zBiochem Clinical Vignettes Flashcards
(29 cards)
Ehlers-Danlos Syndrome
-abnormaliites of skin, ligaments, internal organs
-skin stretchs easily
-joint laxity
-
Osteogenesis
- abnormal collagen type I
- bone fragile and readily fracture
scurvey
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
-
Marfan’s syndrome
- defect in protein fibrillin
- tall stature with arachnodactyly
- mitral valve prolapse, lens dislocation
DM
- 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
Phenylketonria PKU
- 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
5-FU (5-fluorouricil)
ddI (dideoxyinosine)
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
creatine kinase (CK) =MB isozyme in the heart muscle
- 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
sicke cell anemia
- 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
Hemoglobin wayne
-deletion of a base cause frameshift produce wrong sequence of aa
thalassemias
-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
Cancer
-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
Rifampicin
- inhbit initiation of prokaryotic RNA synthesis
- tx TB
alpha-amanitin
- derived frmo poisonous mushroom inhibit Euk RNA polymerases
- cause GI problems result in death
compounds that inhibit protein synthesis
- streptomycin
- tetracylcine
- chloramphenicol
- erythromycin
- -above inhibit protein synthesis on prok (70S) ribosomes, tx infections
- mitochondria contain 70S ribosomes also inhibit mito protein synthesis
Intravenous Fructose Load
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
hereditary fructose intolerance
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
galactosemia
classical
nonclassical
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
glycolysis & diabetes
- Type I
- Type II (3 subtypes)
-
Non-alcoholic steatohepatitis (NASH)
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)
cholera
-
pertussis
-
anti-retroviral dideoxynucleosides
- 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
Quinolones: ciprofloxcin
-target bacterial topoisomerase only, lead to bact cell death
