Tom's wagners high yield- biochem Flashcards
Orotic Aciduria
Deficiency in UMP Synthase–> increased orotic acid in urine and megaloblastic anemia No hyperammonemia (hyperammonemia–>Ornithine Transcarbamolase Deficiency)
Lesch-Nyhan Syndrome defect
HGPRT deficiency, X-linked recessive
3’->5’ exonuclease activity
DNA Pol III and I;
Defective Endonuclease repair of pyrimidine dimers
Increased risk for SqCC, Basal CC, Melanoma
Glycosylase (removes altered base)
Endonuclease (5’) then Lyase (3’)
DNA Pol then DNA Ligase
repairs spontaneous/toxic deamination of bases
I: rRNA, II: mRNA, III:tRNA. toxin?
Amantinin (mushroom toxin) inhibits RNA Pol II (mRNA synthesis–>hepatotoxic)
5’ Cap, 3’ Polyadenylation, Splicing
inital transcript is hnRNA (heterogenous nuclear RNA)
P-Bodies
contain exonucleases, decapping enzymes, and microRNAs
CCA at 3’ end
Added as a post-translational modification, ATP used to charge the tRNA
75-90 nucleotides, including Dihydrouricil and Pseudouridine. Dihydrouricil use?
Dihydrouracil in D arm necessary for binding the correct aminoacyl-tRNA synthase
RER-secreted; free ribosomes-cytosolic/organellar found in what cells?
Mucus-secreting Goblet cells, Plasma cells, and Chief cells (stomach-pepsinogen) are rich in RER
Mannose-6-Phosphate defect?
Deficient in I cell disease–lysosomal proteins excreted, coarse facial features, clouded corneas, high plasma lysosomal enzymes, restricted joint movement, can be fatal
Kartagener’s Disease defect?
dynein arm defect in cilia
1/3 of collagen is?
Glycine (1/3 of collagen is glycine) . Gly-X-Y
RER: what part of collagen sysnthesis?
decreases hydroxylation of proline and lysine. Problems w/ formation of triple helix in RER (3 alpha chains)
Menkes Disease needs what?
Copper is necessary cofactor for Lysyl oxidase–> Crosslinks collagen (extracellular)
AutoDom, decreased production of otherwise normal collagen. S/s? Name dz
Multiple fx w/ minimal trauma, blue Sclera (due to translucency of collagen over choroidal veins); Hearing loss (abnormal ossicles), and dental imperfections
osterogeneisis imperfecta
Faulty Collagen synthesis (6 types)
Can involve joint hypermobility, skin hyperextensability (Type 5 collagen)
Berry and Aortic Aneurysms (Type 3 collagen–blood vessels)
Southern: DNA; Northern: RNA; West: Protein. SW blot?
Southwestern: DNA-binding proteins. need a doubel stranded DNA probe
Presence of both normal and mutated mtDNA
Results in variable expression of mitochondrially-inherited disease between family members; Disease extent corrolates to the proportion of mutated DNA a person has
Uniparental Disomy
Two copies of a chromosome from one parent and zero from the other; 25% of Prader Willi Syndrome–>
Myotonic Muscular Dystrophy
CTG trinucleotide repeats in DMPK gene; Distal Weakness in hands/feet; Type 1 fibers more affected
Fragile X Syndrome
X linked trinucleotide repeats affecting the METHYLATION of FMR1 gene (fragility only describes in vitro not in vivo);
Edwards
Trisomy 18
Patau
Trisomy 13
Cri du chat
Chr 5 short arm deletion
Vitamin A def?
Deficiency causes night blindness and immune suppression
Pyruvate Dehydrogenase, Transketolase, a-Ketoglutarate Dehydrogenase, Branched-chain Ketoacid Dehydrogenase. All defective in? How to dx?
Deficiency in alcoholics Worsened if you give glucose w/o Thiamine (used for glucose metabolism)
Diagnosis of Deficiency: Increased Transketolase activity in RBC following Thiamine supplement
Hartnup disease (dec tryptophan/Neutral AA reabsorption), Carcinoid Syndrome. S/s?
