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BCH 304 STUDY QUESTIONS & ANSWERS Biochemist

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BCH 304 STUDY QUESTIONS & ANSWERS Biochemist Oh!Best Q1- What is the difference between De-novo synthesis of nucleotide and nucleotide synthesis by the salvage pathways? Answer: In De-novo synthesis, the nucleotides are synthesized from simpler precursor compounds, in essence from scratch. In salvage pathways, preformed bases are recovered and attached to ribose. Q2- Identify the sources of the atoms of purines and pyrimidines ring during their De-novo synthesis. Answer: In purines: i. Glycine provides C4, C5 and N7 5 10 ii. N , N -Formyl tetrahydrofolate (THF) provides C2 and C8 iii. Glutamine provide N3 and N9 iv. CO2 provide C6 v. Aspartate provides N1 In pyrimidines: Glutamine Aspartic acid CO2 i. Glutamine provides N3 ii. Aspartic acid provides C4, C5, C6 and N1 iii. Carbon dioxide (CO2) provides C2 Q3- Create a match (a) Excessive urate___ Spina bifida (b) Lack of adenosine deaminase___ Precursor to both ATP and GTP (c) Lack of HGPRT___ Purine (d) Carbamoyl phosphate___ Deoxynucleotide synthesis (e) Inosinate___ UTP (f) Ribonucleotide reductase___ Lesch-Nyhan disease (g) Lack of folic acid___ Immunodeficiency (h) Glutamine phosphoribosyl transferase___ Pyrimidine (i) Single ring___ Gout (j) Bicyclic ring___ First step in pyrimidine synthesis (k) Precursor to CTP___ Committed step in purine synthesis Answer: (a) Excessive urate___ Gout (b) Lack of adenosine deaminase___ Immunodeficiency (c) Lack of HGPRT___ Lesch-Nyhan disease BCH 304 STUDY QUESTIONS & ANSWERS Biochemist Oh!Best (d) Carbamoyl phosphate___ First step in pyrimidine synthesis (e) Inosinate___ Precursor to both ATP and GTP (f) Ribonucleotide reductase___ Deoxynucleotide (g) Lack of folic acid___ Spina bifida (h) Glutamine phosphoribosyl transferase___ Committed step in purine synthesis (i) Single ring___ Pyrimidine (j) Bicyclic ring___ Purine (k) Precursor to CTP___ UTP Q4- Azaserine (an analog of glutamine) inhibits the enzyme amido transferase. Identify the intermediate of purine biosynthesis that would accumulate in cells treated with Azaserine. Answer: The intermediate that would be accumulated in the cells are PRPP and formyl glycinamide ribonucleotide (FGAR). Q5- Discuss the inhibitory action of sulfanilamide and related sulfa drugs in bacteria growth in relation to nucleotide biosynthesis. Answer: There is a deficiency of N10-formyltetrahydrofolate. Sulfanilamide inhibits the synthesis of folate by acting as an analog of p-aminobenzoate, one of the precursors of folate. Q6- What are the functions of Carbamoyl phosphate synthetase (CPS)- I & II Answer: CPS-I is an enzyme located in the mitochondria involved in the production of urea. CPS-I transfers an ammonia molecule from glutamine or glutamate to a molecule of bicarbonate that has been phosphorylated by a molecule of ATP. It can only be activated by N-acetylglutamate. CPS-II is an enzyme that catalyzes the reactions that produce carbamoyl phosphate in the cytosol (as opposed to type I, which functions in the mitochondria) and it involve in pyrimidine synthesis. It is activated by ATP and PRPP and it is inhibited by UMP. Q7- Give the reaction of purine biosynthesis via the salvage pathway Adenine, hypoxanthine, guanine produced during the breakdown of high energy compounds like RNA and DNA, are salvaged to produce AMP, IMP, GMP. Adenine phosphoribosyl transferase catalyzes the formation of AMP from adenine. Hypoxanthine-guanine phosphoribosyl transferase (HGPRT) catalyzes the formation of IMP and GMP from hypoxanthine and guanine respectively. BCH 304 STUDY QUESTIONS & ANSWERS Biochemist Oh!Best Phosphoribosyl pyrophosphate (PRPP) is the donor of ribose 5-phosphate in the salvage pathway. Q8- Briefly explain the biochemistry of Lesch-Nyhan’s syndrome Lesch Nyhan syndrome is an inherited X-linked recessive disorder that affects only males mostly. It is caused by a complete deficiency of HGPRTase [an enzyme involves in purine salvage pathway] and purine (hypoxanthine and guanine) will accumulate. The HGPRTase enzyme catalyzes the following two interconversions: hypoxanthine + PRPP ↔ IMP + PPi guanine + PRPP ↔ GMP + PPi The symptoms are: