Biochem Clinical Vignettes

Question 1

Ehlers-Danlos Syndrome

Answer 1

-abnormaliites of skin, ligaments, internal organs
-skin stretchs easily
-joint laxity
-

Question 2

Osteogenesis

Answer 2

• abnormal collagen type I

- bone fragile and readily fracture

Question 3

scurvey

Answer 3

vit C déficience
-hydroxylation of proline residues decrease
-unstable collagen produced
-bone, teeth, blood vessels, other rich collagen structure abnormal
-bleeding gums & poor wound healing
-

Question 4

Marfan’s syndrome

Answer 4

• defect in protein fibrillin
• tall stature with arachnodactyly
• mitral valve prolapse, lens dislocation

Question 5

DM

Answer 5

• decrease secretion of insulin or resistance of tissues to insulin action
• hyperglycemia/ hypoglycemia
• plasma contain antibodies–autoimmunity–to islet cell of pancreas that produce insuline

Question 6

Phenylketonria PKU

Answer 6

• 1/10,000 births in asian and whites
• enzyme phenylalanine hydroxylase converts phenylalanine to tyrosine is deficient
• accumulate phenylalanine but tyrosine is essential
• mental retardation from metabolic derangement
• lactase deficiency–>not digested and metabolize by bact.
• bloating, cramps, watery diarrhea

Question 7

5-FU (5-fluorouricil)

ddI (dideoxyinosine)

Answer 7

chemotherapeutic agent to inhibit proliferation of cancer cells
-inhibit enzyme thymidylate synthetase (convert dUMP to dTMP–>provide thymine for DNA synthesis

• ddI
• chain terminator in DNA synthesis, tx HIV

Question 8

creatine kinase (CK) =MB isozyme in the heart muscle

Answer 8

• heart attack, MB enzyme release into blood when cells are injured
• extent of damage and rate of recovery can be estimated by measuring level of CK and its MB enzyme

Question 9

sicke cell anemia

Answer 9

• point mutation: missense
• valine replaced glutamate at position 6 in beta-globin chain
• hydrophobic interaction btw these valine residues on different hgb molecules cause polymerization of sickle cell hgb,
• alter RBC shape result in hemolysis

Question 10

Hemoglobin wayne

Answer 10

-deletion of a base cause frameshift produce wrong sequence of aa

Question 11

thalassemias

Answer 11

-a group of hemolytic anemias
-mutation affects all step of RNA metabolism
substitution in TATA box decrease promoter function
-mutation of splice junctions create alternative splice sites
-change in polyadenylation site result in incorrect hnRNA and abnormal mRNA degraded
-change CAG to TAG produce stop codon cause shortening, nonfunctional protein
-mutations cause insufficient quantities of glob in to be produced, anemia result

Question 12

Cancer

Answer 12

-cell nonresponsive to normal restrainst on growth
-cause: radiation, chemcials, viruses
-damage DNA
-produce mutation
-burns in smoke produce benzo(a)pyrene –>lung cancer
-UV produce pyrimidine dimers in DNA skin cancer, pronounced in people with xeroderma pigmentosum because DNA repair not working
oncogenes vs. proto-oncogenes
-decrease expression of suppressor genes

CA drug 5-FU (flurouracil) interferes with DNA synthesis prevent conversion of dUMP tp dTMP
-methotrexate prevent formation of tetrahydrofolate from its more oxidized precursors–>DNA & RNA synthesis inhibited

Question 13

Rifampicin

Answer 13

• inhbit initiation of prokaryotic RNA synthesis

- tx TB

Question 14

alpha-amanitin

Answer 14

• derived frmo poisonous mushroom inhibit Euk RNA polymerases
• cause GI problems result in death

Question 15

compounds that inhibit protein synthesis

Answer 15

• streptomycin
• tetracylcine
• chloramphenicol
• erythromycin
• -above inhibit protein synthesis on prok (70S) ribosomes, tx infections
• mitochondria contain 70S ribosomes also inhibit mito protein synthesis

