Biochem Flashcards
Defective purine salvage due to absent HGPRT
Excess Uric acid and denovo purine synthesis
Intellectual disability, self mutilation, aggression, hyperuricemia, gout, dystonia
Lesch-Nyhan syndrome
X-linked, tx: allopurinol and febuxostat
HGPRT
Converts hypoxanthine into IMP and guanine to GMP
Purine salvage
Inhibits dihydroorotate dehydrogenase
Leflunomide (immunosuppressive DMARD arthritis)
Mycophenolate and ribavirin
Inhibits IMP dehydrogenase
Inhibits ribonucleotide reductase
Hydroxyurea
6-mercaptopurine and azathioprine (prodrug)
Inhibits de novo purine synthesis
Inhibits thymidylate synthase (dec deoxythymidine monophosphate)
5-fluorouracil
Inhibits dihydrofolate reductase
Methotrexate (humans), trimethoprim (bacteria), pyrimethamine (Protozoa).
DNA polymerase III
Has 5’ to 3’ synthesis and proofreads 3’ to 5’
DNA polymerase I
Degrades RNA primer and replaces with DNA
DNA mutation severity
Silent
Lac operon
Low glucose Inc adenylyl cyclase activity Inc generation of cAMP from ATP Activation of catabolite activator protein Inc transcription
Nucleotide excision repair
Specific endonuclease release the oligonucleotide containing damaged bases, DNA polymerase and lipase fill and reseal. Repairs bulky helix-distorting lesions. Occurs in G1 phase of cell cycle.
Defective in xeroderma pigmentosum, prevents repair of pyrimidine dimers because of UV exposure
Base excision repair
Base specific glycosylase removes altered base and creates AP site. One or more nucleotides are removed by AP-endonuclease which cleaves the 5’ end. Lyase cleaves the 3’ end. DNA polymerase B fills the gap and DNA ligase seals it.
Important in deamination repair.
Mismatch repair
Newly synthesized strand is recognized, mismatch nucleotides are removed, and the gap is filled and resealed. Occurs in G2 phase
Defective in hereditary nonpolyposis colorectal cancer (HNPCC)
Nonhomologous end joining
Brings together 2 ends of DNA fragments to repair double stranded breaks. No requirement for homologous. Some DNA lost.
Mutated in ataxia telangiectasia, fanconi anemia
Drugs that act on microtubules
Mebendazole Griseofulvin (anti fungal) Colchicine (anti gout) Vincristine Paclitaxel (Microtubules Get Constructed Very Poorly)
Immotile cilia due to a dynein arm defect.
Results in male and female infertility due to immotile sperm and dysfunctional Fallopian tube cilia. Inc risk of ectopic pregnancy. Can cause bronchiectasis, recurrent sinusitis, and situs inversus (dextrocardia)
Kartagener syndrome (1* ciliary dyskinesia)
Autosomal dominant polycystic kidney disease
Bilateral massive enlargement of kidney due to large cysts. 85% of cases due to mutation in PKD1 (chrom. 16) remainder due to mutation in PKD2 (chrom. 4)
Familial adenomatous polyposis
Colon becomes covered with adenomatous polyps after puberty. Progresses to colon cancer unless colon is resected. Mutation on chrom. 5q (APC gene)
Familial hypercholesterolemia
Elevated LDL due to LDL receptor defect. Leads to severe atherosclerotic disease early in life, corneal arcus, tendon xanthomas (Achilles’ tendon).
Hereditary hemorrhagic telangiectasia
Inherited disorder of blood vessels. Findings: branching skin lesions (telangiectasias), recurrent epistaxis, skin discolorations, arteriovenous malformations, GI bleeding, hematuria. Also known as, Osler Weber Rendu Syndrome
Hereditary spherocytosis
Spheroid erythrocytes due to spectrin or ankyrin defect. Hemolytic anemia, inc MCHC, inc RDW. Tx. Splenectomy. Inc LDH and unconjugated bilirubin.
Huntington disease
Findings: depression, progressive dementia, choreiform movements, and caudate atrophy. Inc dopamine, dec GABA, dec ACh in the brain. Gene on chrom. 4 (CAG) (inc. histone deacetylation).
Li-Fraumeni Syndrome
Abnormalities in TP53, multi malignancies at an early age. Also known as SBLA cancer syndrome (sarcoma, breast, leukemia, adrenal gland)
Marfan syndrome
FBN1 gene on chrom. 15. Defective fibrillin, connective tissue disorder, affecting skeleton, heart, and eyes. Findings: tall with long extremities, pectus excavatum, hypermobile joints, and long tapering fingers and toes. Aortic incompetence and dissecting aortic aneurysms, floppy mitral valve. Subluxation of lens.
Multiple endocrine neoplasias (MEN)
Several distinct syndrome characterized by familial tumors of endocrine glands, including those of the pancreas, parathyroid, pituitary, thyroid, and adrenal medulla. MEN1ass. with MEN1 gene. MEN2A and 2B are ass. with RET gene.
Neurofibromatosis type 1
Neurocutaneous disorder characterized by cafe-au-lait spots, cutaneous neurofibromas, optic gliomas, pheochromocytomas, Lisch nodules. Autosomal dominant, variable expression. Mutation in the NF1 gene chrom. 17.
Neurofibromatosis type 2
Findings: bilateral acoustic schwannomas, juvenile cataracts, meningiomas, ependymomas. NF2 gene chrom. 22
Tuberous sclerosis
Neurocutaneous disorder with multi organ system involvement, characterized by numerous benign hamartomas. Variable expression.
Von Hipple Lindau disease
Disorder characterized by development of numerous tumors, both benign and malignant. Associated with deletion of VHL gene on chrom 3.
Excess ATP and dATP
Feedback inhibition of ribonucleotide reductase
Prevent DNA synthesis and dec. lymphocyte count
Adenosine deaminase deficiency
Major cause of autosomal recessive SCID