urinary tract stones, mental retardation or neurological symptoms, self-mutilation (biting of fingers), excessive uric acid production. It can be treated as follows; i. Use of allopurinol: - It will only reduce uric acid formation, but does not alleviate the neurologic symptoms ii. Alkalanization of urine should be avoided. iii. High fluid intake. Q9- Name one nucleotide that acts in each of the following: (a) Second messenger (b) Phosphoryl-group transfer (c) Activation of carbohydrates (d) Activation of acetyl groups (e) Transfer of electrons (f) DNA sequencing (g) Chemotherapy (h) Allosteric effector Answer: (a) cAMP (b) ATP (c) UDP-glucose (d) acetyl CoA (e) NAD+, FAD (f) dideoxynucleotides (g) fluorouracil; (h) CTP inhibits ATCase. BCH 304 STUDY QUESTIONS & ANSWERS Biochemist Oh!Best Q10a- Discuss the De-novo synthesis of UMP UMP which is pyrimidine nucleotide is formed via the De-novo biosynthesis DHO dehydrogenase + CO2 Carbamoyl phosphate Synthetase II [CPS-II] Orotate Orotate Phosphoribosyl transferase Carbamoyl phosphate [CAP] Aspartate transcarbamylase [ATCase] Orotidine-5-monophosphate [OMP] Carbamoyl aspartate [CAA] OMP decarboxylase Dihydroorotase Dihydroorotate [DHO] Uridine-5-monophosphate [UMP] Q10b- How is this pathway regulated? The first two enzymes; carbamoyl phosphate synthetase II [CPS-II] and aspartate transcarbamoylase [ATCase] are allosteric enzymes and are regulated allosterically. Q11- If man did not lose his urate oxidase, gout would have been an unknown disease. Discuss? Gout is a clinical disorder caused by deposition of urate crystals in a joint leading to acute inflammatory response with acute pain. Most cases of gout present with the sudden onset of severe acute arthritis in a peripheral joint in the leg. Urate oxidase is a peroxisomal liver enzyme that catalyzes the enzymatic oxidation of uric acid into the more water-soluble allantoin. Urate oxidase is an endogenous enzyme found in most mammals but not in humans, which was actually caused by two (2) independent nonsense or frameshift mutations. BCH 304 STUDY QUESTIONS & ANSWERS Biochemist Oh!Best Allopurinol blocks the conversion of xanthine to uric acid, while the urate oxidase catalyzes the oxidation of uric acid to allantoin, a highly water-soluble metabolite readily excreted by the kidney. Although urate oxidase is not found in humans, but urate oxidase is used in humans for the control of increased serum uric acid in patients with acute tumour lysis syndrome after receiving chemotherapy. Q12a-Highlight the reactions of purine nucleotide cycle The purine nucleotide cycle is a metabolic pathway in which ammonia and fumarate are generated from aspartate and inosine monophosphate (IMP) in order to regulate the levels of adenine nucleotides. The cycle is composed of three enzyme-catalyzed reactions. The first stage is the deamination of the purine nucleotide Adenosine monophosphate (AMP) to form inosine monophosphate (IMP), catalyzed by the enzyme AMP deaminase: + AMP + H2O → IMP + NH4 The second stage is the formation of adenylosuccinate from IMP and the amino acid aspartate, which is coupled to the energetically favourable hydrolysis of GTP, and catalysed by the enzyme adenylosuccinate synthetase: Aspartate + IMP + GTP → Adenylosuccinate + GDP + Pi Finally, Adenylosuccinate is cleaved by the enzyme adenylosuccinate lyase to release fumarate and regenerate the starting material of AMP: Adenylosuccinate → AMP + Fumarate Q12b- How is the above pathway relevant to muscle contraction? + This cycle has the net effect of converting aspartate to fumarate plus NH4 . It plays an important role in energy metabolism in skeletal muscle, where the fumarate that it generates replenishes the levels of citric acid cycle intermediates lost in amphibolic side reactions. Skeletal muscle lacks the usual complement of anaplerotic enzymes and relies on enhanced levels of AMP deaminase, adenylosuccinate synthetase, and adenylosuccinate lyase to compensate. ATP → ADP + Pi (utilization of ATP for Muscle contraction) Purine nucleotide cycle occurs during strenuous exercise, fasting or starvation when ATP reservoirs run low. Enjoy a Stressless Exam… BCH 304 STUDY QUESTIONS & ANSWERS Biochemist Oh!Best .
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