Exam 2 Review Flashcards
How does diphtheria toxin inhibit eukaryotic translation?
inactivates GTP bound EF interfering with ribosome translocation
Which step in the TCA cycle forms GTP by substrate phosphorylation?
Succinyl CoA to succinate by succinate thiokinase (succinate synthetase)
also forms CoA
What is cystinuria?
Defective transport of dimeric cystine and dibasic AAs Arg, Lys and ornithine
formation of cystine crystals in kidney, renal colic, abdominal pain, kidney stones
What is ADA deficiency?
Second most common form of SCID
Leads to increased adenosine levels and thus increased dATP as well as decreased dNDP/NTP which impairs DNA synthesis and leads to a compromised immune system
What is gout?
Characterized by high levels of uric acid in the blood
Results in extremely painful deposits of Na rate in the joints
Diets rich in purines can trigger episodes
tx = allopurinol which inhibits xanthine oxidase
What regulates citrate synthase?
Activated by insulin, acetyl CoA an OAA
Inhibited by citrate, ATP, succinyl CoA and NADH
What is the chemiosmosis hypothesis?
Coupling of the transfer of e- with phosphorylation of ADP to form ATP
What is the signal sequence for mitochondrial proteins?
N terminal hydrophobic alpha helix
How does rotenone effect oxphos?
Inhibits complex I and prevents e- transfer to ubiquinone (coenzyme Q)
What is Lesch Nyann syndrome?
Defects in HGPRT in purine salvage pathway
Rare form of hyperuricemia leading to gout, urate kidney stones, poor muscle control, mental retardation and tendency for self mutilation
What is the signal sequence for membrane proteins?
N terminal apolar sequences
What activates isocitrate dehydrogenase?
ADP and Ca2+
What role does xanthine oxidase play in purine catabolism?
Hypoxanthine -> xanthine -> uric acid
Target for gout tx
What is the signal sequence for ER lumen proteins?
KDEL
What is the signal sequence for lysosomal proteins?
mannose 6 phosphate
Describe pyrimidine catabolism
Converted to glucogenic or ketogenic compounds
Uracil/cytosine –> Malonyl CoA (ketogenic)
Thymine –> methylmalonyl CoA or succinyl CoA (glucogenic)
Which aa can be used to form propionyl CoA which can then make succinyl CoA?
Threonine, methionine, isoleucine and valine
What is acyclovir?
Antiviral agent that undergoes phosphorylation by viral thymidine kinase conveerting it to acylco-dGMP
Acyclo-dGMP -> acyclo-dGTP which is incororpated into dividing viral cells and terminates replication
Used to tx sores related to chicken pox, shingles and HPV
How does tetracycline inhibit prokaryotic translation?
Binds to 30s su and blocks entry of aminoacyl-tRNA to ribosome impairing elongation
How does cyclohgeximide inhibit eukaryotic translation?
inhibits peptidyl transferase and impairs peptide bond formation
What is pyruvate carboxylase deficiency?
Mutations in pyruvate carboxylase gene causing more pyruvate to be converted to lactic acid (instead of OAA)
sx: appears after birth, seizures, muscle weakness, and uncontrolled muscle movements
Describe 2-oxoglutaric acid aciduria
sx: chronic metabolic acidosis, severe microcephaly, excretion of 2-oxoglutarate and fulmaric acid
Lethal w/in first 10 years of life
Describe the glycerophosphate shuttle
Present in skeletal muscle and the brain
Generates FADH2 in the IMM which then joins ETC at CoQ
Describe the secretory pathway of protein sorting
For proteins destined for the ER, lysosome, plasma membrane, or for secretion
Translation begins on free ribosome and ends on ribosomes sent to the ER
Each protein has an ER targeting signal
What is Hartnup disease?
Defective transport of non polar or neutral AA such as tryptophan
Manifests as failure to thrive, nystagmus, tremor, intermittent ataxia and photosensitivity
Describe pyruvate dehydrogenase deficiency (neonatal lactic acidosis)
Defect in PDC at E1 which effects males more bc gene is on X chromosome
High serum pyruvate and lactate
Tx: vitamin B1, lipoic acid and biotin supplements
Describe succinyl CoA synthetase (SCS) deficiency
Mutations in 2/3 of subunits for SCS in SUCLA2 and SUCLG1 genes
Deafness syndrome, dystonia, mild methylmalonic aciduria
How does chloramphenicol inhibit prokaryotic translation?
