Metabolism of Amino Acids and Proteins

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Metabolism of Amino Acids and Proteins

• Digestion, Absorption
• Catabolism of Amino Acids
• Biosynthesis of Urea

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Proteins Classification

• Solubility
• Albumins (s. in water and salt sol.)
• Globulins (s. sparingly in water, s. in salt
  sol.)
• Prolamines (s. in 70-80 ethanol, Arg rich)
• Histones (s. in salt sol., basic)
• Scleroproteins (insoluble in water and salt sol.,
  Gly, Ala, Pro rich)

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Proteins Classification

• Shape
• Globular (albumins, globulins, enzymes)
• Fibrous (keratin, myosin, collagen, fibrin)
• Function
• Physical properties
• Electrophoretic mobility
• Sedimentation (ultracentrifugation)

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Proteins Structure

• Primary
• Secondary
• Tertiary
• Quarternary

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Primary structure

• Sequence of amino acids
• Peptide bond
• Encoded in DNA
• Determines higher structures

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20 Amino Acids
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Primary structure
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Secondary structure

• Spatial arrangement of AA chain
• Most stable structure - low energyall -NH
  groups bond to -CO- groups by hydrogen bonds
• Also maintained by hydorphobic interactions

• Within a single chain a-helix
• Between two chains b-pleated sheet
• parallel
• antiparallel
• Special type collagen helix

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Alpha helix
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Beta pleated sheet
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Tertiary structure

• Overall shape and folding pattern of polypeptide
  chain
• Bonds
• Disulphidic bridges
• Ion interactions
• Hydrophobic interactions
• Hydrogen bonds
• Energically most efficient

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Tertiary structure
Acidic proteinase
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Quarternary structure

• More polypeptide chains united by forces other
  than covalent bonds
• Hydrogen bonds
• Ion bonds
• Hydrophobic interactions

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Quarternary structure
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Metabolism
Food Proteins
Purins, pyrimidins, amines, pyrols etc
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Proteolytic enzymes

• Exo- or endopeptidases
• Inactive proenzymes
• Stomach
• pepsinogen --gt pepsin
• Endopeptidase
• Activated by acidic pH
• Preferentially splits Phe, Tyr, Glu and Asp bonds
• Pancreas (duodenum)
• trypsinogen --gt trypsin
• chymotrypsinogen --gt chymotrypsin
• Lys, Arg
• Karboxypeptidase A
• Karboxypeptidase B
• Enterocytes
• various aminopeptidases and dipeptidases

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General principles of AA reactions

• Decarboxylation
• Transamination
• Oxidative deamination
• Amonia transport and detoxication
• Urea synthesis
• Metabolism of carbon chain

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Vitamin B6 - pyridoxine

• water-soluble
• pyridoxal phosphate
• transamination reactions
• aldol cleavages
• de-aminations
• decarboxylations
• Schiff base linkage to the amino acid substrate

H2O
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Decarboxylation

• Catalysed by decarboxylases
• Cofactor pyridoxalphosphate
• R-CHNH2-COOH --gt R-CHNH2 CO2
• Not important for quantity
• Primary amines
• Biologically active amines
• Hormones, neurotransmiters, koenzymes
• Histamin (His), dopamin (dihydroxyPhe), serotonin
  (hydroxyTry), tyramin (Tyr), GABA (Glu) etc.

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Histamine
Serotonin
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Transamination

• Amino acids lose the amino groups by enzymatic
  removal via transaminases (or amino transferases)
  
• Transaminations occurs in vivo for all twenty
  primary amino acids except lysine and theonine
• Most transaminases require a-ketoglutarate to
  accept the amino group. 

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Transamination

• The transaminase reactions are all freely
  reversible
• Prosthetic group pyridoxal phosphate
• Reactions proceed through Schiff base
  intermediates
• ALT (liver, muscle), AST (myocardium, liver)

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Oxidative Deamination

• Glutamate formed by transamination reactions is
  deaminated to a-ketoglutarate
• Glutamate dehydrogenase - NAD or NADP is
  coenzyme
• Other AA oxidases - (liver, kidney) low activity

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Transport and detoxication of ammonia

• Ammonia has to be transported to liver
• Glutamine is the major transport form
• Glutamine serves as a source of amine groups for
  biosynthesis.

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Synthesis of urea

• Liver
• 5-step Urea Cycle (Small Krebs c., Krebs-Hensleit
  c., Ornitihin c.)
• Uses ammonia, CO2, 3 ATP and aspartate

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Step 1  Carbamoyl phosphate formation from
ammonia, bicarbonate and ATP

• Carbamoyl phosphate synthetase
• Liver cell mitochondrias
• Utilizes 2 ATP
• Requires Mg

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Step 2  Formation of citrulline from ornithine
and carbamoyl phosphate

• Ornithin transkarbamoylase
• Liver mitochondria
• Citrulline passes from mitochondrial membrane to
  cytosol

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Step 3  Formation of arginosuccinate from
citrulline and aspartate

• Argininosuccinate synthetase
• Requires ATP and Mg

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Step 4  Formation of arginine and fumarate from
arginosuccinate

• Argininosuccinase
• Liver and kidney of mammals
• Fumarate is metabolised in Citric Acid Cycle
  (thus aspartate could be regenerated)

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Step 5  Hydrolysis of arginine to form ornithine
and urea

• Ornithine regenerated, urea produced
• Urea excreted (N rich, excelent solubility,
  harmless gt worth 3 ATP -))

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Carbon chain fate

• All twenty common amino acids are converted to
  only seven compounds
• 1.  Pyruvate
• 2.  Acetyl CoA
• 3.  Acetoacetyl CoA
• 4.  alpha-Ketoglutarate
• 5.  Succinyl CoA
• 6.  Fumarate
• 7.  Oxaloacetate

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Glycine and all three-carbon amino acids are
converted to pyruvate

• Glycine used for synthesis of creatine,
  porphyrines, purines, glutathion
• Serine decarboxylation gt ethanolamine gt
  methylation to choline
• Threonine and tryptophan are essential AA

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Four-carbon amino acids are converted to
oxalacetate
Five-carbon amino acids are converted to
alpha-ketoglutarate
Histamine GABA
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Methionine, isoleucine and valine are converted
to succinyl CoA

• All essential
• Methionin could be metabolised to cystein

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AA degraded to acetyl CoA and acetoacetyl CoA are
called "ketogenic"

• Phenylalanine, leucine and lysine are essential
• Ketone bodies - acids which can cause a decrease
  in blood pH
• Ketoacidosis

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Degradation of phenylalanine and tyrosine are
unique

• Series of reactions follows that deaminates
  tyrosine via transamination and ultimately leads
  to trans-fumarate and acetoacetate using molecule
  oxygen to break the aromatic ring
• Phenylketoneuria
• Thyroxin, epinephrin, NE, dopamin, tyramin,
  melanin

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Used material Gary O. Gray, Ph.D.

• http//www.sbuniv.edu/ggray.wh.bol/CHE3364/b1c25o
  ut.html