The hypoxanthine analogue Allopurinol, which effectively treats gout , has no effect on the severe neurological symptoms of Lesch- Nyhan patients because it does not A. decrease de novo pyrimidine synthesis B. decrease de novo purine synthesis C. decrease urate synthesis D. increase PRPP levels (Phosphoribosyl pyrophosphate
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- In 2-page worth of words (around 500), discuss CYCLAMATE's regulation, allowable levels, and what group of people are at high risk for the side effects of CYCLAMATE in the body.The epinephrine-mediated “amplificationcascade” of Figure 24.14 has six steps, all of which are catalyticwith one exception. This cascade leads to the activation of glycogenphosphorylase. This enzyme acts in turn on glycogen to yieldglucose-1-phosphate (G-1-P).(a) Which step is not catalytic?(b) If each catalytic step had a turnover (molecules of substrateacted on per molecule of enzyme) of 10, how many moleculesof G-1-P would result from one molecule of epinephrine?(c) What is the biochemical advantage of such a cascade?(d) How is the amplification cascade of this questionreversed?A mutant form of polypeptide hormone angiotensin II has the amino acidcomposition (Asp, Arg, Ile, Met, Phe, Pro, Tyr, Val)The following observations are made:• Trypsin yields a dipeptide containing Asp and Arg and a hexapeptide withall the rest.• Cyanogen bromide cleavage yields a dipeptide containing Phe and Proand a hexapeptide containing all the others.• Chymotrypsin cleaves the hormone into two tetrapeptides, of composition (Asp, Arg, Tyr, Val) and (Ile, Met, Phe, Pro)• The dipeptide of composition (Pro, Phe) cannot be cleaved by either chymotrypsin or carboxypeptidase.What is the sequence of angiotensin II?
- Provide a diagram of the EPH RECEPTOR B2 (EPHB2) structure. Give annotations of binding sites and enzyme active sites.A female neonate did well until approximately 24 hours of age when she became lethargic. A sepsis workup proved negative. At 56 hours, she started showing focal seizure activity. The plasma ammonia level was found to be 1,100 μmol/L (normal 5–35 μmol/L). Quantitative plasma amino acid levels revealed a marked elevation of argininosuccinate.19.3 Which one of the following enzymic activities is most likely to be deficient in this patient? EXPLAIN your answerA. Arginase.B. Argininosuccinate lyase.C. Argininosuccinate synthase.D. Carbamoyl phosphate synthetase I.E. Ornithine transcarbamoylase.Azathioprine is an immunosuppressant drug used in kidney transplants. In vivo, azathioprine is metabolized to the hypoxanthine analog 6- mercaptopurine, which is then converted into 6-mercaptopurine ribose monophosphate, the active form of the drug. 6- Mercaptopurine ribose monophosphate also inhibits de novo purine synthesis, reducing uric acid levels in the blood and urine. However, when administered to Lesch – Nyhan patients, there was no effect on uric acid levels. Explain why this is the case.
- At body temperature, L-aspartate in proteins race-mizes to D-aspartate at an appreciable rate. Most pro-teins in the body have a very low level of D-aspartate, if itcan be detected at all. Elastin, however, has a fairly highlevel of D-aspartate. Moreover, the amount of D-aspartateincreases in direct proportion to the age of the person fromwhom the sample was taken. Why do you suppose thatmost proteins have little if any D-aspartate, while elastinhas levels of D-aspartate that increase steadily with age?CTP inhibits ATCase; however, the inhibition is not complete. Can you suggest another molecule that might enhance the inhibition of ATCase?When the pathogen Salmonella typhimurium infects mammalian cells, the host cell protease caspase-1 is enabled to cleave and thereby activate signaling proteins that instigate the immune response. The targets of caspase-1 also include aldolase and enolase. What eff ect would this have on the infected cell and why might this be advantageous to the organism?
- Other symptoms of congenital adrenal hyperplasia include excess facial hair in women and early puberty in men (~ 2 years old!) from the effects of excess testosterone. Using the law of mass action, explain why this mutation results in excess testosterone production. Use the name of the substrate and the product of the reaction.The drug troglitazone was used to treat diabetes but was withdrawn from the market when patientswho took the drug suffered from severe side effects. The data below show the activity of an enzymein the steroid biosynthetic pathway in the presence and absence of 10 µM troglitazone.[S] (µM) v0 (pmol min-1)Create a plot of 1/v0 vs. 1/[S]. Calculate KM and vmax in presence and absence of inhibitor. Whattype of inhibitor is troglitazone? Clearly support your answer.Many patients with glucose 6- phosphatase deficiency have high serum levels of urate. Hyperuricemia can be induced in normal people by the ingestion of alcohol or by strenuous exercise. Propose a common mechanism that accounts for these findings.