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103 Cards in this Set
- Front
- Back
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What gives DNA a negative charge?
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Phosphate
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What gives DNA a positive charge?
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Lysine and Argenine
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What does methylation do to DNA?
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Makes DNA mute
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What is hypermethylation?
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Inactivates transcription of DNA
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What is histone acetylation?
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Makes DNA active
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Which bonds increase the melting temp of DNA?
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G-C bonds (contain 3 H-bonds)
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Amino acids needed for purine synthesis?
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Glycine, Aspartate, Glutamine
(also need THF4) |
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Rate limiting enzyme for purines?
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Glutamine PRPP aminotransferease
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Rate limiting enzyme for pyrimidines?
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CPS II
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What is Orotic Aciduria?
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Inability to convert orotic acid to UMP due to defect in Orotic Acid Phosphoribosyltransferase or Orotidine 5'-phosphate decarboxylase.
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What are the symptoms of Orotic Aciduria?
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Megaloblastic Anemia (does not improve w/folate or B12)
Failure to Thrive Orotic Acid in Urine (No increase in NH4) |
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Treatment for Orotic Aciduria?
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Oral Uridine Administration
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Hydroxyurea MOA?
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Inhibits Ribonucleotide reductase
(used for Sickle Cell Pts) |
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Difference b/w CPSI and CPS II
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CPS I - mitochondria, urea cycle, Nitrogen for NH4
CPS II - Cytosol, Pyrimidine Synthesis, Nitrogen from Glutamine |
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Adenosine Deaminase deficiencey
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SCID
Excess ATP causes feedback inhibition of Ribonucleotide Reductase--> prevents DNA synthesis-->decreased lympocytes |
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Triad Symptoms of SCID?
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Failure to thrive, Severe Recurrent Infections, Chronic Diarrhea
(absence of thymic shadow and decrease lymphocyte count) |
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Lesch-Nyhan Syndrome
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Defective Purine salvage pathway due to lack of HGPRT which converts hypoxanthine to IMP and Guanine to GMP
Excess Uric acid production |
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Findings of Lesch-Nyhan Syndrome?
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Retardation, self-mutilation, agression, hyperuricemia, gout, choreoathetosis
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Nonsense mutation?
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Early stop codon
"STOP the nonsense" |
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Missense mutation?
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Changed amino acid
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Frameshift mutation?
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Leads to misreading of all nucleotides downstream.
Can cause a truncated, non functional protein |
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Silent mutation?
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Change in base in 3rd position
tRNA Wobble effect |
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DNA topoisomerases function?
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Create nick in helix to relieve supercoil
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DNA polymerase Alpha function?
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Replicates lagging strand & synthesizes RNA primer
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DNA polymerase Beta & Epsilon function?
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Repair DNA
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DNA polymerase Gamma function?
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Replicate mitochondrial DNA
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DNA polymerase Delta function?
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Replicate leading strand DNA
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Xeroderma Pigmentosum defect?
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Defect in nucleotide excision repair, which prevents repair of Thymidine dimers due to UV light exposure.
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What type of DNA repair mechanism is defective in HNPCC?
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Mismatch Repair
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What type of DNA repair mechanism is defective in Ataxia Telangiectasia?
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Nonhomologous end joining
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Types of RNA
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rRNA (polymerase 1) most abundant
mRNA (polymerase 2) longest type tRNA (polymerase 3) smallest type |
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Where are tRNA and mRNA synthesized?
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Nucleoplasm
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Where is rRNA synthesized?
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Nucleolus
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Alpha Amanitin function?
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Mushroom toxin that can inhibit RNA Polymerase II.
Causes liver failure. |
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What cells is ptotein synthesis completed in?
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Fibroblasts, Hepatocytes, Plasma Cells
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Stable/Quiescent Cells?
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Lymphocytes and Hepatocytes
Enter G1 when stimulated |
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Permanent Cells?