Inhibits peptidyl transverse and impairs peptide bond formation
What role does adenosine deaminase (ADA) play in purine catabolism?
Irreversible hydrolytic deamination of adenosine into inosine
Overproduction in RBC leads to hemolytic anemia
Underproduction associate with SCID
How does streptomycin inhibit prokaryotic translation?
binds to 30s and interferes with binding of fmet-tRNA impairing initiation
How do shiga toxin and ricin inhibit eukaryotic translation?
Bind to 60s and block entry of aminoacyl tRNA to ribosome
What is the signal sequence for nucleus proteins?
KKKRK
How do clindamycin and erythromycin inhibit prokaryotic translation?
Bind to 50s su blocking translocation of ribosome
What occurs when transfer of e- is inhibited?
Decrease in proton pumping and proton gradient
Inhibition of ATP synthase
Oxidation levels of purines
Adenosine > GMP and hypoxanthine > xanthine > uric acid (limits its solubility and plays a role in gout)
Describe the malate aspartate shuttle
Present in heart, liver and kidneys
Forms NADH into the mito matrix which then enters ETC at complex I
What do defects in the salvage pathway of purines lead to?
Excess guanine and hypoxanthine are shunted to form 6x normal levels of uric acid
Purine synthesis increases at levels 200x normal
What is SCID?
X linked disorder in adaptive immunity
Characterized by failure to thrive, thrush, chronic diarrhea, and recurrent viral, fungal and bacterial infections
What inhibits isocitrate dehydrogenase?
ATP and NADH
What is the signal sequence for secretory proteins?
tryptophan rich
What occurs in phosphatase deficiency?
PDC always phosphorylated/inactive form
Glucose made into lactate resulting in lactic acidosis
CNS mostly affected
Restrict alanine intake and recommended ketogenic diet
Which abx is the only elongation inhibitor?
puromycin (causes premature chain termination in both pro and eukaryotes)
What is methotrexate?
Cancer tx
Targets DHFR which converts dietary folate into tethrahydrofolate in the liver
Prevents oxidation of NADPH and inhibits DNA replication in rapidly dividing cells
Which aa can form fumarate?
Phe. tyrosine and aspartate
What is the signal sequence for peroxisome proteins?
C terminal SKL
Which abx inhibit eukaryotic translation?
Shiga toxin, ricin, diphtheria toxin and cycloheximide
Which abx are prokaryotic translation inhibitors?
Steptomycin, clindamycin, erythromycin, tetracycline and chloramphenicol
What are sulfa drugs?
Antibacterial agents that competitively inhibit the bacterial enzyme that incorporates PABA into folate
Selectively disrupt DNA replication in bacteria (since humans acquire folate as a vitamin the diet)
What is the benefit of depriving cells of GMP and dGTP?
Therapeutic intervention that targets IMP dehydrogenase
An immunosuppressant that disrupts DNA replication in B and T cells by depriving them of adequate GMP and dGTP
Prevents transplant rejection
Describe the cytoplasm pathway of protein sorting
For proteins destine for the cytosol, mitochondria, nucleus and peroxisome
Protein synthesis starts and ends on free ribosomes
What inhibits complex III?
Antimycin
What is Cockayne syndrome?
Autosomal recessive mutation in ERCC6 and 8 of TCR TCR repair
Neurologic delay, premature gaining (progeria), hearing loss and eye abnormalities
What is hereditary non-polyposis colorectal cancer?
Also known as Lynch syndrome
Mutation in MER complex gene
Accumulation of DNA damage leading to genomic instability and resulting in cancer
What is an example of a nonsense mutation?
Beta thalassemias
Lack of production of B-globin protein due to nonsense mutation
Homozygous mutation of splice sites + nonsense mutations that introduce premature stop signals at codons
What is an example of a frameshift mutation?
Cystic fibrosis
Most commonly caused by a delegation of 3 nts from the coding region —> loss of Phe in the CFTR protein
Protein doesnt fold properly, Cl channel doesnt function, result is thick and sticky mucus in lungs and pancreas
