Disorders of AA Catabolism

Question 1

what is deficient in phenylketonuria (PKU)?

Answer 1

the enzyme phenylalanine hydroxylase (classical PKU, PKU- I)

Question 2

deficiency in phenylalanine hydroxylase leads to?

Answer 2

elevated Phe in serum and reduced Tyr

Question 3

what are alternative products if defect in phenylalanine hydroxylase

Answer 3

phenylpyruvate, phenylacetate, phenyllactate (excreted in urine - mousey odor of urine)

Question 4

What happens as a result of decreased Tyr in phenylketonuria

Answer 4

becomes an essential AA and decreased pigmentation of skin and hair (not much substrate for tyrosinase to use to turn into melanin)

Question 5

Symptoms of PKU

Answer 5

low IQ (CNS), seizures (high phe in blood)

Question 6

why do you test infant twice for phenylalanine levels?

Answer 6

first test might give a false negative because of maternal PHE clearance

Question 7

Treatment for PKU

Answer 7

low Phe diet (low protein) immediately after diagnosis, monitor blood Phe levels, avoid artificial sweetener Aspartame, Tyr supplement in diet, Sapropterin (synthetic BH4)

Question 8

Enzyme from Phe to Tyr

Answer 8

Phenylalanine hydroxylase using BH4

Question 9

What happens with child of preggo women with PKU if they do not maintain low Phe level?

Answer 9

kids have defects: microcephaly, mental retardation, congenital heart defects

Question 10

what is deficient in PKU Types II and III

Answer 10

dihydrobiopterin reductase/dihydrobiopterin synthesis which leads to lack of BH4

Question 11

Why are CNS symptoms for PKU II and III worse?

Answer 11

decreased synthesis of neurotransmitters such as serotonin, dopamine, catecholamines –> all need BH4

Question 12

Treatment for PKU II and III

Answer 12

low Phe diet and supplement for biopterin and precursors for neurotransmitters

Question 13

what are the 3 enzymes used to get from Tyr to fumarate and acetoacetate

Answer 13

From Tyr to hemogentisate, use Tyr aminotransferase (PLP needed)

From hemogentisate to fumarate and acetoacetate, use hemogentisate oxidase and fumaryl acetoacetate hydrolase

Question 14

deficient in alkaptonuria?

Answer 14

hemogentisate oxidase which can cause arthritis

Question 15

manifestations of alkaptonuria

Answer 15

blueish black discoloration of sclera and auriculum, dark urine, build up of hemogentisate

Question 16

Treatment for alkaptonuria

Answer 16

dietary restriction of Phe and Tyr

Question 17

deficient in tyrosinosis (tyroseinemia type I and II)

Answer 17

Type I: fumaryl acetoacetate hydrolase

Type II: Tyr aminotransferase

Question 18

Manifestations of Tyrosinosis

Answer 18

Type I: build up of fumaryl acetoacetate, liver and kidney damage, death

Type II: lesions in the eye and skin, neurological probs

Question 19

deficient in maple syrup urine disease (MSUD)

Answer 19

branch chain alpha ketoacid dehydrogenase using TPP (branched chain AA include val, ile, leu - enzyme used in the first step)

Question 20

manifestations of MSUD

Answer 20

ketosis, maple syrup odor of urine, poor feeding, vomiting, poor weight gain, increasing lethargy, neurological signs (seizures etc), coma, death

Question 21

treatment of MSUD

Answer 21

dietary restriction of branched chain AA 4 life! monitor blood BCAA levels, supplement TPP (thiamine) for those with a variation of the disease where there’s a low coenzyme affinity

Question 22

problems that may arise when treating MSUD

Answer 22

BCAA are abundant in most proteins (so what then could they eat?), 3 BCAA are essential AA, catabolic state mobilize tissue protein which then release AA to metabolism (whatever tf this means)

Question 23

Deficient in methylmalonic aciduria

Answer 23

the enzyme methylmalonyl CoA mutase

Question 24

manifestations of deficient methylmalonyl CoA mutase

Answer 24

build up of methylmalonyl CoA (converts to methylmalonic acid when accumulated), metabolic acidosis, methylmalonic aciduria/acidaemia, FA formed with methylmaloyl coA instead of malonyl CoA so BCAA in membrance –> seizure and encephalopathy

Question 25

Treatment for methylmalonic aciduria

Answer 25

B12 supplementation, diets low in BCAA

Question 26

how do you go from Met to Cys

Answer 26

Met (using SAM and SAH) --> Homocysteine (using Ser and PLP or Cystathionine Beta Synthase and PLP ) --> Cystathionine (using Cystathionase and PLP with Vit B6) --> Cysteine Homocysteine can also go back to Met using Vit B12 and THF(B9)

Question 27

Fate of cysteine formed in Met-Cys Pathway

Answer 27

catabolized to sulfate which can be excreted in urine or using ATP can go into making PAPs

Question 28

deficiency in homocystinuria

Answer 28

cystathione beta synthase (hence build up of homocysteine in serum and urine) or deficiency in the coenzymes Vitamin B12, B6, and B9 (folic acid)

Question 29

manifestations of homocystinuria

Answer 29

[[[[dislocation of lens]]]], skeletal abnormalities, osteoporesis, premature arterial disease, mental retardation

Question 30

treatment of homocystinuria

Answer 30

Vitamin B6 supplement (precursor for PLP), dietary restriction of Met, supplementation with folic acid (B9), and vitamin B12

Question 31

link between homocysteine and atherosclerosis

Answer 31

homocysteine binds to connective tissue and disrupts its structure, ability to generate superoxide and H2O2, formation of reactive homocysteine and homocysteine thiolactone