Genetic Disorders of Metabolic Pathways Flashcards
What are the Essential Amino Acids?
Amino Acids that we need to obtain in our diet (our body does not make them!)
PVT TIM HALL
Proline, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Arginine, Leucine, Lysine
What are the only 2 sulfur containing Amino Acids?
- Methionine
2. Cysteine (Can make cysteine from Methionine)
What are some general clinical presentations of Phenylketonuria (PKU)?
- Light Hair, BLUISH eyes
- CNS issues
- Body Odor –> “musty” or “mousy”
- Only 25% live beyond 30 years
- HIGH levels of Phenylalanine in the blood! (100 x)
Describe the deficiency related to PRIMARY PKU.
- Deficient Phenylalanine Hydroxylase
- Build-up of Phenylalanine
- LOW Tyrosine
Describe the deficiency related to SECONDARY PKU.
- Involves the Insufficiency of Tetrahydrobiopterin (BH4)
- Deficiency in DIHYDROPTERINE Reductase
- If you don’t have BH4, then you are NOT going to be able to convert Phenyalanine into TYROSINE
What are some side compounds that are generated in response to the buildup of Phenylalanine? What happens when there are high levels of these compounds in the blood?
- Phenylacetate (gives the “musty odor”)
- Phenylpyruvate
- Phenyllactate
HIGH levels of these compounds in blood will BLOCK amino acid transport into the brain as well as MYELIN formation
What is an enzyme that is inhibited with HIGH Phenylalaine levels in newborns? Why is diagnosis so crucial?
- Tyrosinase: Decrease in pigmentation (melanin)
- Loss of 5-IQ units every 10 weeks of delayed treatment
Describe the Guthrie Test.
- Bacteria are frozen that need Phenylalanine to grow
- If you have HIGH levels of Phenylalanine in the blood, when you put the blood on the agar plate, it will STIMULATE the bacteria to grow
What can Mass tandem spectrophotometry do?
Can give a detailed report on exactly which AMINO ACIDS are elevated in Blood and/or urine
Can Phenylalanine from the mother cross the placenta?
YES (Maternal PKU)
What is the main enzyme that is deficient in Alkaptouria?
Homogentisate Oxidase
Describe some characteristics associated with Alkaptouria.
- Autosomal Recessive
- Presents in 20’s-30’s
- Dark-colored urine
- Accumulation of HOMOGENTISATE (analogous to melanin)
- Darkenend SCLERA
- Degeneration of cartilage in JOINTS
Describe some characteristics associated with Albinism.
- Autosomal Recessive
- Unable to synthesize Melanin
- Ocular defects
- Increased RISK of basal cell and squamous carcinomas!
Which enzyme is deficient in Albinism?
Tyrosinase (Build-up of Tyrosine)
- Cannot synthesize MELANIN!
Which enzyme is deficient in Type I Tyrosinemia?
Fumarylacetoacetate hydrolase (Build-up of Fumarylacetoacetate)
List some characteristics associated with Type I Tyrosinemia.
- MOST COMMON and MOST SERIOUS
- Infants have Cabbage-Like Odor
- Liver and Kidney failure
What is the side product that builds-up in Type I Tyrosinemia?
Succinylacetone
Which enzyme is deficient in Type II Tyrosinemia?
Tyrosine aminotransferase (Build-up of TYROSINE)
List some characteristics associated with Type II Tyrosinemia.
- Tyrosine build-up
- Tyrosine goes to the EYES and the SKIN (Oculocutaneous Tyrosinemia)
- Crystals will form!
Which enzyme is deficient in Type III Tyrosinemia?
p-Hydroxyphenylpyruvate Oxidase (Build-up of p-Hydroxyphenylpyruvate)
List some characteristics associated with Type III Tyrosinemia.
- Severe mental retardation occurs
What is the Therapuetic intervention for patients with Type I Tyrosenima?
NITISINONE: Reversible inhibitor of p-hydroxyphenylpyruvate oxidase; prevents the formation of fumarylacetoacetate which is the PRECURSOR to succinylacetone
What is an important product that needs to be made before the synthesis of Melanins?
Dopa-quinone
Which enzyme is deficient in Classic Homocystinuria?
Cystathionine B-Synthase
What disorders might hapen when you have a build-up of homocystine?
- Stroke
- Athlersclerosis
- DVT
- Mental Retardation (Cysteine and Sulfur Impairment)
- Joint Contractures (GAGs)
- MARFAN-LIKE habitus: Tall Stature/Long Figures
Cysteine is crucial to which structures?
- Glutathione (Maintains cytoprotection)
- Acetameinophen overdose will cause Liver failure due to Glutathione DEPLETION - GAGs (i.e. heparin sulfate): Important component of Connective Tissue and Bone
What is a Co-Factor for Cystathionine B-Synthase?
Pyridoxine (B6)
Which enzyme is deficient in Maple Syrup Urine Disease?
a-Ketoacid dehydrogenase
Maple Syrup Urine Disease involves which amino acids?
- Valine
- Isoleucine
- Leucine (Leucine is going to saturate the receptors for brain so you will not get Phenylalanine and Tyrosine in)
(Branched-Chain Amino Acids)
What are some characteristics associated with Maple Syrup Urine Disease?
- Autosomal Recessive
- Symptoms appear 3-4 days after birth (feeding difficulties, lethargic, progressive neurodegeneration, abdnormal muscle tone, coma, death)
- ELEVATED BCAAs and a-ketoacids (Burnt sugar smell)
Which enzyme is deficient in Galactosemias?
Galactose-1-phosphate Uridyl Transferase (Build-up of Galactose-1-Phosphate)
What are some characteristics associated with Galactosemias?
- Trapping Galactose in the TISSUE by not being able to remove the Phosphate
- CATARACTS appear due to the build-up of GALACTITOL (Produces CNS issues)
- Galactose especially accumulates in the LIVER
Keto acid dehydrogenase enzyme complex is similar to which other family of enzyme complexes?
- Pyruvate Dehydrogenase
2. a-ketoglutarate Dehydrogenase
