zBiochem Clinical Vignettes Flashcards
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
Etoposide
- anticancer chemotherapeutics
- inhibit Euk topoisomerase II
- cut DNA cannot be rejoined so treated cell self destruct during replication
aging, CA, and telemorase
-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
Lynch Syndrome (Hereditary Non-Polyposis Colorectal Cancer–HNPCC)
- 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
Cisplatin (CDDP)
- 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
Xeroderma Pigmentosum
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.
