BBMB 405 1st Edition Lecture 14 Outline of Last Lecture XIV Chapter 22 Fatty Acid Metabolism C Elongation and unsaturation of fatty acids are accomplished by accessory enzyme systems Continued D Handout 2 9 E Acetyl CoA Carboxylase plays a key role in controlling fatty acid metabolism XV Chapter 23 Protein Turnover and Amino Acid Catabolism A Handout 2 11 B Proteins are degraded to amino acids Outline of Current Lecture XV Chapter 23 Protein Turnover and Amino Acid Catabolism B Proteins are degraded to amino acids C Protein Turnover is tightly regulated D The First step in amino acid degradation is the removal of nitrogen E Ammonium ion is converted into urea in most terrestrial vertebrates Current Lecture XV Chapter 23 Protein Turnover and Amino Acid Catabolism Start on overhead Intracellular proteolysis 1 Use of stored amino acids These notes represent a detailed interpretation of the professor s lecture GradeBuddy is best used as a supplement to your own notes not as a substitute 2 Eliminate abnormal proteins 3 Permit regulation of enzymes Three methods of intracellular proteolysis 1 Lysosome system 2 Ubiquitin system 3 Ca activated proteases in muscle B Proteins are degraded to amino acids Continued 8 Cellular proteins are degraded at different rates some proteins are short lived and degrade quickly hemoglobin is limited only by life of red blood cell C Protein Turnover is tightly regulated 1 Ubiquitin tags proteins for destruction a Contributes to intracellular turnover b Ubiquitin binds to lysine 48 making an isopeptide bond through ATP hydrolysis then a few more are added making polyubiquitinated protein for degredation c d ATP driven ubiquitin conjugation e 2 Proteasome digests ubiquitin tagged proteins a Proteasome large protease complex that digests ubiquitinated proteins b Ends of barrel are control points target protein goes through center and is unfolded c d Overhead i Gardasil human papilloma virus Prevents cervical cancer ii iii Causes excessive activation of E3 for P53 tumor suppressor protein degradation If P53 is decreased then less chance of mutation and less chance of cancer Other E3 disease Early Onset Parkinson s disease ubiquitin system too slow not control cyclin which controls cell division so cells divide to quickly Angelman syndrome mental retardation Cystic Fibrosis Deficiency of chloride transport protein in lung pancreas and liver ATP dependent Mutation in phenylalanine ATP binding domain Mutant protein not folded properly and degraded by ubiquitin system e Handout 2 11 no lysosome in brain protein degraded by endocytosis then creating a phagosome origin bacteria virus or endosome origin protein then fusion with lysosome where protein is degraded to amino acids by proteases lysosome hydrolyze protein in low pH usually pH 5 lysosome activity increases in muscle atrophy f Rumen Dietary protein is substrate for microbes which makes amino acids which are then degraded further to make ATP then animal uses ammonia to make amino acids and in turn protein rumen live on microbial proteins 3 Protein degradation can be used to regulate biological function D The First step in amino acid degradation is the removal of nitrogen 1 Alpha amino groups are converted into ammonium ions by oxidative demination of glutamate a Aminotransferases aka transaminases catalyze transfer of alpha amino group from alpha amino acid to alpha ketoacid reactions are reversible b c Glutamate dehydrogenase d Show that alpha ketoglutarate and glutamate work together e f Know amino acid structures lose N group to make ammonia and what else alanine makes pyruvate 2 Mechanism pyridoxal phosphate forms Schiff base intermediates in aminotranserases 3 Asparate aminotransferase in archetypal pyridoxal dependent transaminase 4 Pyridoxal phosphate enzymes catalyze a wide array of reactions a Coenzyme Vitamin B12 b Focus on Transamination decarboxylation deamination 5 Serine and threonine can be directly deaminated a Serine pyruvate NH4 b Threonine alpha ketobutyrate NH4 6 Peripheral tissues transport nitrogen to the liver Alanine Cori Muscle 2 Alanine 2 Pyruvate 2 Lactate Glycolysis 2ATP Glucose Blood 2 Alanine Liver 2 Glucose 2 Lactate Glucose Gluconeogenesis 2ATP 2 Alanine 2Pyruvate 2 Lactate 2 Alanine NH2 4ATP Urea Deamination Degraded transferred to pyruvate and make glucose E Ammonium ion is converted into urea in most terrestrial vertebrates 1 Overview went through in class will go through in more detail next lecture 2 3 Make 35g day of urea
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