Amino Acid Metabolism I

Precursors of Proteins
or
Nutrients
Amino Acid Metabolism
 Proteins
(Amino Acids)

Only 20 naturally-occurring amino acids

Standard Amino Acids (20)
Dipolar Ions
(Zwitterions)
Nonpolar and Hydrophobic
Amino Acids I
Nonpolar and Hydrophobic
Amino Acids II
Polar Amino Acids I
Polar Amino Acids II
Acidic Amino Acids
Basic Amino Acids
Notation for 20 Standard AAs
 Greek Nomenclature

Figure 4-8
 Protein Digestion

Dietary Proteins

Proteins ——> Amino Acids

 Proteolytic Enzymes
(Synthesized in the Pancreas)

• Pepsin
• Trypsin
• Chymotrypsin
• Elastase
• Carboxypeptidases A and B
• Aminopeptidases
• Di- and Tri-peptidases
 The Problem

How to prevent proteolytic

enzymes from acting
prematurely and degrading the
pancreas.
The Solution: Zymogens

Somewhat larger “inactive”

precursors
 Zymogens

• Trypsinogen: Trypsin
• Chymotrypsinogen: Chymotrypsin
• Proelastase: Elastase
• Procarboxypeptidases: Carboxypeptidases
A and B

• Prophospholipase A2: Phospholipase A2

 Acute Pancreatitus

Cause: premature activation of

digestive enzymes synthesized by the
pancreas.
Symptoms: acute pain and sometimes
death.
 Trypsin-BPTI Complex

Figure 11-31a
Hormones Control Secretion of
Zymogens from Mucosa of the
Duodenum (Upper Intestine)
Activation of Trypsinogen to
Trypsin
 Trypsin completes its own
activation (autocatalytic)

Trypsin activates other inactive

precursors
Protein Digestion
Amino Acid Digestion and Uptake
Amino Acid Uptake
Mechanism of Serine
Proteases
Chymotrypsin
Trypsin
Elastase
etc.
Reaction of Chymotrypsin

R1 = Phe, Tyr or Trp

Reaction of Chymotrypsin
Kinetic Analysis of Chymotrypsin
(Hydrolysis of p-nitrophenylacetate)
Mechanism of Chymotrypsin

p-nitrophenolate
Identification of the Catalytic Residues
(Reaction of Chymotrypsin with DIPF)

Special Reactivity of Serine195

Identification of the Catalytic Residues
(Reaction of Chymotrypsin with TPCK)

Affinity Labeling
(Localization of His 57 in Active
Site)
X-Ray Structure of Bovine Trypsin
(Ribbon Diagram)
Active Site Residues of Chymotrypsin
(Catalytic Triad)
 Catalytic Mechanism of the
Serine Proteases

Catalytic Triad
Catalytic Mechanism of the
Serine Proteases
Catalytic Mechanism of the
Serine Proteases
Catalytic Mechanism of the
Serine Proteases
Catalytic Mechanism of the
Serine Proteases
Catalytic Mechanism of the
Serine Proteases
Transition State Stabilization in
the Serine Proteases
Transition State Stabilization in
the Serine Proteases
Summary of Intestinal Proteolysis
and Amino Acid Transport

• Cleavage of dietary proteins

• Uptake of amino acids into intestinal
epithelial cells
• Transport of amino acids into the blood
• Transport of dietary amino acids to tissues
and organs
• Uptake of amino acids into cells
Catabolism of Amino Acids
Catabolism of Amino Acids