Biochemistry Flashcards
Purines
A, G, xanthine, hypoxanthine, uric acid
Transition
Mutations that substitute a pyrimidine for a pyrimidine
Transversion
Mutations that substitute a purine for a pyrimidine or vice versa
Lesch-Nyhan syndrome
X-linked recessive. Failed purine salvage due to absence HGPRT (which converts hypoxanthine to IMP/guanine then to GMP). Thus, excess purine synthesis and uric acid production.
“Lesch Nyhan Syndrome
Lacks Nucleotide Salvage”
Dx-orange crystals in diaper, retardation, cerebral palsy, hyperuricemia
Purine nucleotide synthesis
de novo or salvage pathway. De novo for rapidly dividing cells, salvage pathway recycles from degraded nucleic acids and is the major route of synthesis in adults.
Gout
Hyperuricemia due to either overproduction or undersecretion of uric acid. Since uric acid is less soluble than hypoxanthine and xanthine, sodium urate crystals deposit in joints and soft tissue leading to arthritis
Differential dx for increased uric acid and gout
- Lesch-Nyhan
- Alcoholism
- G6P deficiency, hereditary fructose intolerance, galactose 1P uridyl transferase deficiency
Denatures DNA helix
Heat, alkaline pH, formamide, urea
Hereditary orotic aciduria
Deficiency in orotate phosphoribosyl transferase and/or OMP decarboxylase (pyrimidine metabolism). Presents with retarded growth and severe anemia. White precipitate in urine.
Nucleotide degradation
Purines: uric acid
Pyrimidine: B-amino acids, CO2, NH4+
Increased DNA methylation
decreased gene transcription
Increased histone acetylation
Increased gene transcription
Start codon
AUG
Stop codons
UGA, UAA, UAG
Holoenzyme
Core enzyme with sigma subunit that allows enzyme to recognize promoter sequences
Post-transcriptional modification
5’ capping, poly(A) tail, RNA splicing. Prevents mRNA degradation, allows translation to begin.
5’ capping
7-methyl-guanosine added to 5’ end of RNA. Stabilizes mRNA, facilitates exit from nucleus. Note-not all mRNAs have polyA tail
Poly(A) tail
40-200 adenine nt’s added to 3’ end of RNA by polyadenylate polymerase
RNA splicing
by spliceosome, which is composed of snRNPs. Binds at splice junctions flanked by GU-AG. Function-removes introns, splices together exons. Excised intron released as lariat structure
SLE
Associated with production of antibodies to host protein, including snRNPs.
Defective RNA splicing
Responsible for 15% of genetic diseases
XP
AR. Defective NER. More common in Japanese people. Cannot tolerate sunlight. First signs usu apparent at 6mo -increased pigmentation, diffuse erythema and scaling esp in light exposed areas. Second stage of disease-telangiectasias, skin atrophy, mottled irregular pigmentaiton, other characteristics of poikiloderma. Final stage-malignancies.
Protein synthesis
From N to C terminus. In three steps: initiation, elongation, termination
Post-translational modification
Trimming (e.g. in a zymogen), phosphorylation and glycosylation.