BBMB 405 1nd EditionExam # 2 Study Guide Lectures: 12 - 22Chapter 23: Protein Turnover and Amino Acid Catabolism Lectures 12-161. Proteins are denatured by acid in stomach. This denaturation makes them better substrates for proteolysis. Explain why this is the case.A: Proteins exist in three dimensional tertiary structures which usually prevent access of proteases to all peptide bonds of structure; when denatured tertiary structure of protein is broken and in denatured state all peptide bonds can be accessed. Proteases can better degrade proteins to amino acids and oligopeptides.2. What are steps required to attach ubiquitin to target protein?3. Match description on right with term on left.a. Pepsin: 7. Stomach proteolytic enzymeb. N-terminal rule: 4. Determine half-life of protein.c. Ubiquitin: 2. Marks protein for destructiond. PEST sequences: 10. Pro-Glu-Ser-Thre. Threonine nucleophiles: 5. 20S coref. ATP-dependent protein unfolding: 3. 19S regulatory subunitg. Proteasome: 9. Protein degrading machineh. Ubiquitin-activatin enzyme: 1. An adenylate intermidatei. Ubiquitin-conjugating enzyme: 6. Substrate for ubiquitin-ligasej. Ubiquitin-ligases: 8. Recognize protein to be degraded4. Protein hydrolysis is exergonic process, yet 26S proteasome is dependent on ATP hydrolysis for activity.a. Although exact function of ATPase activity is not known, suggest some likely functions.A: Proteasomes cannot directly interact with all peptide bonds of protein, because protein is organized into tertiary structure which is caused by energetically favorable interactionsbetween residues of protein. To access peptide bonds, interactions must be broken. So the disruption of the interaction that make tertiary structures could require ATP.b. Small peptides can be hydrolyzed without expenditure of ATP. How does this information concur with your answer to part a?A: Since small peptides are too short to have tertiary structures, proteasomes can access peptide bonds without needing to use ATP. Information agrees with part a answer.5. Name the alpha ketoacid that is formed by transamination of each of following amino acids:a. Alanine  Pyruvateb. Aspartate  Oxaloacetatec. Glutamate  Alpha ketoglutarated. Leucine  alpha ketoisocaproatee. Phenylalanine  phenylpyruvatef. Tyrosine  hydroxyphenylpyruvate18. Four high-transfer-potential phosphoryl groups are consumed in the synthesis of urea according to the stoichiometry given onpage 687. In this reaction, aspartate is converted into fumarate. Suppose that fumarate is converted into oxaloacetate. What is the resulting stoichiometry of urea synthesis? How many high-transfer-potential phosphoryl groups are spent?A: CO2 + NH4+ + 3ATP + aspartate + 3H2O + NAD+  Urea + 2ADP + 2Pi + AMP + PPi + oxaloacetate + NADH+ H+Although the reaction still consumes four high energy phosphoryl groups, the conversion of fumarate to oxaloacetate yields NADP which is the equivalent of 2.5 ATP. The net expense of the reaction is 1.5 ATP units.21. Glutamate is important neurotransmitter whose levels must be carefully regulated in brain. Explain how high concentration of ammonia might disrupt this regulation. How might high concentration of ammonia alter citric acid cycle?A: Amino acid degradation and nitrogen recycling and removal are essential for preventing the formationof toxic metabolites in the body. In a few steps of the removing nitrogen process the transfer of amino groups to other metabolic intermediates is involved. One essential step in amino acid metabolism and nitrogen recycling is the formation of glutamate via transfer of an amino group. When excess ammonia is present in the body, a similar reaction results in increased accumulation of glutamate. Levels of the neurotransmitter glutamate are carefully regulated. The excess ammonia will disrupt glutamate levels and cause excessive stimulation by the neurotransmitter and damage neurons. The citric acid cycle is affected because the excess ammonia will funnel out alpha ketoglutarate from the cycle to synthesis glutamate. The lack of alpha ketoglutarate will slow down the citric acid cycle and reduce respiratory ability of cell.22. Urine of an infant gives positive reaction with 2,4-dinitrophenylhydrazine. Mass spectrometry shows abnormally high blood levels of pyruvate, alpha-ketoglutarate, and alpha ketoacids of valin, isoleucine, and leucine. Identify likely molecular defect and propose definitive test of your diagnosis.A: Mass spectroscopy shows high levels of pyruvate, alpha ketoglutarate, and alpha ketoacids of valine, isoleucine, and leucine. This indicates that the enzyme responsible for degradation of keto acids, pyruvate, and alpha ketoglutarate is missing or deficient. Enzymes could be pyruvate dehydrogenase, alpha ketoglutarate dehydrogenase, and alpha ketoacid dehydrogenase. To test theses enzymes, they can be purified and assayed for their capability to catalyze regeneration of lipoamide.23. How would you treat infant who is deficient in argininosuccinate synthetase? Which molecules wouldcarry nitrogen out of body?A: Argininosuccinate synthetase is used to synthesize argininosuccinate from citrulline and aspartate in urea cycle. Infant who is deficient cannont synthesize argininosuccinate and cannot carry out urea cycle.Benzoate, phenylacetate, and arginine would given.24. As we will see later, liver damage often results in ammonia poisoning. Explain why this is the case.A: Liver has most ammonium in body and is removed by synthesis of urea. If liver is damaged by cirrhosis (can no longer remove ammonium), there will be elevated levels of ammonia in blood.26. Why should phenylketonurics avoid using aspartame, an artificial sweetner? (Hint: Aspartame is L-aspartyl-L-phenylalanine methyl ester)A: Phenylketonuria is caused by accumulation of phenylalanine in body fluids resulting in the inability of phenylalanine being converted to tyrosine which is an essential step for its degradation. This is caused bydeficiency of phenylalanine hydroxylase or the lack of its coenzyme tetrahydrobiopterin which renders the enzyme inactive. Apsartame is L-aspartyl-L-phenylalanine methyl ester. One of the breakdown products of aspartamine is amino acid phenylalanine. The ingestion of aspartame will result in further increase and accumulation of phenylalanine and would worsen condition of phenylketonuric patients.27. N-Acetylglutamate is required as cofactor in synthesis of carbamoyl