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Neurons, skeletal & cardiac muscle, RBC's
Divide from stem cells |
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Which Amino Acids are modified by the Golgi?
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Serine, Threonine, Asparagine, Tyronine
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What is COP I?
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Retrograde trafficking protein.
From Golgi-->ER |
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What is COP II?
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Anterograde trafficking protein
From RER-->cis-Golgi |
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What is I-cell Disease?
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Failure of addition of mannose-6-phosphate to lysosome proteins
Enzymes are secreted outside of the cell instead of lysosome. |
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What is the defect in Chediak-Higashi syndrome?
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Decreased fusion of phagososmes and lysosomes
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What is the triad of symptoms in Chediak-Higashi?
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Pyogenic Infections
Partial Albinism Peripheral Neuropathy |
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Kartagener's Syndrome?
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Immotile cilia, dynenin arm defect
Results in infertility, bronchiectasis, and recurrent sinusitis Associated w/Situs Inversus |
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Collagen Synthesis?
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Synthesis in RER - Preprocollagen- Need Glysine
Hydroxylation (ER) - need Vitamin C Glycosylation (ER) - formation of procollagen (tripple helix) Exocytosis Proteolytic Processing - forms tropocollagen Cross Linking |
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Osteogenesis Imperfecta?
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Type I collagen defect (AD)
Multiple Fractures Blue Sclerae Hearing Loss Dental Imperfection (lack of dentin) |
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Ehlers-Danlos Syndrome?
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Type III Collagen Defect (AD/AR)
Hyperextensible Skin Tendency to Bleed Hypermobile Joints |
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Alport Syndrome?
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Type IV Collagen Defect
X-linked Recessive Nephritis Deafness Ocular Disturbances |
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What is Pleiotropy?
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One gene has more than 1 effect on a person's phenotype.
Ex. PKU |
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Dominant Negative Mutation?
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Heterozygote produces a non-functional protein that prevents the normal gene product from functioning.
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What is Heteroplasmy?
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Normal and mutated mtDNA
Variable expression in mitochondrial inherited disease |
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What is Hypophosphatemic Rickets?
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Increase phosphate wasting at proximal tubule.
X-linked Dominant |
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Mitochondrial Myopathies?
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Leber's Hereditary Optic Neuropathy
Myoclonic Epilepsy Mitochondrial Encephalopathy "Ragged Red Fibers" on microscopy |
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Achondroplasia
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Defect in FGF Receptor 3 (AD)
Dwarfism Short extremities, normal head and trunk Advanced Paternal Age |
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ADPKD
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Bilateral (AD)
Mutation in PKD1 (Ch. 16) Associated w/Polycystic Liver Disease, Berry Aneurysms, Mitral Valve Prolapse |
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Familial Adenomatous Polyposis
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Colon covered w/adenomatous polyps after puberty (AD)
APC Gene (Ch. 5) progresses to Colon CA unless resected |
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Familial Hypercholesterolemia
(Hyperlipidemia Type IIa) |
Elevated LDL due to defective or absent receptor. (AD)
Atherscleotic Disease Tendon Xanthomas MI before 20y/o |
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Hereditary Hemorrhagic Telangiectasia
(Osler-Weber-Rendu Syndrome) |
Disorder of BV's (AD)
Telengectasia Recurrent Epistaxis Skin Discoloration Arteriovenous Malformations |
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Hereditary Spherocytosis
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Spectin or Ankyrin Defect (AD)
Hemolytic Anemia Splenectomy is curative Dx w/osmotic fragility test |
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Huntington's Disease
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Decreased GABA & Ach (AD)
Affects Basal Ganglia CAG Repeat (Ch. 4) |
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Marfan's Syndrome
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Fibrillin Gene Mutation (AD)
