Biochemistry Flashcards
Neurofibromatosis I
AD disorder. Cafe au lait spots, neurofibromas, Lisch nodules (iris hamartomas), skeletal abnormalities. NF1 on chromosome 17.
Pompe’s disease
Glycogen storage disease. Deficiency in lysosomal alpha-1,4-glucosidase. Cardiomegaly, weakness, hypotonia. Early death due to cardiorespiratory failure.
Alkaptonuria
Congenital deficiency of homogentisic acid oxidase in tyrosine degradation pathway. Homogentisic acid builds up and polymerizes to form alkapton bodies which deposit to cause dark urine and dark cartilage. May have arthralgias and decreased joint mobility.
Angiotensin effect on efferent arteriole of kidney
Binds to Gq, activating phospholipase C and cause constriction of the efferent.
Cyanide poisoning
Causes HA, confusion, seizures, vomiting, cherry red lips, cyanosis. Binds with high affinity to mitochondrial cytochrome oxidase, inhibiting the electron transport chain.
Maple syrup urine disease
Causes hypoglycemia during fasting due to inability to metabolize leucine, isoleucine, and valine.
Neurofibromatosis type II
Audosomal dominant mutation on chromosome 22. Acoustic schwannomas, meningiomas, gliomas, neurofibromas, juvenile cataracts.
Homocystinuria
Inborn error of methionine metabolism. Diagnosed by elevated homocysteine in blood and urine. AR mutation. Normal at birth. Clinically manifests as failure to thrive and developmental delay. Can present with subluxation of ocular lens. Usually marfanoid habitus with scoliosis, fair complexion, blue eyes, flushing of cheeks. Increased risk of osteoporosis and thromboembolism, May respond to pyridoxine (vitamin B6) which is a cofactor for the deficient enzyme.
Benign fructosuria
Deficiency of fructokinase which converts fructose to fructose-1-phosphate. Asympomatic because hexokinase takes over.
Metachromatic leukodystrophy
AR disease caused by deficiency of lysosomal arylsulfatase A. Demyelination in central and peripheral nerves. Accumulation of cerebroside sulfate, which appears brown when stained with toluidine blue.
Heterochromatin vs euchromatin
Heterochromatin is condensed and transcriptionally inactive. Euchromatin is transcriptionally active.
Histone methylation vs acetylation
Methylation represses transcription; histone relaxes coiling and allows for transcription. (Methylation - mute, acetylation - active)
Purines vs pyrimidines
Purines: two rings, A and G
Pyrimidines: one ring, C, T, and U
Purine synthesis
Sugar + phosphate –> PRPP –> IMP –> AMP and GMP
Pyrimidine synthesis
Glutamine + CO2 –> carbamoyl phosphate –> orotic acid –> UMP
Molecular basis of SCID
AR adenosine deaminase deficiency. Excess ATP imbalances nucleotide pool –> feedback inhibition of ribonucleotide reductase –> inhibition of DNA synthesis
DNA topoisomerase
Creates single or double stranded breaks in helix to add or remove supercoils. Drug target of fluoroquinolones.
DNA polymerase I
Degrades RNA primer and replaces it with DNA. 5’ to 3’ synthesis. 3’ to 5’ and 5’ to 3’ exonuclease activity.
Transition vs transversion mutation
Transition: purine to purein or pyrimidine to pyrimidine
Transversion: purine to pyrimidine or vice versa
Lac operon
Activated in e coli when glucose is absent but lactose is available. Low glucose activates activator protein and high lactose unbinds repressor allowing for transcription.
When different mechanisms of DNA repair are used
Nucleotide excision repair: bulky distoring lesions, G1 phase, defective in xeroderma pigmentosum
Base excision repair: repair of spontaneous/toxic deamination; throughout cell cycle
Mismatch repair: G2 phase, defective in Lynch syndrome (hereditary nonpolyposis colorectal cancer)
Nonhomologous end joining
Some DNA lost; mutated in ataxia telangiectasia and Fanconi anemia
Protein synthesis direction
N to C
Promotor
Site where RNA polymerase II and other TFs bind to DNA in trnascription
Eukaryotic RNA polymerases: what they make
RNA poly I: rRNA
RNA poly II: mRNA, inhibited by alpha-aminitin in mushrooms
RNA poly III: tRNA
inhibited by actinomycin D
Rifampin inhibits RNA poly in prokaryotes
Process of pre-mRNA splicing
Primary transcript combines with snRNPs to form spliceosome.
Lariat shaped intermediate formed.
Lariat released to remove intron and join two ends
anti-smith antibodies
antibodies against the spliceosomal snRNPs. Specific for SLE.
Thiamine functions
Cofactor for:
- pyruvate dehydrogenase
- alpha-ketoglutarate dehydrogenase in TCA cycle
- transketolase in HMP shunt
Thiamine deficiency
Triad of opthalmoplegia, ataxia, confusion. Focal hemorrhage and necrosis in mammilart bodies and PAG.
Cyanide poisoning
Presents with breathing difficulty, palpitations/tachycardia, headache, flushing, N/V, confusion, weakness. Antidote is nitrites.
Antibodies present in rheumatoid arthritis
Rheumatoid factor: low specificity
Anti-citrullinated peptides (anti-CCP): highly specific
Niemann-Pick disease
AR disease. Ashkenazi Jeish descent. Deficiency of sphingomyelinase causes sphingomyelin to accumulate in phagocytes. Foamy histiocytes accumulate in liver, spleen, skin. Neurologic degeneration due to sphingomyelin deposition in CNS. Progresses to hypotonia and blindness. May see cherry red spot in eye and hepatosplenomegaly on exam. Death by age 3.
Hereditary fructose intolerance
Caused by aldolase B deficiency. Present when fructose-containing foods introduced with vomiting, hypoglycemia 20-30mins after eating fructose. Can also present with failure to thrive, jaundice, hepatomegaly
Impaired beta-oxidation
Causes hypoglycemia after prolonged fasting with inappropriately low ketone bodies. Most commonly due to deficiency of acyl-coA dehydrogenase.
