7.05 Spring 2004 May 7, Recitation #11

Transcription

1 Recitation #11 ontact Information TA: Victor Sai Recitation: Friday, 3-4pm, ffice ours: Friday, 4-5pm, Unit 4 Schedule Recitation/Exam Date Topic Recitation #11 Friday, May 7 utting it all together Exam Review Friday, May 14, 1-3pm, Lectures Exam 4 Thursday, May 22, 1:30-3:00 Lectures Recitation verview Topic roblems 1. yridoxal- continued 1, Quiz 2. ne arbon Metabolism 2, [6] 3. Biosynthesis of urines and yrimidines 2, [6] 4. itrogen Metabolism, Urea ycle 3 5. Transformations of Aromatic Amino Acids 4 6. utting it all together 5 roblems 1. (1999 Exam 3 Question 2, 23 points) Based on principles presented in class, propose a method for the enzymatic conversion of the compound shown below to succinyl oa as one of the resulting products. In presenting your answer, use structural formulas and identify all reactants and products as well we coenzymes that may be needed. If you believe that pyridoxal- is involved, please present the mechanisms for any proposed reactions and include any proposed enzyme-bound intermediates Recitation 11 age 1 of 12

2 2 2 E-L 2 3 α 2-3 F 4 2 -F α : E-L non-enzymatic 3 AD AD SoA SoA 2 Thiamine- i FAD, Lipoate E-Biotin- 2 - AD i E-Biotin SoA 3 SoA Succinyl oa Vitamin B 12 oenzyme 2 - Recitation 11 age 2 of 12

3 2. (2001 Exam 3 Bonus Question, 10 points) Explain how serine could be used as a source of the carbons marked with an asterisk () in the nucleotides shown below. o need to use structural formulas in giving your answer. 3 dribose- IM Ribose- dtm F F 4 2 5,10-2 -F 4 AD Aldolase-like reaction E-L Glycine AD 5,10-Methenyl-F 4 Formate (10-formyl-F 4 ) Glycine 2 Glycine dum dtm IM 10-Formyl-F 5, F 4 F 2 R Formate (10-formyl-F 4 ) Recitation 11 age 3 of 12

4 3. (1994 Exam 3 Question 4, 20 points) Show how the amino group of isoleucine could be used to provide all of the atoms present in cytidine triphosphate T. Be sure to indicate how many mols of isoleucine are required to generate 1 mol of T. 3 Isoleucine 3 α ketoglutarate 3 Glutamate Glutamate 2 α ketoglutarate 2 AD 2 2 AD 2 Glutamate Glutamine 2 2 AD 2 i xaloacetate Aspartate Glutamate α ketoglutarate from Glutamine from Glutamine 2 2 from Aspartate T Recitation 11 age 4 of 12

5 4. (1995 Exam 3 Question 2, 15 points) The aromatic compounds shown below can be produced enzymatically from phenylalanine in individuals suffering from the metabolic disease, phenylketonuira. With the use of structural formulas show how these compounds could be produced from phenylalanine. o need to include mechanisms. But please indicate which coenzymes and cosubstrates may be needed. Assume the availability of any thioesterase that may be needed. a b α-ketoglutarate glutamate E-L 3 AD AD a. b AD SoA AD 2 2 SoA 2 thioesterase SoA Recitation 11 age 5 of 12

6 5. (1995 Exam 3 Question 4, 50 points) Show how glyceraldehyde-3- could be used to provide all of the carbons in the biosynthesis of the species of phosphatidyl choline shown below. lease indicate which, if any, coenzymes and cosubstrates may be needed for individual enzymatic steps. In presenting your answer, there is no need to use structural formulas, except for the final assembly of the compound from its component parts. 2 2 ( 2 ) ( 2 ) The four building blocks of phosphatidyl choline are 1) L-glycerol- 2) almitoyl oa 3) 4) S-Adenosyl methionine (SAM) Both L-glycerol- and can be obtained by modifying intermediates of glycolysis. almitoyl oa is obtained from fatty acid synthesis, which uses Acetyl oa. S-Adenosyl methionine can be obtained from one carbon metabolism. The pathway is shown on the next page. Recitation 11 age 6 of 12