Pellegra-Dermatitis, Diarrhea, Dementia/Ataxia
B6 Pyridoxal Phosphate used to make what?
Serotonin, Dopamine, NE, Epinephrine, GABA; (DA to NE requires Vit C)
Thymidine is needed for?
Allows for continuation of DNA synthesis (bypasses thymidine synthase)–> stops RBC precursor apoptosis
D and K usually present with?
Also low in iron
Decreased Vitamin K causes? (In babies)
Neonatal Hemorrhage (high suspicion if birth not at a hospital– no Vitamin K shot)–same reason why Warfarin is not used in 3rd trimester despite what they said in class
drugs that inhibit?
Alcohol:
Acetaldehyde:
Alcohol: Fomepizole
Acetaldehyde: Disulfiram
Fomepizole used to prevent toxicity w/ ethylene glycol or methanol poisoning
Vitamin E def?
Also causes hemolytic anemia with ancanthocytosis
Glucokinase function?
Glucokinase is key for glucose-sensing in the pancreatic Beta cell
Vit B1, B2, B3, B5, and Lipoic acid
Same Cofactors as alpha-Ketoglutarate Dehydrogenase
Lipoic Acid inhibitor?
arsenic:Causes vomiting, rice-water stools, and garlic-breath
Lysine and Leucine or high fat diet… are what kind of AA?
only purely ketogenic amino acids
Complex 4 of ETC?
(Cytochrome C Oxidase): Decrease protein gradient and block ATP synthesis
Uncoupling agents?
Allow H+ to pass through and consumes O2 w/o ATP synthesis–> heat generation; Aspirin. 2,4- Dinitrophenol
thermogenin in brown fat.
Myeloperoxidase color?
blue-green heme containing pigment
Fructose Intolerance defect?
Deficiency of Aldolase B (Auto rec), accumulation of Fructose-1-p causes decreased phosphate, which inhibits glycogenolysis and gluconeogenesis
Negative in fructosuria/fructose intolerance–>
glucose, instead, test for reducing sugars (included fructose)
aldolase B defect
Fructose-1-P is converted by Aldolase B to DHAP and Glyceraldehyde (triose kinase to G3P)
Galactokinase Deficiency
accumulation of Galactitol due action of Aldolase reductase on galactose
Classic Galactosemia
Defect in Galactose-1-P Uridyltransferase–>accumulation of galactitol and depletion of phosphate
E. coli Sepsis
Deficiency of Galactose-1-P Uridyltransferase
Sorbitol Dehydrogenase ?
Aldolase reductase?
Sorbitol to Fructose
Glucose is converted to osmotically active sorbitol via Aldolase Reductase
Decreased stool pH and increased breath Hydrogen
Osmotic diarrhea, bloating, flatulance. Lactase def.
Arginine and Lysine are needed for? chanrge?
Basic AA that bind the negatively charged DNA–> Histidine is also basic
Arginine forms via….?
via Arginase (produces urea and reforms ornithine)
Alpha Ketoglutarate is converted to? (Outside of the TCA cycle)
converted to Glutamate; Lactulose is used to remove excess NH4 (diarrheal that acidifies the GI)
Carbamoyl Phostphate Synthase I def?
Leads to hyperammonemia and Increased Ornithine
Ornithine Transcarbamylase Deficiency
X-linked recessive, often evident in first few days of life: Increased Orotic Acid, Decreased BUN, Hyperamonemia symptoms (Kernicterus, somnolence, vomiting, cerebral edema
Orotic Aciduria
deficiency of UMP Synthase, Megaloblastic anemia NOT treated with folate or vit B12 supplement
Malignant PKU
Deficiency in Dihydrobiopterin Reductase;
Prolactin inhibitor?
Tetrahydrobiopterin is also cofactor for Tyrosine hydroxylase–> decreased activity causes decreased DOPA, which causes decreased Dopamine, which removes inhibiton of prolactin secretion