1. The Big Picture of Protein Metabolism Gladys Kaba

2. INTRODUCTION- General Structure of Amino acid (AA) 2 Carboxylic acid Acetic acid Amino acid (AA)

3. R-Group or Side chains 1) AA with Nonpolar R group (hydrophobic)- 2)AA with Polar R group (hydrophilic) i) AA with Polar uncharged R group– ii)AA with Basic R group (charged) iii)AA with Acidic R group (charged) 3 The 21 Different Amino Acids(AA) Can Be classified into -----

4. 4 Abbreviations and symbols of Amino acids

5. 5  Dipeptide, tetrapeptides, pentapeptides, etc  few amino acids are joined ------ oligopeptide.  many amino acids are joined----- polypeptide (protein usually >50 amino acids) PEPTIDE AND PROTEIN

6. Levels of Protein Structure 6

7. 1.Primary structure --- refers to the sequence of amino acids in a protein. 2. The secondary structure ----- refers to the first level of folding. Common secondary structures-- alpha helix, beta- pleated sheet, and triple helix. hydrogen bonds between backbone 7

8. Alpha helix 8

9. 9 1. Hydrophobic interactions 2. Hydrophilic interactions 3. Salt bridges 4. Hydrogen bonds 5. Disulfide bonds 3. Tertiary structure: additional folding and additional bond formation which may involve--

10. 10 4. Quaternary structure: protein consisting of two or more peptide subunits  Quaternary structure is held together by the same forces that hold tertiary forces together.  Example: haemoglobin -- two alpha chains, two beta chains-- Four polypeptide chains come together.

11. 11

12. 12 Denaturation Protein Hydrolysis / Denaturation A protein or peptide can be hydrolyzed into individual amino acids.

13. 13 1.) What structural level of a protein is affected by denaturation? How is this different from the structural level of a protein affected by hydrolysis? Problem 8

14. 14 AMINO ACID, PEPTIDE AND PROTEIN METABOLISM 1) Catabolism (protein, amino acid degradation)-  Excess AA excreted(Carbon skeleton, amino group) (2)Regulation of amino acid catabolism 3) Amino acid synthesis (Anabolism).  essential and non essential amino acid. 4) Errors of protein metabolism and clinical significance

15.  Excess amino acid (protein) can not be stored and need to be excreted.  (from diet and cellular proteins) Amino Acid, Peptide And Protein (A) Catabolism Introduction

16. ( B) degradation of cellular proteins which occur in all cells. 1) ATP-independent pathway - lysosomes, 2) ATP-dependent pathway - degradation in proteasomes (a polymer of ubiquitin) which targets specific proteins Sources of Amino Acids (A)Diet and (B)Cellular Proteins) Introduction

17. Amino Acid, Peptide And Protein Catabolism Introduction

18. Catabolism OF protein, amino acid - carbon skeleton AA can be group again to Glucogenic or Ketogenic amino acid Metabolism of the ( “carbon skeletons”)

19. Threonine Glycogenic, Ketogenic And Both Kitogenic And Glucogenic Amino Acids Classification

20. AMINO ACID DEGRADATION INTERMEDIATES CO 2 Pyruvate Acetyl-CoA Acetoacetate Citrate Isocitrate  -ketoglutarate Succinyl-CoA Fumarate Oxaloacetate Citric Acid Cycle CO 2 Glucose AlaSer CysThr* GlyTrp* Ile* Leu Trp Thr* Leu Trp* Lys Tyr* Phe* Asn Asp Phe* Tyr* Ile* Met Val Thr* ArgHis GluPro Gln Glucogenic Ketogenic * Both Glucogenic and Ketogenic Purely Ketogenic

21. Amino Acid Biosynthesis-- anabolism But most bacteria and plants can synthesize all amino acids. Nutritional classification of amino acid (AA); 1.essential (obtained from diet not synthesized in humans) 2. non-essential amino acid (synthesized in humans.)

22. Alanine Asparagine Aspartate Cysteine Glutamate Glutamine Glycine Proline Serine Tyrosine Arginine* Histidine Isoleucine Leucine Lysine Methionine Phenylalanine Threonine Tryptophan Valine Essential Nonessential * Arg is essential in infants and growing children but not in adults. 23 Nutritional classification of Essential and Nonessential Amino Acids in human

23. Nonessential amino acids are formed by 3 general mechanisms: ( 1)Transamination (TA) 2) Assimilation of free Ammonia 3) Modification of the carbon skeletons of existing amino acids.

24. Arginine – ornithine and urea cycle in adult Synthesis of Nonessential amino acids -summary

25. Alanine, can be synthesized by transamination of the corresponding α -keto acid =pyruvate. glutamate, can be synthesized by transamination of the corresponding α -keto acid, = α -ketoglutarate. aspartate can be synthesized by transamination of the corresponding α -keto acid = oxaloacetate (1)Transamination:

26. Serine is synthesized by the transamination and dephosphorylation of 3-phosphogylcerate, an intermediate of glycolysis.

28. ( 1)Glutamate: Formation of glutamate from ammonia and α-ketoglutarate is catalyzed by glutamate dehydrogenase. ( both synthesis and breakdown of glutamate) (2)Glutamine: Glutamine synthetase - ATP- dependent formation of glutamine, using glutamate and ammonia as substrates. b) Assimilation Of Free Ammonia:

29. glutamate dehydrogenase

30. Glutamine synthetase

31. Cysteine: Cysteine contains atoms donated by both methionine and serine. Glycine: Serine is also converted to glycine by the removal of its hydroxymethyl group. c ) Modification of the carbon skeletons of existing amino acids.

32. Tyrosine: Phenylalanine is hydroxylated to form tyrosine. Asparagine: Asparagine is synthesized by the transfer to the amide group of glutamine to the ß-carboxyl group of aspartate

33. Proline: Glutamate is reduced and cyclized to form proline.

34. Arginine – ornithine and urea cycle in adult Synthesis of Nonessential amino acids -summary