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Chapter 18

Chapter 18. Amino Acid Oxidation and the Production of Urea. Amino Acid Oxidation, Production of Urea. Key topics : To Know. How proteins are digested in animals How amino acids are degraded in animals as a source of energy How urea is made and excreted

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Chapter 18

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  1. Chapter 18 Amino Acid Oxidation and the Production of Urea

  2. Amino Acid Oxidation, Production of Urea Key topics: To Know • How proteins are digested in animals • How amino acids are degraded in animals as a source of energy • How urea is made and excreted • Some genetic defects in amino acid recycling

  3. The use of amino acids as fuel varies greatly by organism • About 90% of energy needs of carnivores can be met by amino acids immediately after a meal • Microorganisms scavenge amino acids from their environment for fuel when needed • Only a small fraction of energy needs of herbivores are met by amino acids • Plants do not use amino acids as a fuel source, but can degrade amino acids to form other metabolites

  4. Metabolic Circumstances of Amino Acid Oxidation • Leftover amino acids from normal protein turnover • Dietary amino acids that exceed body’s protein synthesis needs • Proteins in the body can be broken down to supply amino acids for energy when carbohydrates and fats are scarce (starvation, diabetes mellitus)

  5. Overview

  6. Proteosome Function Core Proteasome Ubiquitin Binding Sites top and bottom Nature 445:618 Feb 8, 2007

  7. Ubiquitin Targeting a Cytoplasmic Protein 5th Edition: See pages 1107-1109, Fig 27-47, -48 6th Edition: See pages 1147-1149, Fig 27-47, -48. Protein Amino Terminal-aa Determines Protein’s Half-life stabilizing M, G, A, S, T, V >20 hrs destabilizing I, N, Y, D, P, L, F, D, K, R 30 – 2 min

  8. Nitrogen Delivered to Liver Cells

  9. Nitrogen Excretion Forms

  10. Transaminases EOC Problem 1 a Transamination Problem.

  11. PLP – Transaminase Cofactor

  12. Transaminases Used in Diagnosis of Tissue Damage Tissue damage  leaks enzymes into blood (S)GPT: glutamate-pyruvate transaminase (S)GOT: glutamate-oxaloacetate transaminase -- indicate probable liver damage (toxins, infections) (S)CK: creatine kinase -- heart damage  heart attack, infection S for “serum” EOC Problem 2: Measuring transaminases in blood – coupled reactions! (to things you already know)

  13. Glutamate Dehydrogenase

  14. Glutamine Synthetase This is just one reaction: Glutamine Synthetase

  15. Glucose-Alanine Cycle is in Muscle Only EOC Problem 3: Alanine and Glutamine in Blood.

  16. Urea Cycle Overview Amino acids come from recycling (glutamine), muscle glycolysis (alanine), and diet.

  17. Begin in the Mitochondrion

  18. Mechanims of the Two Nitrogen Entry Points in Urea Cycle

  19. Relationship to Citric Acid Cycle EOC Problem 4: Alanine and Lactate have identical oxid-state, why do cells get less energy from alanine? EOC Problem 8: Asp Transaminase activitiy.

  20. Urea Cycle Controlled Acetyl-Glutamate Acetyl-Glu is in the Arg synthetic pathway in bacteria and plants, in animals it is only regulatory

  21. Benzoate and Phenylbutyrate Given to Lower Blood Ammonium Treatment for genetic defects in Urea Cycle Excreted in Urine

  22. Summary of Amino Acid Catabolism

  23. 1 Carbon Transfer Cofactors

  24. Pyruvate Family

  25. Glycine Degradation in Kidney • D-amino acid oxidase breaks down D-aa’s from bacterial peptidoglycan. • Oxalate-Ca++ are major substance in kidney stones.

  26. Acetyl-SCoA Family

  27. Other Uses of W’s Indole Ring

  28. Phenylalanine Degradation

  29. PKU = Phenylketouria EOC Problem 11: Analysis of blood and PKU

  30. α-KetoGlutarate Family

  31. Succinyl-SCoA Family

  32. Oxaloacetate Family

  33. Amino Acid Carbon Use

  34. Things to Know and Do Before Class • Amino acids from protein are an important energy source in carnivorous animals and during starvation. 2. The first step of AA catabolism is transfer of the NH3 via PLP-dependent aminotransferase usually to - ketoglutarate to yield L-glutamate. 3. In most mammals, toxic ammonia is quickly converted to carbamoyl phosphate and passed into the urea cycle 4. Amino acids are degraded to pyruvate, acetyl-CoA, α- ketoglutarate, succinyl-CoA, and/or oxaloacetate 5. Amino acids yielding acetyl-CoA are ketogenic. 6. Amino acids yielding other end products are glucogenic. • Genetic defects in amino degradation pathways result in a number of human diseases: our example is PKU. • EOC Problems 1-5, 8, 11.

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