The document discusses protein and amino acid metabolism. It covers: 1. The digestion of proteins into amino acids in the stomach and small intestine by enzymes like pepsin and trypsin. 2. The 20 standard amino acids and their classification as essential/non-essential and glucogenic/ketogenic. 3. The transport of amino acids in blood to cells and their role in protein synthesis and degradation via ubiquitination and proteasomes.

1. Mahmoud Balbaa
Professor of Biochemistry
Beirut Arab University
March 2012

2. Dynamics of Protein
And Amino Acid Metabolism
Dietary Proteins Digestion to Amino Acids
Transport in Blood to Cells
Protein Synthesis Functional Proteins
Amino Acids Protein Degradation In
Proteasomes Following
Tagging With Ubiquitin
Metabolites
2

3. Digestion of Proteins
Stomach: Pepsinogen Pepsin (max. act. pH 2)
Enteropeptidase
Small Intestine: Trypsinogen Trypsin
Trypsin cleaves:
Chymotrypsinogen to chymotrypsin
Proelastase to elastase
Procarboxypeptidase to carboxypeptidase
Aminopeptidases (from intestinal epithelia)
3

4. 20 Amino Acids

5. Metabolic Classification of the
Amino Acids
• Essential and Non-essential
• Glucogenic and Ketogenic
5

6. Non-Essential Amino Acids in
Humans
 Not required in diet
 Can be formed from α-keto acids by
transamination and subsequent
reactions• Alanine • Glycine
• Asparagine • Proline
• Aspartate • Serine
• Glutamate • Cysteine (from Met*)
• Glutamine • Tyrosine (from Phe*)
* Essential amino acids
6

7. Essential Amino Acids in
Humans
 Required in diet
 Humans incapable of forming requisite
carbon skeleton
• Arginine* • Lysine
• Histidine* • Methionine
• Isoleucine • Threonine
• Leucine • Phenylalanine
• Valine • Tryptophan
* Essential in children, not in adults
7

8. Glucogenic Amino Acids
 Metabolized to α-ketoglutarate,
pyruvate, oxaloacetate, fumarate, or
succinyl CoA
Phosphoenolpyruvate Glucose
• Aspartate • Methionine • Alanine
• Asparagine • Valine • Serine
• Arginine • Glutamine • Cysteine
• Phenylalanine • Glutamate • Glycine
• Tyrosine • Proline • Threonine
• Isoleucine • Histidine • Tryptophan
8

9. Ketogenic Amino Acids
 Metabolized to acetyl CoA or
acetoacetyl CoA
Animals cannot convert acetyl CoA or
acetoacetyl CoA to pyruvate
• Isoleucine • Tryptophan
• Leucine * • Phenylalanine
• Lysine * • Tyrosine
• Threonine
* Leucine and lysine are only ketogenic
9

10. 5. Carbon Atoms
Ketogenic Glucogenic Both
leucine serine isoleucine
lysine threonine phenylalanine
aspartic acid tryptophan
glutamic acid tyrosine
asparagine
glutamine
glycine
alanine
valine
proline
histidine
arginine
methionine
cysteine
10

11. 4. The Urea Cycle
11

12. Urea Formation
 Occurs primarily in liver; excreted by
kidney
 Principal method for removing ammonia
 Hyperammonemia:
 Defects in urea cycle enzymes (CPS, OTC,
etc.)
 Severe neurological defects in neonates
 Treatment:
 Stop protein intake
 Dialysis
 Increase ammonia excretion: Na benzoate, Na
phenylbutyrate, L-arginine, L-citrulline
12

13. Blood Urea Nitrogen
 Normal range: 7-18 mg./dL
 Elevated in amino acid catabolism
 Glutamate N-acetylglutamate
CPS-1 activation
 Elevated in renal insufficiency
 Decreased in hepatic failure
13

14. 5. Carbon Atoms
14

15. Alkaptonuria
• Deficiency of homogentisate dioxygenase
• Urine turns dark on standing
• Oxidation of homogentisic acid
• Asymptomatic in childhood
• Tendency toward arthritis in adulthood
15

16. Serotonin
• Serotonin formed in:
• Brain (neurotransmitter; regulation of sleep, mood, appetite)
• Platelets (platelet aggregation, vasoconstriction)
• Smooth muscle (contraction)
• Gastrointestinal tract (enterochromaffin cells - major storage site)
• Drugs affecting serotonin actions used to treat:
• Depression
•Serotonin-selective reuptake inhibitors (SSRI)
• Migraine
• Schizophrenia
• Obsessive-compulsive disorders
• Chemotherapy-induced emesis
• Some hallucinogens (e.g., LSD) act as serotonin agonists
16

17. 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)

18. Proteins : Classification
 Shape
 Globular (albumins, globulins, enzymes)
 Fibrous (keratin, myosin, collagen, fibrin)
 Function
 Physical properties
 Electrophoretic mobility
 Sedimentation (ultracentrifugation)

19. • Primary
• Secondary
• Tertiary
• Quarternary

20. Primary structure
 Sequence of amino acids
 Peptide bond
 Encoded in DNA
DNA mRNA protein
 Determines higher structures

21. Primary structure

22. Secondary structure
 Spatial arrangement of AA chain
 Most stable structure - low energy:
all -NH groups bond to -CO- groups by hydrogen
bonds
 Within a single chain: α -helix
 Between two chains: β-pleated sheet
o parallel
o antiparallel
 Special type: collagen helix
 Also maintained by hydorphobic interactions

23. Alpha helix

24. Beta pleated sheet

25. Tertiary structure
 Overall shape and folding pattern of
polypeptide chain
 Bonds
 Disulphidic bridges
 Ion interactions
 Hydrophobic interactions
 Hydrogen bonds
 Energically most efficient

26. Tertiary structure
Acidic proteinase

27. Quarternary structure
 More polypeptide chains united by forces
other than covalent bonds
 Hydrogen bonds
 Ion bonds
 Hydrophobic interactions

28. Quarternary structure