Long Extremeties Cystic Medial Necrosis of Aorta Floppy Mitral Valve Sublexation of lenses Berry Aneurysms |
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MEN
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Family tumors of endocrine glands (AD)
MEN 2A and 2B associated w/ret gene |
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NFT 1
(von Recklinghausen's Disease) |
Cafe-au-lait spots (AD)
neural tumors Lisch nodules Ch. 17 (long arm) |
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NFT 2
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Bilateral acoustic schwannomas (AD)
Juvenille Cataracts Ch. 22 |
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Tuberous Sclerosis
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"Ash leaf spots" on skin (AD)
Cortical/retinal harmartomas Seizures, MR Cardiac Rhabdomyomas, Astrocytomas, Renal Angiolypomas Imcomplete Penetrance |
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von Hippel-Lindau Disease
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Deletion of VHL gene on Ch. 3 (AD)
Constituative activation of HIF transcription factor & activation of angiogenic growth factors Bilateral Renal Cell Carcinoma |
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Fragile X Syndrome
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X-linked
Xtra-large testes, jaws, & ears FMR1 Gene #1 Cause of inherited MR |
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Trinucleotide Repeat Disorders
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Fragile X (CGG)
Friedricks Ataxia (CAA) Huntington's (CAG) Mytotonic Dystrophy (CTG) |
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Cri-du-chat Syndrome
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Microdeletion of short arm of Ch.5
VSD Microcephaly MR |
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Williams Syndrome
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Microdeletion of long arm of Ch. 7
"Elfin facies" MR Hypercalcemia Extreme friendliness w/strangers |
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Pyruvate Dehydrogenase Deficiency
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Causes Neurologic Defects
Increase Intake of Ketogenic Amines (Lysine & Leucine) or Increase High fat content foods |
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G6PD Deficiency
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Decreased NADPH in RBC's leads to hemolytic Anemia (AR)
Poor RBC defense to oxidizing agents Heinz Bodies & Bite Cells Fava Beans, Sulfonamides, Primaqquine, & Anti-Tb drugs precipitate problems |
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Essential Fructosuria
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Deficiency in Fructokinase (AR)
Fructose appears in blood & urine |
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Fructose Intolerance
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Deficiency in Aldolase B (AR)
Fructose-1-phosphate accumulates Decrease in available phosphate Inhibition of glycongenolysis & gluconeogenesis Hypoclycemia, jaundice, cirrhosis, Vomiting Tx = decrease fructose & sucrose |
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Galactokinase Deficiency
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Defeciency in Galactokinase (AR)
Galactose in Blood/Urine Failure to develop social smile, inability to track objects, infantile cataracts |
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Classic Galactosemia
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Deficiency in Galactose-1-phosphate Uridyltransferase (AR)
Failure to thrive, jaundice, infantile cataracts, Hepatomegaly, MR Exclude galactose and lactose from diet |
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What amino acids help w/nuclear localization signals?
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Lysine, Argenine, Proline
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What helps to trap ammonia in the gut?
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Lactulose
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Ornithine Transcarbamoylase Deficiency
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X-linked Recessive
Body can't eliminate ammonia Orotic Acid in blood in urine Hyperammonemia Decreased BUN Most common urea cycle disorder |
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Phenylketonuria (PKU)
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Decreased Phenalanine Hydroxylase or decreased tetrahydrobiopterin cofactor
MR, Growth Retardation, Seizures, fair skin, eczema, Musty Body Odor Tx= Decrease Phenylalanine & increase tyrosine |
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Alkaptonuria
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Deficiency of Homogentisic Acid Oxidase (AR)
Dark Connective tissue, Brown sclera, Black urine, Arthralgias |
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Albinism
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Deficiency in Tyrosinase (AR)
or Defective Tyrosine Transporters Can result from lack of migration of neural crest cells |
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Homocystinuria Causes
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AR
Cystathionine Synthase Deficiency or Decreased Affinity of cystathionine synthase for B6 or Decreased Homocysteine Methyltransferase |
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Homocystinuria Effects?