7 AD AD Glyceraldehyde-3- AD i AD 1,3-di Glycerate AD AD AD 3--ydroxypyruvate 3--Glycerate Dihydroxyacetone- L-glycerol- L Glutamate α ketoglutarate i 2--Glycerate 2 -Enol-yruvate AD yruvate AD AD SoA 2 Acetyl oa fatty acid synthesis (shown on next page) Recitation 11 age 7 of 12

8 AD i E-Biotin- 2-3 SoA Acetyl oa 3 - E-Biotin SA SoA - SoA Malonyl oa - SA 3 SoA SA SoA 3 SA AD AD SA 2-3 SA 3 SA 3 2 SA AD palmitoyl oa SA SoA repeat 6 times to obtain palmitoyl A AD - SA 3 SA 3 SA 2 SA Recitation 11 age 8 of 12

9 Glycine 4 Folate L Folate 2 5,10-Methylene- 4 Folate AD Methionine 4 Folate omocysteine AD 5-Methyl- 4 Folate i i S-Adenosyl-methionine ow that we have the four building blocks, we can assemble the phosphatidyl choline as follows: 2 2 almitoyl oa R 2 R 2 L-Glycerol- 2 oa 2 hosphatidic Acid T i 2 R 2 R ytidine-di - Diacylglycerol (continued on next page) Recitation 11 age 9 of 12

10 2 2-3 M 2 R R hosphatidyl R hosphatidyl Ethanolamine R S-adenosyl-methionine (3-3 ) 3 S-adenosyl-homocysteine 2 R R 3 hosphatidyl holine Recitation 11 age 10 of 12

11 ractice roblem 6. (1999 Exam 3 Question 5, 11 points) During the metabolism of each of the following compounds labeled with 14 as shown with an asterisk, which carbon or carbons would be labeled in the indicated products in each case? Indicate with asterisks where the 14 would be found. Labeled ompound roduct a. 2 2 R' R b dribose- c Ribose d. 3 dribose- Recitation 11 age 11 of 12

12 a. b R R' dribose- c. d. 3 2 Ribose- dribose- Recitation 11 age 12 of 12

13 ne arbon Metabolism Victor Sai 7.05 Spring Folate R X AD AD E-L (aldolase-like reaction) 2 -Folate 3 Glycine Folate R X - 2 dtm dum AD AD Formyl- 4 -Folate 5,10-methenyl- 4 -Folate 5,10-methylene- 4 -Folate AD i AD - Formate AD 3 4 -Folate Vitamin B methyl- 4 -Folate S 3 S 3 3 Methionine omocysteine Adenosine i i S-Adenosyl-methionine (SAM) R X - R X 3 2 S-Adenosyl-homocysteine

14 Amino Acid Entry into TA ycle Glycolysis Gluconeogenesis β elimination E-L Victor Sai 7.05 Spring Enol-yruvate yruvate Transamination E-L Alanine Malate xaloacetate Acetyl oa Amino Acid Breakdown Amino Acid Breakdown Isoleucine Leucine itrate Amino Acid Breakdown Aceto acetate cis-aconitate - 2 Isoleucine 2 - Fumarate Succinate Amino Acid Breakdown Urea ycle Transamination E-L Aspartate Glu α KGA SoA Succinyl oa Amino Acid Breakdown 2 Valine α TA YLE α-ketoglutarate 2 Isocitrate xalosuccinate Amino Acid AD 3 Glutamate Transamination Glutamine Dehydrogenase AD 2 (only way to assimilate 3 into amino acids and Synthetase Keto Acid to move 3 to other compounds to form amino acids) AD i Glutamine 3 (Glutamine serves as a donor of 2 to other -containing compounds that are not amino acids) 3 Glutamate 3

15 Biosynthesis of yrimidine ucleotides Victor Sai 7.05 Spring 2004 Glu (Glutamine) Glu AD i 2 carbamoyl aspartate i carbamoyl aspartate 2 M 2-2 i R orotate 2 - AD AD F 2 F 2 2 dihydroorotate 2 - rotidylate Decarboxylase 2 RA Synthesis 2 2 AD UD AD 2 Glu 2 Glu 2 AD UM UT T 2 3 Thymidylate Synthase 5,10-2 -F 4 F 2 F dm i 2 dd AD B 12 coenzyme D 2 i dtm AD AD dum dt AD dtd AD dtt DA Synthesis

