Biology of Disease

O

H

...N ...

Endopeptidase

activity

CH

R

C

O

CH

R

N CH C

R

C

O

H H

N

B)

Figure 11.14The sites of digestion (hydrolysis) of proteins by (A) exopeptidase and (B) endopeptidase activities.

Figure 11.15Model of the enzymatically active

form of a pancreatic lipase molecule. PDB file 1N8S.

Zymogen Activation mechanism Active enzyme

Pepsinogen HCl, pepsin pepsin

Trypsinogen enteropeptidase (enterokinase) trypsin

Proelastase trypsin elastase

Chymotrypsinogen trypsin chymotrypsin

Procarboxypeptidase trypsin carboxypeptidase

Proaminopeptidase trypsin aminopeptidase

Table 11.2Zymogens

X]VeiZg&&/ DISORDERS OF THE GASTROINTESTINAL TRACT, PANCREAS, LIVER AND GALL BLADDER

'-- W^dad\nd[Y^hZVhZ

CH

R

N CH C

R O-

C

O

O

H+ 3 NCH

R

N CH C

R

C

O O

H H H

... N

Exopeptidase

activity

Exopeptidase

activity

A)

enters the small intestine through the pancreatic duct. The salts neutralize

acid from the stomach.

Proteolytic enzymes can be divided into exopeptidases and endopeptidases.

The exopeptidases are aminopeptidases and carboboxypeptidases that cata-

lytically remove amino acids from the ends of proteins and peptides (Figure

11.14(A)). The pancreatic proteases, elastase, trypsin and chymotrypsin, are

endoproteases (Figure 11.14(B)) and hydrolyze proteins and peptides at dif-

ferent peptide bonds throughout the molecules to produce peptides and

amino acids. The actions of endopeptidases increase the number of protein

ends, effectively increasing the concentration of substrates for the exopepti-

dases. Pancreatic amylase continues the digestion of polysaccharides to pro-

duce disaccharides. Pancreatic lipase (Figure 11.15) hydrolyzes lipids to fatty

acids and 2-monoacylglycerols but requires the presence of colipase, another

protein secreted by the pancreas, for full activity. Bile released from the gall

bladder enters the intestine through the bile duct and emulsifies lipids into

droplets of about 1 Lm diameter, which greatly increases the surface area

available for lipase activity. Pancreatic esterase activity can complete the

digestion to glycerol and free fatty acids (Figure 11.16).

The activities of many of the enzymes involved in digestion are summarized

inTable 11.3.