Correlation Boxes

Question 1

Sickle Cell Anemia

Answer 1

(Nonsense Mutation) Arises from mutation of 6th codon in allele of gene for human B-globin (HBB). Substitutes Valine for Glutamate (hydrophobic for hydrophillic). Causes it to form rigid, rod-like structures, deforming RBCs. They have poor oxygen capacity and tend to clog capillaries.

Question 2

Duchenne Muscular Dystrophy

Answer 2

Frameshift Mutation: In and out of frame leads to deletions in the dystrophin gene (nonfunctioning). OOF deletions result in having little/no expression of dystrophin, leads to muscle wasting. Inframe deletions result in truncated forms, milder form (Becker muscular dystrophy)

Question 3

I-cell Disease (Lysosomal Proteins)

Answer 3

Lack in mannose-6-phosphate signal which leads to not having any lysosomal proteins BAD. Death by 7

Question 4

Alheimer’s Disease

Answer 4

Amyloid precursor portein (APP) chops amyloid beta peptide (AB)–> misfolding leads to AB plaques in brain. hyperphosphorylation of Tau causes neurofibrillary tangles. (familial forms)
brain aging is sporadic form

Question 5

Parkinson’s Disease

Answer 5

alpha synuclein (AS) protein form into Lewy bodys in dopaminergic neurons in substantio nigra, neurons die --> reduced availibility of dopamine (familial form)
Brain aging is sporadic form

Question 6

Huntington’s disease

Answer 6

Mution in HG gene causes CAG triplet repeats (10-26 normal, 36-121 repeats =HD) Leads to polyglutamine repeats in abormal proteins which form H-bonds that misfold and aggregate. dead cells in basal ganglia lead to symptoms

Question 7

Creutzfeldt-Jakob Disease (CJD)

Answer 7

Cause by misfolding of prion proteins. Transmissible by infection (mad cow). considered a transmissible spongiform encephalopathy (TSE)

Question 8

Nucleoside Analog Inhibitors

Answer 8

ara-c, acyclovir, AZT… these drugs (for leukemia, herpes and HIV treatment) lack the 3’-OH group and inhibit DNA replication. Need to be converted into dNTPS first

Question 9

Xeroderma pigmentosum

Answer 9

Defect in nucleotide excision repair (NER) , UV from sun cause thymine dimers, which lead to the disease. Higher risk of developing melanomas and SCC due to sunlight sensitivity.

Question 10

Hereditary nonpolyposis colorectal cancer (HNCC)

Answer 10

defect in mismatch excision repair (MER), leads to an increase susceptibility to HNCC. MER nonfucntional and allows tumor development

Question 11

Cockayne Syndrome (AR)

Answer 11

defect in transcription-coupled repair (TCR) because RNA polymerase is perm. stalled at sites of damage (CANCER)… lead to cell dysfucntion and cell death (mutation in ERCC8 and ERCC6, 6 accounting for 70%) . Die in first 2 decades of life. Symp: growth retardation, skeletal abnormalities, sens. to light…

Question 12

BRCA mutation and breast cancer

Answer 12

defect in recombination pair - homologous recombination. mutations to BRCA (breast cancer susceptibility gene) 1 and 2 lead to increased risk of developing breast cancer and other cancers. they are tumor suppressor genes

Question 13

Hydrolysis of cGMP phosphodiesterase (hydrolyzes cGMP to 5’-GMP)

Answer 13

Inhibitors of cGMP PDE increase concentration of cGMP, leading to smooth muscle relaxation and vasodilation (VIAGRA)

Question 14

Nitric Oxide & smooth muscle (opp)

Answer 14

NO diffuses and activates guanylate cyclase activating cGMP, leading to smooth muscle relaxation and vasodilation (lower blood pressure)

Question 15

Cholera toxin

Answer 15

Prevents inactivation of Gsalpha due to covalent modification of alpha subunits ADP rubosylation of Arg, decreasing GTPase activity, increasing production of cAMP, opening Cl- channels, loss of Na+, H20, = diarrhea

Question 16

Pertusis

Answer 16

Prevents activation of Gialpha due to ADP ribosylation of Cys on Gi, prevents activation and dissociation of alphaGi from G protein, leads to less inhibition of AC, overprod of cAMP

Question 17

Recognition domains (RTK)

Answer 17

Adaptor proteins (GRB2,IRS1) have domains known as SH2 or PTB that recognize and bind to motifs on phospho-tyr recptors, activating signaling that need RAS

Question 18

RAS and cancer

Answer 18

mutations in RAS, GEF, and GAP leads to wide range of human cancers

Question 19

RTKS and cancer

Answer 19

RTKs are the target of pharmacological inhibitors… Used for excessive signaling from mutated/overexpressed RTks associated with cancer.