Bchm Flashcards
Hartnup disease
- defective np AA transporter, which affects their absorption
- triggered by sunlight, fever, drugs, or emotional/physical distress
- aka pellagra like dermatosis
AAs involved in Hartnup disease
Ala, Ser, Thr, Val, Leu, Ile, Phe, Tyr, Trp, Gln, Asn, His
*get excreted 5x normal level
Why does Hartnup often present with skin problems?
Trp is a precursor to serotonin, MELATONIN, and niacin (niacin deficiency is also common)
What almost always precedes a Hartnup attack?
period of poor nutrition
*treatment is directed at niacin repletion (high protein diet and supplements) –>allows production of NAD even though try isn’t there to start the pathway
What causes non classical PKU? PKU?
a. lack of THB
b. Deficiency in phenylalanine hydroxylase
What enzymes are involved in Tyrosinemia type II? type III? type 1?
- Tyrosine aminotransferase (photophobia and skin lesions of palms and soles)
- p-hydroxyphenyl pyruvate oxidase (intermittent ataxia)
- fumarylacetoacetate hydrolyase (hereditary)
What enzyme causes albinism?
tyrosinase
PKU
- deficiency of phenylalanine hydroxylase
- Phe is instead converted to phenylpyruvate and then phenyl lactate* (causes must urine order) and phenyl acetate*
*distrupt neurotransmission and block AA transport in the brain and myelin formation –> severe brain function impairment
How do we treat PKU?
dietary limit Phe (protein supplements without it)
*diagnoses early after birth with Post parturition Guthrie test
Tyrosinemias
- delayed expression of enzymes necessary for Tyr catabolism
- elevated blood levels of tyrosine
What is the problem with Type I tyrosinemias
- cabbage like smell and severe liver failure if not treated because they excrete succinylacetone, which is:
1. toxic to liver and kidneys
2. interferes with TCA cycle
3. causes renal tubule dysfunction
4. inhibits biosynthesis of heme
*most common form; treated with nitisinone
Alkaptonuria
- defective homogentisate oxidase
- leads to accumulation of homogentisic acid–>auto oxidation by light and polymerization of the products produces dark colored pigments in the urine
- black pigmentation in the IV discs, arthritis, and ochonosis (dark CT) are also symtoms
*“Black Urine Disease”
Gout
- Primary hyperuricemia–>overproduction of uric acid
- Secondary hyperuricemia–>under excretion of uric acid
- results in painful deposits of sodium urate in the joints
- diets rich in purines and alcohol induce problems
Hyperammonemia
- defects in any enzyme associated with urea cycle or with 3 specific transporters
- transporters: mitochondrial ornithine carriers, mitochondrial Asp/Glu carrier, and dibasic AA transporter
- treatment: limit protein consumption
What’s unique about defects in ornithine trasncarbamoylase?
it’s x linked
- causes excessive carbamoyl phosphate
- accompanied with hyperammonemia and decreased BUN