Question 16

Intravenous Fructose Load

Answer 16

Rapid deleption of Pi (inorganic phosphate) and energy sources
-fructokinase very active, fructose transprot into liver rapid, F1P accumulate
-ATP converted to ADP by fructokinase, triose kinase
-Pi used to convert ADP to ATP by oxidative phosphorylation, leading to Pi depletion (trapped in F1P)
elevelated levels of uric acid
-uric acid end product of purine metabolism
0drop in Pi and increase AMP level (2ADP–>ATP, AMP) trigger purine degradation
lactic acidosis

Question 17

hereditary fructose intolerance

Answer 17

defect F1P aldolase
-aldolase B in liver & kidney
aldolase A & C in other tissues
liver still splits F1,6BP with residual B activity and low levels of A form of aldolase
-aldolase A dont split F1P
-hypoglemia results from increase F1P
-glycogen degradation inhibted due to F1P inhibition of glycogen phosphorylase (normal product G1P) and sequestration of phosphate in F1P
-gluconeogenesis impaired due to low activity of aldolase
-lactic acidosis does occur (due to inhibition of gluconeogenesis, lack ATP, uric acid blocking lactate release from blood into kidney
-patients avoid fructose and are fine

Question 18

galactosemia
classical
nonclassical

Answer 18

classical

• lack gal1-P uridylyl transferase; gets accumulated of galactose and galactitol lead to cataract formation, irreversibke mental retardation
• hypoglycemia result from galactose-1P inhibition of phosphoglucomutase (normal substrate Glu-1-P

nonclassical
-loss of galactokinase
cataract formation occurs due to galactitol accumulation but not hypoglycemia or mental retardation
-treat by removing from diet

Question 19

glycolysis & diabetes

• Type I
• Type II (3 subtypes)

Answer 19

-

Question 20

Non-alcoholic steatohepatitis (NASH)

Answer 20

when glucagon predominates, PFK2 and PK are phosphorylated and inhibited (liver just see glucagon)

• gluconeogenesis is stimualted and glucose is exported
• glucokinase forces glycolysis forward and liver makes fat from glucose (due to high blood glucose levels–>disease
• liver also metabolizes fat (liver confused)

Question 21

cholera

Answer 21

-

Question 22

pertussis

Answer 22

-

Question 23

anti-retroviral dideoxynucleosides

Answer 23

• carry no 2’ or 3’ –OH group
• incorporate into growing DNA and gets terminated inhibite reverse transcriptase
• AZT (zidovudine) & 3TC (lamivudine)= combivir= combination drug for HIV include inhibitor of other HIV life cycle

Question 24

Quinolones: ciprofloxcin

Answer 24

-target bacterial topoisomerase only, lead to bact cell death

Question 25

Etoposide

Answer 25

• anticancer chemotherapeutics
• inhibit Euk topoisomerase II
• cut DNA cannot be rejoined so treated cell self destruct during replication

Question 26

aging, CA, and telemorase

Answer 26

-fully differentiated adult cells lost expression of telomerase–aging may be one consequence of telomerase inactivity since cells will die through telomere loss even if stimulated to divide

• unschedule expression of telemorase is typically found in tumors linked to immortal character
• telomerase essential to healthy dividing cells, immune cells, RBC, germ cells

-treatment with telemorase inhibitors to inhibt tumor growth would have serious side effects but beneficial

Question 27

Lynch Syndrome (Hereditary Non-Polyposis Colorectal Cancer–HNPCC)

Answer 27

• colon caner is due to DNA mismatched repair gene linked genetic defect (one of the MutS or MutL related gene
• acts as anutosomal dominant–disease onset normally occurs before age 50

Question 28

Cisplatin (CDDP)

Answer 28

• is a DNA cross linking agent–damage DNA causing stand breaks during DNA replication
• therapeutic value–> use 1st line therapy aginst tumors by taking advanatge of rapid proliferation of many tumors

more DNA adduct=better survival

Question 29

Xeroderma Pigmentosum

Answer 29

sensitivity to UV radiation, alkylation

susceptible to carcinomas an melanomas cancer

skin and eye photosensitivity. neurological abnormality in certain types

Thymine dimer–A pair of abnormally chemically bonded adjacent thymine bases in DNA, resulting from damage by ultra-violet irradiation. The cellular processes that repair this lesion often make errors that create mutations.