenylalanine can not be converted into tyrosine in the body due to decreased phenylalanine hydroxylase

Question 3

What are the clinical findings in phenylketonuria?

Answer 3

• Intellectual disability
• Growth retardation
• Seizures
• Fair skin
• Eczema
• Musty body odor

Question 4

How is phenylketonuria treated?

Answer 4

• Decreased dietary phenylalanine
• Increased dietary tyrosine
• Tetrahjydrobiopterin supplementation

Question 5

How is phenylketonuria acquired?
When do you screen for it?
What are the phenyl ketones found?
What kind of disorder is it and what does it lead to?
What do patients have to avoid?

Answer 5

• Autosomal recessive (1:10,000)
• Screen 2-3 days after birth
• Phenyl acetate, phenyl lactate and phenylpyruvate
• Disorder of aromatic amino acid metabolism leads to musty body odor
• Artificial sweeteners such as aspartame which contains phenylalanine

Question 6

What is tetrahydrobiopterin (BH4) a cofactor for?

Answer 6

Its a cofactor for the synthesis of serotonin, tyrosine and DOPA

1. Phenylalanine >BH4> Tyrosine >BH4> DOPA
   - Dopa can then be converted to catecholamines or melanin
2. Tryptophan >BH4> 5-hydroxytryptophan > 5-hydroxytryptamine (Serotonin)

Question 7

What is the most common fatty oxidation disorder?

Answer 7

Medium-chain acyl-CoA dehydrogenase deficiency

Question 8

What is medium-chain acyl-coA dehydrogenase deficiency?

Answer 8

• Inability to break down fatty acids into acetyl-CoA

- Leads to accumulation of fatty acyl carnitines in the blood with hypoketotic hypoglycemia

Question 9

What are the symptoms seen in medium-chain acyl-coA dehydrogenase deficiency?

Answer 9

• Vomiting
• Lethargy
• Seizures
• Coma
• Liver dysfunction
• Can lead to sudden death in infants or children
• Treat by avoiding fasting

Question 10

In the presence of O2, pyruvate produced from glycolysis is converted into what? By which enzyme?

Answer 10

• Converted into Acetyl CoA
• By pyruvate dehydrogenase
• It is then metabolized by oxidative phosphorylation

Question 11

In the absence of O2, pyruvate produced from glycolysis is converted into what? By which enzyme?

Answer 11

• Converted into lactae or lactic acid
• By lactate dehydrogenase
• Leads to lactic acidosis