Lecture 48: Amino acidopathies: defects in amino acid metabolism

Question 1

What amino acidopathies?

Answer 1

They are inborn errors of metabolism commonly caused by mutant genes that generally result in abnormal proteins, usually enzymes

Question 2

A deficiency in which enzyme causes phenylketonuria?

Answer 2

phenylalanine hydroxylase

Question 3

What is the general treatment for amino acidopathies?

Answer 3

Diets low in amino acids whose catabolism is impaired

Question 4

Aside from phenylalanine, which is 10X elevated in phenylketonuria, what else is elevated?

Answer 4

phenylpyruvate, phenyllactate, phenylacetate

Question 5

What are the major symptoms of phenylketonuria?

Answer 5

Hypopigmentation
CNS symptoms (intellectual disability, developmental delay, microcephaly, seizures in untreated PKU patients)

Question 6

What is the treatment of phenylketonuria?

Answer 6

dietary restriction of Phe

Question 7

What are two other causes of hyperphenylalanemia?

Answer 7

deficiencies in any of the enzymes required to synthesize BH4

deficiency in dihydropteridine reductase which regenerates BH4 from BH2

Question 8

How common is maple syrup urine disease?

Answer 8

1:185000 (autosomal recessive)

Question 9

What causes MSUD?

Answer 9

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

Question 10

What are some symptoms and treatments for MSUD?

Answer 10

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.

Question 11

What causes albinism?

Answer 11

Absent or defective copper requiring tyrosinase deficiency

Question 12

What are some symptoms?

Answer 12

White hair, pink eyes, hypopogemented pale skin, sensitivity to sunlight, impaired vision, and photophobia

Question 13

What is the treatment for albinism?

Answer 13

protection from UV exposure

Question 14

What are the two types of melanin?

Answer 14

Eumelanin

Pheomelanin

Question 15

What is melanin used for in humans?

Answer 15

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.

Question 16

5,6 DHI and 5,6 DHICA are the two polymers that are cross-linked to form pheomelanin polymers.

Answer 16

False. They form eumelanin polymers.

Question 17

What are the two recognized types of eumelanin?

Answer 17

black (small amount in absence of others causes grey hair)

brown (small amount in absence of others causes blond hair)

Question 18

Where is pheomelanin particularly concentrated?

Answer 18

It gives a red/pink hue and is concentrated in the lip, nipples, glans of the penis and vagina.

Question 19

How does pheomelanin differ from eumelanin?

Answer 19

Its oligomer structure incorporates benzothiazine and benzothiazole instead of DHI and DHICA

Question 20

What is homocystinuria?

Answer 20

It is a rare group of disorders involving defects in metabolism of homocysteine.

Question 21

What are some symptoms of homocystininuria?

Answer 21

lens dislocation, skeletal abnormalities, intellectual disabilities, increased risk for blood blots

Question 22

What are the treatments for homocystininuria?

Answer 22

Treatment includes restriction of methionine and supplementation with B6 and B12, and folate

Question 23

What is alkaptonuria?

Answer 23

It is a rare, non-fatal condition involving a deficiency in homogentisic acid oxidase causing the accumulation of homogentisic acid (HA)

Question 24

What are the three characteristic symptoms of alkaptonuria?

Answer 24

1. homogentisic aciduria (HA in urine oxidizes to a dark pigment)
2. large joint arthritis
3. deposition of black pigment in cartilage and collagenous tissue

Question 25

Where is NO synthesized from?

Answer 25

It is synthesized from arginine by nitric oxide synthase

Question 26

What are the three NOS encoded by different genes?

Answer 26

1. endothelial
2. neural
3. inducible

Question 27

What is so special about NOS?

Answer 27

It has many cofactors: NADPH, FMN,FAD, heme, O2, tetrahydrobiopterin

Question 28

T/F: NO is the most important mediator of penis dilation in response to parasympathetic nerve stimulation.

Answer 28

True.

Question 29

What sildenafil do?

Answer 29

It inhibits phosphodiesterase-5 which is responsible for the degradation of cGMP which helps with vasodilation of the penis.