Lecture 48: Amino acidopathies: defects in amino acid metabolism Flashcards
What amino acidopathies?
They are inborn errors of metabolism commonly caused by mutant genes that generally result in abnormal proteins, usually enzymes
A deficiency in which enzyme causes phenylketonuria?
phenylalanine hydroxylase
What is the general treatment for amino acidopathies?
Diets low in amino acids whose catabolism is impaired
Aside from phenylalanine, which is 10X elevated in phenylketonuria, what else is elevated?
phenylpyruvate, phenyllactate, phenylacetate
What are the major symptoms of phenylketonuria?
Hypopigmentation CNS symptoms (intellectual disability, developmental delay, microcephaly, seizures in untreated PKU patients)
What is the treatment of phenylketonuria?
dietary restriction of Phe
What are two other causes of hyperphenylalanemia?
deficiencies in any of the enzymes required to synthesize BH4
deficiency in dihydropteridine reductase which regenerates BH4 from BH2
How common is maple syrup urine disease?
1:185000 (autosomal recessive)
What causes MSUD?
partial or complete deficiency in mitochondrial branched chain alpha keto acid dehydrogenase that oxidatively carboxylates Leu, Ile, and Val
BCAAs and their corresponding alpha keto acids accumulate in the blood causing interferance with brain function
What are some symptoms and treatments for MSUD?
Symptoms: maple syrup odor to urine due to rise in Ile, feeding problems, ketoacidosis, changes in muscle tone, neurologic problems
Treatment: synthetic formula free of BCAAs and supplemented with a limited amounts of Leu, Ile, and Val to allow normal growth and development without producing toxic levels.
What causes albinism?
Absent or defective copper requiring tyrosinase deficiency
What are some symptoms?
White hair, pink eyes, hypopogemented pale skin, sensitivity to sunlight, impaired vision, and photophobia
What is the treatment for albinism?
protection from UV exposure
What are the two types of melanin?
Eumelanin
Pheomelanin
What is melanin used for in humans?
It is the determinant of skin color and is found in the hair, iris and stria vascularis. Melanin can also be found in the brain.
5,6 DHI and 5,6 DHICA are the two polymers that are cross-linked to form pheomelanin polymers.
False. They form eumelanin polymers.
What are the two recognized types of eumelanin?
black (small amount in absence of others causes grey hair)
brown (small amount in absence of others causes blond hair)
Where is pheomelanin particularly concentrated?
It gives a red/pink hue and is concentrated in the lip, nipples, glans of the penis and vagina.
How does pheomelanin differ from eumelanin?
Its oligomer structure incorporates benzothiazine and benzothiazole instead of DHI and DHICA
What is homocystinuria?
It is a rare group of disorders involving defects in metabolism of homocysteine.
What are some symptoms of homocystininuria?
lens dislocation, skeletal abnormalities, intellectual disabilities, increased risk for blood blots
What are the treatments for homocystininuria?
Treatment includes restriction of methionine and supplementation with B6 and B12, and folate
What is alkaptonuria?
It is a rare, non-fatal condition involving a deficiency in homogentisic acid oxidase causing the accumulation of homogentisic acid (HA)
What are the three characteristic symptoms of alkaptonuria?
- homogentisic aciduria (HA in urine oxidizes to a dark pigment)
- large joint arthritis
- deposition of black pigment in cartilage and collagenous tissue
Where is NO synthesized from?
It is synthesized from arginine by nitric oxide synthase
What are the three NOS encoded by different genes?
- endothelial
- neural
- inducible
What is so special about NOS?
It has many cofactors: NADPH, FMN,FAD, heme, O2, tetrahydrobiopterin
T/F: NO is the most important mediator of penis dilation in response to parasympathetic nerve stimulation.
True.
What sildenafil do?
It inhibits phosphodiesterase-5 which is responsible for the degradation of cGMP which helps with vasodilation of the penis.
