Chapter 23 Flashcards
Angelman Syndrome
defect in member of E3 (ubiquitin ligase) family. severe neurological disorder (mental retardation, absence of speech, uncoordinated movements, hyperactivity)
HPV
uncontrollable protein turnover. Activation of an E3 enzyme. Tumor suppressor is ubiquinated and other proteins that control DNA repair (so they are destroyed)
Liver Damage & Alcoholism
presence of alanine & aspartate aminotransferases in the blood stream because liver cell membranes are damaged so the aminotransferases leak into the blood. Levels are ~ 10 times higher
Hyperammonemia
Elevated level of NH4+. Carbamoyl phosphate synthesis is blocked (or blockage of any steps in urea cycle = defects in the urea cycle)
coma, irreversible brain damage (hepatic encephalopathy) —> this happens because there is no other pathway for the synthesis of urea
Argininosuccinase deficiency
Bypassed by providing a surplus of arginine, benzoate and phenylacetate and following a protein restricted diet. carbamoyl phosphate and aspartate are the sources of N atoms. They are eliminated from the body per molecule of arginine provided in the diet. Argininosuccinate substitutes for urea in carrying nitrogen out of the body.. Nitrogen will emerge as hyppurate, phenylacetyulglutamine & citrulline.
Alcaptonuria
Absence of homogentisate oxidase. Accumulation of this enzyme because degradation is blocked. Excreted in urine, urine is dark. inherited, harmless.
Maple Syrup Urine Disease
oxidative decarboxylation of branched alpha-ketoacids (V, I & L) is blocked because the branched-chain dehydrogenase is missing/defective. The levels of the alpha-ketoacids & branched-chain amino acids are very high. Urine of patients smells like maple syrup. Leads to mental/physical retardation.
Place on diet low in valine, isoleucine & leucine. Can detect the disease by screenings of urine samples with 2,4-dinitrophenolhydrazone derivatives.
Phenylketonuria
absence/deficiency of phenylalanince hydroxylase or tetrahydrobiopterin cofactor. Phenylalanine accumulates in all body fluids because it cannot be converted into tyrosine. Untreated = severely mentally retarded, below average brain weight, defective myelination of nerves & reflexes are hyperactive. Treatment = low phenylalanine diet with tyrosine supplementation. Phenylalanine presence in blood is the diagnosis.
High Homocysteine levels
damage cell lining blood vessels. Increases growth of vascular smooth muscle. Raises oxidative stress. Development of Type 2 diabetes. Treatment with vitamins to maximize the pathway
Porphyriaa (uroporphyrin I)
inherited/acquired disorder. Deficiencey in enzymes of heme biosynthetic pathway. UI = prematurely destroys erythrocytes because of an insufficient cosynthase. Urine is red because of excretion of large amounts of uroporphyrin I.
Severe Combined Immunodeficiency
deficiency in adenosine deaminase activity. This leads to a significant decrease of normal dATP (which inhibits ribonucleotide reductase & DNA synthesis. Symptoms: acute recurring infections (death at an early age). Characterized by a loss of T cells. treated by gene therapy
Gout
high serum levels of urate (hyperuricemia). Painful joint disease where the sodium salt of urate crystallizes in the fluid and the lining of the joints. Painful inflammation results when cells of the immune system engulf the sodium urate crystals (kidney stones too). Treat with allopurinol. Which is an analog of hypoxanthine (first acts as a substrate and then as an inhibitor of Xanthine oxidase –> suicide inhibition)
Why are urate levels kept high?
effective scavenger of ROS, antioxidant (similar to vitamin C) and may protect against ROS
Lesch-Nyhan Syndrome
total absence of hypoxanthine-guanine phosphoribosyltransferase (HGPRT). compulsive self-destructive behaviour Mental deficiency, spasticity, high urate levels = formation of kidney stones. Sex recessive disorder. Lack of HGPRT results in an imbalance of key neurotransmitters
Spina bifida
birth defect characterized by the incomplete or incorrect formation of the neural tube
