Genetic disorders of metabolic pathways Flashcards
what are the essential amino acids
TV FHIL Might Kill Real Women
threonine, valine, phenylalanine, histadine, isoleucine, leucine, methionine, lysine, arginine, tryptophan
signs of phenylketonuria
My MILC
- musty or mousy odor
- microcephaly
- intellectual disability
- light hair, bluish eyes (tyr to melanin metab impaired)
- convulsive movements: gabba neurons impaired
classical PKU is from what
phenylalanine —phenylalanine hydroxylase–> tyrosine
phe hyrdoxylase is defective
-liver specific
what causes secondary PKU and what enzymes involved
PTPS defective prevents synthesis of THB (cofactor req)
-dihydropteridine reductase: recycles DHB to THB
what does phenylalanine get converted to in alternative pathway when phe hydroxylase is defective and what does this cause
phenylpyruvate: interferes with transport of pyruvate into mitchondria in brain
- phenylpyruvate to phenylacetate = musty smell
what can you give as treatment for 2ndary PKU
sepiapterin
consequence of excess phenylalanine
inhibit tyrosinase
excessive phe inhibits what enzymes which causes what
tyrosinase: decrease in pigmentation
5HT decarboxylase: decrease in serotonin
glutamate decarboxylase: decrease GABA syn
how do you treat PKU
diet without phe and supplement with tyrosine
maternal PKU
phe crosses placenta and fetal PAH cannot convert Phe to Tyr
- mental retardation
- microcephaly
alkaptonuria, which enzyme defective
homogentisate oxidase,
-buildup of homogentisate
presentation of alkaptornuria
- typically presents in 20s-30s
- discoloration of sclera
- dark colored urine
- accumulation of HA–> degeneration of cartilage of spine and other major joints
- kidney disease
enyzme defective in albinism
tyrosinase
tyrosinemia type 1:
defective step and converion to what in alternative path
fumarylacetoacetate–fumarylacetoacetate hydrolsae–>acetoacette/fumarate
- fumarylacetoacetate hydrolase defective
- fumarylacetoacetate converted to succinylacetone which is toxic
how is succinylacetone toxic in _____
tyrosinemia
- toxic to liver and kidney
- effects TCA bc of succinly coA
- first rxn in heme syn impaired
homocystinuria defective enzyme
cystathione B-synthase
toxic molecule in alt pathway of homocystinuria
homocysteine thiolactone
-reacts w/ lysine residues
what enzyme can convert homocysteine back to methionine and what cofactors req
methionine synthase
B6,B12,folic acid
clinical features homocystinuria
- stroke
- deep vein thrombosis
- atherosclerosis
- marfan-like haitus
- mental retardation
maple syrum disease, aas involved
valine, isoleucine, leucine
maple syrum disease intermediates that build up
a-ketoisovalerate
- a-keto-B-methylvalerate
- aketoisocaproate
enzyme defective in maple syrup disease
a-ketoacid decarboxylase
presentation of maple syrup urine disease
symptoms 3-4 days after birth
- feeding difficulties, vomitin, lethargic, abnormal muscle tone, coma, death
- elevated BCAAs and a-ketoacids in urine and plasma, burnt sugar smell
- high incidence in mennonite community
what enzymes defective in galactosemia
galactokinase
UDP-glactose-4’-epimerase
-galactose-1-phosphate uridyl transferase
what is the alt pathway in galactosemia
galactatol
-contributes to cataracts and some NS stress
which 2 enzymes are most damaging when defective in galactosemia and why
UDP-glactose-4’-epimerase and galactose-1-phosphate uridyl transferase
- builup of galactose-1-phosphate
- sucks up phosphates in cell and causes phosphate defeciency
- heptaomegaly
galactosemia and infants
infants can’t utilize galactose in milk
- malnutrition, failure to thrive
- galactose accumulates in tissue
- damage to liver brain eyes, mental retardadation
- **cataracts within first few weeks
- vomiting, diarrhea, jaundice, hepatomegaly
