The Big Picture of Protein Metabolism

Gladys Kaba

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INTRODUCTION- General Structure of Amino acid (AA)

Carboxylic acid

Acetic acid

Amino acid (AA)

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)

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The 21 Different Amino Acids(AA) Can Be classified into -----

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Abbreviations and symbols of Amino acids

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Dipeptide , tetrapeptides, pentapeptides, etc few amino acids are joined ------

oligopeptide. many amino acids are joined----- polypeptide

(protein usually >50 amino acids)

PEPTIDE AND PROTEIN

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Levels of Protein Structure

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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

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Alpha helix

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1. Hydrophobic interactions 2. Hydrophilic interactions 3. Salt bridges 4. Hydrogen bonds5. Disulfide bonds

3. Tertiary structure: additional folding and additional bond

formation which may involve--

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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.

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Denaturation

Protein Hydrolysis / Denaturation

A protein or peptide can be hydrolyzed into individual amino acids.

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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

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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

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

(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

Amino Acid , Peptide And Protein Catabolism

Introduction

Catabolism OF protein, amino acid -

carbon skeleton AA can be group again to Glucogenic or Ketogenic amino acid

Metabolism of the ( “carbon skeletons”)

Threonine

Glycogenic , Ketogenic And Both Kitogenic

And Glucogenic Amino Acids Classification

AMINO ACID DEGRADATION INTERMEDIATES

CO2

CO2

Pyruvate

Acetyl-CoA Acetoacetate

Citrate

Isocitrate

a-ketoglutarateSuccinyl-CoA

Fumarate

Oxaloacetate

CitricAcidCycle

CO2

Glucose

Ala SerCys Thr*Gly Trp*

Ile*Leu•

TrpThr*

Leu• Trp*Lys• Tyr*Phe*

AsnAsp

AspPhe*Tyr*

Ile*MetValThr*

Arg HisGlu ProGln

Glucogenic

Ketogenic

* Both Glucogenic and Ketogenic

• Purely Ketogenic

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.)

AlanineAsparagineAspartateCysteineGlutamateGlutamineGlycineProlineSerineTyrosine

Arginine*HistidineIsoleucineLeucineLysineMethioninePhenylalanineThreonineTryptophanValine

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

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.

Arginine – ornithine and urea cycle in adult

Synthesis of Nonessential amino acids -summary

• Alanine, can be synthesized by transamination of thecorresponding α -keto acid =pyruvate.

• glutamate, can be synthesized by transamination of thecorresponding α -keto acid, = α -ketoglutarate.

• aspartate can be synthesized by transamination of thecorresponding α -keto acid = oxaloacetate

(1)Transamination:

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

(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:

glutamate dehydrogenase

Glutamine synthetase

• 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.

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

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

Arginine – ornithine and urea cycle in adult

Synthesis of Nonessential amino acids -summary