16 Mechanism for rotidylate Decarboxylase: S E S E S E R- - R- - 2 R- M UM Mechanism for Thymidylate Synthase: dr- - S dr- E 2 dum S E 5,10-2 -F 4 S dr- E 2 AD AD F 2 S dr- 3 E S E dr- 3 dtm

17 Biosynthesis of hospholipids & urines, ne arbon Metabolism AD AD AD Victor Sai 7.05 Spring 2004 AD Glyceraldehyde-3-1,3-di -Glycerate 3--Glycerate Glucose-6- Fructose-6- Fructose-1,6-di i AD AD 6--Gluconolactone 2 6--Gluconate AD AD 2 Ribulose-5- i 2 AD Dihydroxyacetone- AD L-Glycerol- 2 Acyl oa 2 oa hosphatidic Acid T i ytidine-di -Diacylglycerol 3--hydroxy-pyruvate Glutamate E-L α ketoglutarate i F 4 E-L AD AD AD 2--Glycerate 2 -Enol-yruvate yruvate AD SoA Isomerase M hosphatidyl F 4 2 Glycine AD Acetyl oa 2 Ribose-5- AM R 2 hosphatidyl Ethanolamine 3 S-adenosyl-methionine 3 S-adenosyl-homocysteine hosphatidyl holine F 2 dtm dum AD 5,10-2 -F 4 AD 5,10-Methenyl-F 4 AD AD 5-Methyl-F 4 Formate F 4 omocysteine Methionine 2 i i 2 Aspartate Formate (10-formyl-F 4 ) Glycine R Formate (10-formyl-F 4 ) Glu 2 2 Aspartate R 2 R 10-Formyl-F 4 RX - RX F 4 AD i S-adenosyl-methionine RX - RX 3 S-adenosyl-homocysteine 2 Adenosine Glu 2 R Glu 2 IM AM GM

18 Urea ycle Victor Sai 7.05 Spring AD carbamoyl Urea Arginine Fumarate 2 - : 2 3 rnithine rnithine AM i Arginino-succinate Aspartate : 2 itrulline AM A i A : Aspartate [Mechanism for itruilline Arginino-succinate]

19 General Enzymatic Transformations Monooxygenation Adds an group to benzene rings Victor Sai 7.05 Spring R R 4 -Biopterin 2 -Biopterin (or any other position) AD AD Example: Seen in henylalanine and Tyrosine Metabolism Biopterin 2 -Biopterin 3 henylalanine Tyrosine AD AD Methylation Adds a 3 group to nucleophilic groups S-Adenosyl methionine R X - R X 3 S-Adenosyl homocysteine Example: Seen in henylalanine and Tyrosine Metabolism S-Adenosyl methionine orepinephrine S-Adenosyl homocysteine 3 Epinephrine Example: S-Adenosyl methionine S-Adenosyl homocysteine 3 age 1 of 2

20 xidative Decarboxylation SoA replaces 2 SoA 2 R 2 - AD AD R SoA Thiamine- i FAD, Lipoate Thioesterification oxygen replaces SoA 2 SoA R SoA Thioesterase R - Addition of aldehyde groups to nucleophiles 10- F 4 F 4 R X - R X Example: Seen in Biosynthesis of urine ucleotides 2 2 F 2 Ribose Ribose Methylation of Alkenes Adds a 3 group to double bonds 5,10-methylene- 4 Folate 3 4 Folate 2 Folate dr dum AD AD dr dtm age 2 of 2

21 Biosynthesis of hospholipids glycolysis 2 AD DE V ATWAY 2 2 Acyl oa (2 Fatty Acids) 2 R 1 Victor Sai 7.05 Spring 2004 SALVAGE ATWAY 2 R 1 R 2 R 2 2 AD 2 2 oa 2 DA L-Glycerol- hosphatidic Acid 2 i 2 Diacylglycerol T i 2 ytidine-di - Diacylglycerol R R holine M AD R 2 2 R 1 3 -holine hosphatidyl T i 2 2 R hosphatidyl Ethanolamine R S-adenosyl-methionine (3-3 ) D-holine 3 S-adenosyl-homocysteine 2 R 1 R 2 3 hosphatidyl holine (Lecithin) M