Clinical

Question 1

Inhibitors of Purine Biosynthesis

Answer 1

Glutamine analogs: block steps 2, 5, and 15; Azaserine
Folate Metabolism Inhibitors: block steps 4 and 10; comp antagonists
–PABA analog: sulfonamide
–folate analog: methotrexate (also affects TMP syn.)
–lack of folate can lead to ancephaly or spina bifidia

Question 2

Lesch-Nyhan Syndrome

Answer 2

purine overproduction, gout/kidney stones, neural problems, mental retardation, bizarre self-mutilation, X-linked

defective HGPRT

partly defective –> purine overproduction and gout only

Question 3

ADA def. aka SCID

Answer 3

lack T and B cells, gene therapy

Question 4

purine nucleoside phosphorylase def.

Answer 4

AR, immunodef., no T cells

Question 5

allopurinol

Answer 5

inhibits xanthine oxidase, blocks degradation, less uric acid

analog of hypoxanthine

Question 6

orotic aciduria

I - orotate phosphoribosyltransferase and orotidylate decarboxylase

II - orotidylate decarboxylase

Answer 6

missing 1 or both enz., give them uridine to skip blocked steps

failure to thrive, apathy, mental retardation, repeated infections, megoblastic anemia, abnormal RBCs, excessive excr. of OA, large spleen and heart

Question 7

5-Fluorouracil Derivatives

Answer 7

inhibits thymidylate synthase
suicide inhibition
F-dUMP and THF can’t detach from enzyme

Question 8

herpes and pyrimidine nucleoside salvage

Answer 8

herpes caused by a virus, has its own thymidine kinase, target it and don’t mess w/ rest of body

drug: acyclovir

Question 9

superactive PRPP synthase

Answer 9

purine overproduction and gout

Question 10

Prader-Willi Syndrome

Answer 10

4 Mb del. on chr.15q
transmitted by father
moderate mental retardation, hypogonadism, sm. hands and feet, obese

Question 11

Angelman Syndrome

Answer 11

4Mb del. on chr.15q
transmitted by mother
severe mental retardation, seizures, ataxic gait, behavior disorders

Question 12

Cystic Fibrosis and testing

Answer 12

AR, mutation in CFTR
del. of 3 bases at F508, so mutant gene is shorter by 3 bp; use PCR
ASO probe can also be used to detect mutation of F508

Question 13

Nuclear Lamina Mutations: interfere w/ lamina assembly

List diseases and any known mutations

Answer 13

Dilated cardiomyopathy; congenital lipodystrophy;
Emery-Dreifuss muscular dystrophy: AD in Lamins A/C, X in emerin
Hutchinson-Gilford Progeria: Lamin A

Question 14

DNA and drugs

Answer 14

topoisomerase II poisons - stabalizes covalent DNA top. II complex, antitumor

catalytic inhibitors - act on other steps in catalytic cycle; antineoplastic, cardioprotectors, and modulators

Question 15

mutations in mitochondrial DNA; disease examples

Answer 15

myoclonic ataxia, MERRF, MELAS, Kearns-Sayre

Parkinson’s and LHON in conjunction w/ environmental factors

Question 16

mitochondria depletion syndromes

Answer 16

• progressive disease affecting children, those treated for HIV-1 and hep.B virus infections, and young adults
• hepatic issues, muscle issues, red flag is multiorgan disturbance
• ex. Alpers, progressive external ophthalmoplegia, ataxia-neuropathy, and aging

Question 17

Example diseases for mutations in:
mismatch repair
nucleotide-excision repair

Answer 17

MR: HNPCC aka Lynch syndrome

NER: xeroderma pigmentosum

Question 18

eEF-2/GTP is inhibited by what?

Answer 18

Diphtheria toxin

Question 19

antibiotic block of initiation

Answer 19

streptomycin - distorts 30S

Question 20

antibiotic block of elongation (4 sets)

Answer 20

> tetracyclines- blocks A site
chloroamphenicol- inhibits 50S peptidyltransferase - no peptide bond
erythromycin and clindamycin - inhibits movement of ribosome by binding to 50S
puromycin - analog of tyrosinyl-tRNA; enters A site, incorporated into peptide, premature release of polypeptide; inhibits prok. and euk. protein synthesis

Question 21

Diseases of Protein Misfolding

Answer 21

prion disorders: stim. other proteins to misfold
Alzheimer’s: amyloid plaques
a-1 related emphysema: trypsin and elastase protease inhibitor fails

Question 22

Cranio-lenticulo-sultural Dysplasia

Answer 22

AR; mutation in SEC23A - part of COPII coated vesiccles that move proteins from ER to Golgi, mutation leads to dilation of ER, defects in cargo loading and budding; delayed ossification in cranial bones, sultural cataracts, facial dysmorphisms, and skeletal defects

Question 23

Grisceli Syndrome Type II

Answer 23

AR; mutation in RAB27A gene –> loss of Rab27 mRNA and protein products; episodes of uncontrolled lymphocyte activation, hypomelanosis, immunologic abnormalities, neurologic impairment

Question 24

CEDNIK: Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome

Answer 24

AR; mutation in SNAP29 - defective docking and fusion; microcephaly, neurologic impairment, psychomotor retardation, failure to thrive, facial dysmorphism, palmoplantar keratoderma, and late onset ichthyosis

Question 25

hemophilia

Answer 25

AR; mutation in ERGIC-53 or MCFD2; specific cargo not sorted into vesicles; epistaxis, menorrhagia, excessive bleeding after trauma

Question 26

choroideremia

Answer 26

XR; mutation in REP1 –> failure of Rab27A prenylation; progressive loss of vision (4% of blind pop.); choroid and retina undergo complete atrophy

Question 27

I-Cell Disease

Answer 27

def. in enz. cat. 1st step in tagging lysosomal enz. w/ M6P in Golgi; failure of lysosomal enz. incorporated into lysosomes = no lysosomal function; undegraded material collects w/in lysosomes

Question 28

Gaucher’s Disease Type 1

Answer 28

def. in glucerebrosidase - breaks down glucocerebroside into glucose and ceramide; spleen, liver, and bone sequelae; only macrophages affected –> stuffed w/ lipids; enz. replacement therapy possible but costly

Question 29

Single Gene Defects

Answer 29

come from polymorphisms or mutations in 1 gene; rare; inheritance pattern easy to ID; 2% of pop.; ex. CF

Question 30

Chromosome Disorders

Answer 30

excess or def. of genes in whole chr. or segments; 7/1000; 1/2 of 1st trimester abortions; ex. down syndrome

Question 31

Multifactorial Disorders

Answer 31

inheritance by a combo of genetic factors and in some cases non-genetic factors; recur w/in family; no certain pedigree; 5% of peds, 60% overall; ex. COPD, HTN, diabetes, Alzheimer’s

Question 32

fragile X syndrome

Answer 32

> X-linked retardation - chr. structural aberration near end of long arm of X chr.; hyperactive, marked speech delay, larger than average head circumference, long ears, slightly coarse facial appearance; Xq27.3
fragile sites - non-staining gaps, inherited codominantly, acentric fragments, chr. deletions

Question 33

Dispersed Repetitive DNA diseases (Alu and L1, deletions/insertions)

Answer 33

Alu deletions - familial hypercholesterolemia, Fabry’s dis., ADA def., and Tay-Sachs dis.
Alu insertions - neurofibromatosis and hemophilia B
L1 insertion - hemophilia A