Biochem

Question 1

Defective purine salvage due to absent HGPRT
Excess Uric acid and denovo purine synthesis
Intellectual disability, self mutilation, aggression, hyperuricemia, gout, dystonia

Answer 1

Lesch-Nyhan syndrome

X-linked, tx: allopurinol and febuxostat

Question 2

HGPRT

Answer 2

Converts hypoxanthine into IMP and guanine to GMP

Purine salvage

Question 3

Inhibits dihydroorotate dehydrogenase

Answer 3

Leflunomide (immunosuppressive DMARD arthritis)

Question 4

Mycophenolate and ribavirin

Answer 4

Inhibits IMP dehydrogenase

Question 5

Inhibits ribonucleotide reductase

Answer 5

Hydroxyurea

Question 6

6-mercaptopurine and azathioprine (prodrug)

Answer 6

Inhibits de novo purine synthesis

Question 7

Inhibits thymidylate synthase (dec deoxythymidine monophosphate)

Answer 7

5-fluorouracil

Question 8

Inhibits dihydrofolate reductase

Answer 8

Methotrexate (humans), trimethoprim (bacteria), pyrimethamine (Protozoa).

Question 9

DNA polymerase III

Answer 9

Has 5’ to 3’ synthesis and proofreads 3’ to 5’

Question 10

DNA polymerase I

Answer 10

Degrades RNA primer and replaces with DNA

Question 11

DNA mutation severity

Answer 11

Silent

Question 12

Lac operon

Answer 12

Low glucose
Inc adenylyl cyclase activity
Inc generation of cAMP from ATP
Activation of catabolite activator protein 
Inc transcription

Question 13

Nucleotide excision repair

Answer 13

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

Question 14

Base excision repair

Answer 14

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.

Question 15

Mismatch repair

Answer 15

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)

Question 16

Nonhomologous end joining

Answer 16

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

Question 17

Drugs that act on microtubules

Answer 17

Mebendazole
Griseofulvin (anti fungal)
Colchicine (anti gout)
Vincristine 
Paclitaxel
(Microtubules Get Constructed Very Poorly)

Question 18

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)

Answer 18

Kartagener syndrome (1* ciliary dyskinesia)

Question 19

Autosomal dominant polycystic kidney disease

Answer 19

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)

Question 20

Familial adenomatous polyposis

Answer 20

Colon becomes covered with adenomatous polyps after puberty. Progresses to colon cancer unless colon is resected. Mutation on chrom. 5q (APC gene)

Question 21

Familial hypercholesterolemia

Answer 21

Elevated LDL due to LDL receptor defect. Leads to severe atherosclerotic disease early in life, corneal arcus, tendon xanthomas (Achilles’ tendon).

Question 22

Hereditary hemorrhagic telangiectasia

Answer 22

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

Question 23

Hereditary spherocytosis

Answer 23

Spheroid erythrocytes due to spectrin or ankyrin defect. Hemolytic anemia, inc MCHC, inc RDW. Tx. Splenectomy. Inc LDH and unconjugated bilirubin.

Question 24

Huntington disease

Answer 24

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).

Question 25

Li-Fraumeni Syndrome

Answer 25

Abnormalities in TP53, multi malignancies at an early age. Also known as SBLA cancer syndrome (sarcoma, breast, leukemia, adrenal gland)

Question 26

Marfan syndrome

Answer 26

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.

Question 27

Multiple endocrine neoplasias (MEN)

Answer 27

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.

Question 28

Neurofibromatosis type 1

Answer 28

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.

Question 29

Neurofibromatosis type 2

Answer 29

Findings: bilateral acoustic schwannomas, juvenile cataracts, meningiomas, ependymomas. NF2 gene chrom. 22

Question 30

Tuberous sclerosis

Answer 30

Neurocutaneous disorder with multi organ system involvement, characterized by numerous benign hamartomas. Variable expression.

Question 31

Von Hipple Lindau disease

Answer 31

Disorder characterized by development of numerous tumors, both benign and malignant. Associated with deletion of VHL gene on chrom 3.

Question 32

Excess ATP and dATP
Feedback inhibition of ribonucleotide reductase
Prevent DNA synthesis and dec. lymphocyte count

Answer 32

Adenosine deaminase deficiency

Major cause of autosomal recessive SCID