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MR, osteoporosis, in homocysteine in urine, lens subluxation, atherosclerosis
Tx= Decrease Methionine, Increase B12, B6, Folate, & Cysteine |
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Cystinuria
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Defect of renal tubular transporter for cysteine, ornithine, lysine, & argenine
Can cause kidney stones Tx=Acetazolamide to alkalinize urine |
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Maple Syrup Urine Disease
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Blocked Degradation of branched chain amino acids (Ile, Leu, Val)
Decreased Alpha-Keotacid dehydrogenase CNS defects, MR, and death |
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Hartnup Disease
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Defective Neutral Amino acid transporter on renal and intestinal epithelial cells
Tryptophan excretion in urine Leads to Pellagra (Dermatitis, Diarrhea, Deentia) |
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VonGirke's Disease
(Type I) |
Severe fasting hypoglycemia, Increased glycogen in liver, increase blood lactate, increase uric acid, hepatomegaly
Deficiency: Glucose-6-phosphatase |
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Pompe's Disease
(Type II) |
Cardiomegaly
Deficiency: Lysossomal Alpha-1,4-glucosidase (acid maltase) Pompe's trashes the heart, liver, and muscle |
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Cori's Disease
(Type III) |
Milder form of Type I w/ normal blood lactate levels
Deficiency: Debranching enzyme (alpha-1,6-glucosidase) Gluconeogenesis is intact |
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McArdle's Disease
(Type V) |
Increased glycogen in muscle, but cant break it down
Painful cramps, myoglobinuria, rhabdomyolysis Defect: Skeletal muscle glycogen phosphorylase |
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Adult Pompe's
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Diaphragm Weakness and respiratory failure
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Fabry's Disease
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Peripheral Neuropathy hands/feet (XR)
Angiokeratomas Progressive renal failure Deficiency: Alpha glactosidase A Accumulate: Ceramide trihexoside |
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Gaucher's Disease
(Most Common) |
HSM, Aseptic necrosis of femur, Gaucher's cells (look like crumpled tissue paper)
(AR) Deficiency: Glucocerbrosidase Accumulate: Glucocerboside |
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Neimann-Pick Disease
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Progressive neurodegeneration, HSM, cherry red spot on macula, foam cells, Early Death (AR)
Deficiency: Sphingomyelinase Accumulate: Sphingomyelin |
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Tay-Sachs Disease
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Progressive neurodegeneration, lysosomes w/onion skin, cherry red spot on macula, foam cells, Early Death (AR)
Deficiency: Hexosaminidase A Accumulate: GM2 ganglioside |
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Krabbe's Disease
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Peripheral Neruopathy, developmental delay, optic atrophy, globoid cells, Early Death (AR)
Deficiency: Beta-galactocerbrosidase Accumulate: Galactocerbroside |
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Metachromic Leukodystrophy
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Central and peripheral demyelmination w/ataxia & dementia (AR)
Deficiency: Arylsulfatase A Accumulate: Cerebroside Sulfate |
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Hurler's Syndrome
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Gargoylism, Airway Obstruction, Corneal Clouding, HSM, & MR (AR)
Deficiency: Alpha-L-iduronidase Accumulate: Heparin Sulfate & Dermatan Sulfate |
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Scheie's Syndrome
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Milder form of Hurler's syndrome
Conreal clouding No MR |
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Hunter's Syndrome
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Mild Hurler's + agressive behavior (XR)
No corneal clouding MR Deficiency: Iduronate Sulfatase Accumulate: heparin & dermatan sulfate |
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Abetalipoproteinemia
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Inability to synthesize lipoproteins Deficiencies in apoB-100 & apoB-48 (AR)
Accumulation w/in enterocytes Inability to export lipid as chylomicrons |
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Abetalipoproteinemia Signs
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Failure to thrive, steatorrhea, acanthocytosis (spiky plasma membrane of RBC's), Ataxia, night blindness
Tx=Vitamin E |
