Biochemistry Review I: Molecular & Cellular Flashcards
Why does DNA have a negative charge?
What two amino acids are histones rich in, and why?
DNA carries phosphate groups on its sugar backbone. Histones are (+) charge heavy, rich in lysine and arginine, they bind up the negatively charged DNA.
There are 3 amino acids which are necessary for de novo purine synthesis. What are they?
Which nucleotides are purines?
The purines are PURe As Gold: A, G. You need: Glycine Aspartate Glutamine (GAG) to make purines.
What molecule is the source of phosphate for both purine and pyrimidine de novo synthesis?
Where do you get this molecule?
PRPP
PRPP is made from ribose-5-P, which is produced in the HMP shunt / pentose phosphate pathway.
The pentose phosphate pathway has an oxidative and a non-oxidative part.
Which part contains the rate-limiting enzyme, and what is this enzyme?
What are the two important products of this pathway, and what are they used for?
Why is the above-mentioned enzyme so vital to RBCs?
The first portion is oxidative, rate-limiting, and is irreversible.
It uses the enzyme G-6-P dehydrogenase to make NADPH (used in reduction reactions, synthesis of cholesterol, steroids, CYP450…) and Ribulose-5-P (used to make ribose-5-P, which will be used to make brand new nucleotides).
RBCs rely on this pathway and G6PD to make NADPH, which they use to reduce glutathione and limit oxidative damage.
Orotic aciduria is a defect in de novo purine synthesis. You cannot make CTP / dTMP.
Which enzyme is defective in this disorder?
How is it inherited?
What are the clinical manifestations?
UMP synthase takes orotic acid down the path to making pyrimidines de novo.
This is AR, as are most of the messed up metabolic things.
Clinical: Orotic acid accumulates in the urine. Urea cycle is fine, so ammonia levels are normal. Usually shows up in kids as FTT, megaloblastic anemia that does not get better with B12/folate administration.
Treatment is to bypass orotic acid -> UMP by giving uridine directly.
The most common cause of SCID is actually a purine salvage problem. An excess of ATP/dATP feeds back negatively to pyrimidine synthesis and shuts it down. What is this disorder called, and what effect does this have on the immune system? What are the three common clinical manifestations of SCID in early life?
DNA synthesis is hindered in adenosine deaminase deficiency. You cannot recycle adenosine, and impaired salvage shuts down pyrimidine synthesis.
No DNA = no new immune cells.
SCID shows up as FTT, severe recurrent infections, and constant diarrhea.
Lesch-Nyhan is X-linked recessive, you may see a boy child with aggression, mental retardation, and self-mutilating behaviors.
What is the enzyme deficiency in Lesch-Nyhan syndrome?
If you don’t have this enzyme, what will you find in the urine? How do you treat this excess?
HGPRT. (Remember, He’s got Purine Recovery Trouble.)
No HGPRT = hypoxanthine accumulation. Hypoxanthine would normally be sent back up to salvage path to make purines, but instead it gets made into xanthine and then uric acid.
Lesch-Nyhan -> Hyperuricemia. This causes gout. Treat with allopurinol, which blocks conversion of xanthine to uric acid by the enzyme xanthine oxidase.
Questions about RNA polymerases:
Which eukaryotic RNA pol. does amanitin poison? What does this polymerase make, and where does it make it?
How many RNA polymerases do prokaryotes have?
What is the drug that works on the prokaryotic RNA polymerase?
Amanitin inhibits RNA pol. II. This polymerase makes mRNA in the nucleoplasm.
Prokaryotes have only one RNA polymerase, and rifampin is the drug that poisons it.
Recall your mnemonic for antibiotics acting to inhibit protein synthesis. Where does each work?
He buys AT 30
CCELS at 50:
Aminoglycosides (& streptomycin) cause misreading at 30S, block initiation.
Tetracyclines prevent tRNA from binding at 30S.
Chloramphenicol binds 50S and blocks peptidyltransferase.
Clindamycin binds the 23S inside the 50S.
Erythromycin (macrolides) prevent release of tRNA from the 50S (a “macro” complex is formed)
Linezolid acts like clinda
Streptogramins act like chloramphenicol
I cell disease comes about as a result of a problem with the golgi apparatus’ ability to tag proteins so that they are addressed to lysosomes instead of to the outside world. What is the failed step in this process?
What are the clinical manifestations of this disorder?
I cell disease is an inherited lysosomal storage disorder.
Mannose-6-phosphate is added to lysosome bound proteins by the enzyme phosphotransferase. If this does not happen, proteins that should be bound for destruction are instead excreted into the extracellular environment.
Clinical manifesatations: Fatal in childhood. Coarse facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes.
This organelle is involved in the catabolism of very long chain fatty acids and amino acids:
Peroxisome.
Chediak-Higashi syndrome is actually caused by a problem with lysosomal traffic regulation. You remember this as an immune deficiency associated with albinism and peripheral neuropathy.
What is the gene involved?
Why is there immune deficiency in this disorder?
What is the characteristic cellular finding in Chediak-Higashi syndrome?
The gene is LYST = lysosomal traffic regulator gene.
Microtubules sort proteins into endosomes and send them into lysosomes for destruction. Phagocytes have lysosomes, too… they use them to kill things, especially Staph. and Strep.
You see huge cytoplasmic granules in neutrophils.
You know Alport Syndrome as a defect in type IV collagen, and you remember “IV on the FLOOR” – type IV collagen is a component of the basement membrane. Which three organs are most heavily hit by type IV collagen abnormalities in Alport? How is this disorder inherited? What are the clinical manifestations?
Alport is X-linked recessive.
Type IV is found in the BM of the:
Kidney -> hereditary nephritis
Eyes -> lenticonus (= thinning of capsule around lens), ocular problems
Ears -> deafness
Remember the mnemonic? “Can’t pee, can’t see, can’t hear me.”
Marfanoid habitus is an example of locus heterogeneity, where the idea is that you can end up with the same phenotype by way of changes at very different loci. Three disorders that can cause Marfanoid habitus?
Marfan syndrome
Homocystinuria
MEN 2B
