Disorders of AA Catabolism Flashcards
what is deficient in phenylketonuria (PKU)?
the enzyme phenylalanine hydroxylase (classical PKU, PKU- I)
deficiency in phenylalanine hydroxylase leads to?
elevated Phe in serum and reduced Tyr
what are alternative products if defect in phenylalanine hydroxylase
phenylpyruvate, phenylacetate, phenyllactate (excreted in urine - mousey odor of urine)
What happens as a result of decreased Tyr in phenylketonuria
becomes an essential AA and decreased pigmentation of skin and hair (not much substrate for tyrosinase to use to turn into melanin)
Symptoms of PKU
low IQ (CNS), seizures (high phe in blood)
why do you test infant twice for phenylalanine levels?
first test might give a false negative because of maternal PHE clearance
Treatment for PKU
low Phe diet (low protein) immediately after diagnosis, monitor blood Phe levels, avoid artificial sweetener Aspartame, Tyr supplement in diet, Sapropterin (synthetic BH4)
Enzyme from Phe to Tyr
Phenylalanine hydroxylase using BH4
What happens with child of preggo women with PKU if they do not maintain low Phe level?
kids have defects: microcephaly, mental retardation, congenital heart defects
what is deficient in PKU Types II and III
dihydrobiopterin reductase/dihydrobiopterin synthesis which leads to lack of BH4
Why are CNS symptoms for PKU II and III worse?
decreased synthesis of neurotransmitters such as serotonin, dopamine, catecholamines –> all need BH4
Treatment for PKU II and III
low Phe diet and supplement for biopterin and precursors for neurotransmitters
what are the 3 enzymes used to get from Tyr to fumarate and acetoacetate
From Tyr to hemogentisate, use Tyr aminotransferase (PLP needed)
From hemogentisate to fumarate and acetoacetate, use hemogentisate oxidase and fumaryl acetoacetate hydrolase
deficient in alkaptonuria?
hemogentisate oxidase which can cause arthritis
manifestations of alkaptonuria
blueish black discoloration of sclera and auriculum, dark urine, build up of hemogentisate
Treatment for alkaptonuria
dietary restriction of Phe and Tyr
deficient in tyrosinosis (tyroseinemia type I and II)
Type I: fumaryl acetoacetate hydrolase
Type II: Tyr aminotransferase
Manifestations of Tyrosinosis
Type I: build up of fumaryl acetoacetate, liver and kidney damage, death
Type II: lesions in the eye and skin, neurological probs
deficient in maple syrup urine disease (MSUD)
branch chain alpha ketoacid dehydrogenase using TPP (branched chain AA include val, ile, leu - enzyme used in the first step)
manifestations of MSUD
ketosis, maple syrup odor of urine, poor feeding, vomiting, poor weight gain, increasing lethargy, neurological signs (seizures etc), coma, death
treatment of MSUD
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
problems that may arise when treating MSUD
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)
Deficient in methylmalonic aciduria
the enzyme methylmalonyl CoA mutase
manifestations of deficient methylmalonyl CoA mutase
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
Treatment for methylmalonic aciduria
B12 supplementation, diets low in BCAA
how do you go from Met to Cys
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)
Fate of cysteine formed in Met-Cys Pathway
catabolized to sulfate which can be excreted in urine or using ATP can go into making PAPs
deficiency in homocystinuria
cystathione beta synthase (hence build up of homocysteine in serum and urine) or deficiency in the coenzymes Vitamin B12, B6, and B9 (folic acid)
manifestations of homocystinuria
[[[[dislocation of lens]]]], skeletal abnormalities, osteoporesis, premature arterial disease, mental retardation
treatment of homocystinuria
Vitamin B6 supplement (precursor for PLP), dietary restriction of Met, supplementation with folic acid (B9), and vitamin B12
link between homocysteine and atherosclerosis
homocysteine binds to connective tissue and disrupts its structure, ability to generate superoxide and H2O2, formation of reactive homocysteine and homocysteine thiolactone
