GASTROENTEROLOGY Vol. 61, No.

4, Part 1
Copyright © 1971 by The Williams & Wilkins Co. Printed in U.S. A.

PROGRESS IN GASTROENTEROLOGY

PROTEIN DIGESTION AND ABSORPTION

GARY M. GRAY, AND HERBERT L. CooPER

Division of Gastroenterology, Stanford University School of Medicine, Stanford,

California, and Division of Gastroenterology, University Hospital,
Boston, Massachusetts

The processes whereby protein is di- functionally from each other only in their
gested and absorbed are not as well under- specificity for particular amino acids. The
stood as are those for other nutrients but, principal exopeptidases are the carboxy-
nevertheless, a great deal of information peptidases which act on terminal peptide
has come forth in the last few years. As has bonds at the carboxyl (COOH) end of pro-
been true in the study of assimilation of tein chains. Both the endo- and exopepti-
carbohydrates and fat, the focus of interest dases are synthesized in the pancreatic
has been on the function of the intestinal acinar cells and then secreted as inactive
cell and its role in transporting the amino precursors via the pancreatic ducts into
acid products of digestion. the upper duodenal lumen where activa-
Despite this, it is important to consider tion occurs by a specific scission of the pro-
the over-all processes of digestion and ab- tein molecule.
sorption and this review considers both the Keller's comprehensive review 7 of the
pancreatic and small intestinal phases of activation, structure, and specificity of
protein digestion and absorption. pancreatic proteases may be useful to the
reader. wishing more details than are pro-
Pancreatic Enzyme Secretion vided below.
More than 20 years ago several of the
proteolytic enzymes had been isolated in Intraduodenal Activation of Pancreatic
essentially pure form from bovine and por- Pro teases
cine pancreas, ,_ 3 and it was determined Endopeptidases. Although the majority
that the proteases were secreted into the of data available on the pancreatic prote-
duodenum as inactive precursors. Since ases has come from study of the bovine and
then, the actual structure of many of these porcine enzymes, differences from species
enzymes in both the proenzyme and active to species appear to be small and man can
state has been elucidated. 4 - 6 be expected to possess very similar struc-
There are two general classes of pan- tures for the enzymes.
creatic proteases. The endopeptidases As outlined in figure 1, the proenzymes
trypsin, chymotrypsin, and elastase attack or zymogens are secreted into the duodenal
the interior peptide (CO-NH) bonds be- lumen where initial activation of trypsino-
tween adjacent amino acids and differ gen is catalyzed by enterokinase, an enzyme
located on the surface of the duodenal mu-
Received October 17, 1969. cosa. 8 The exact structure of this activating
Address requests for reprints to: Dr. Gary M. Gray,
protein is unknown, but it splits a fragment
Division of Gastroenterology, Stanford University
School of Medicine, Stanford, California 94305.
from the amino terminal end of the tryp-
This work was supported by United States Public sinogen molecule by hydrolyzing the pep-
Health Service Grant AM11270. tide bond between lysine-6 and isoleucine-7
Dr. Gray is a recipient of Research Career Develop- thereby releasing a hexapeptide and the
ment Award 1-K4-AM-47,443. active trypsin (fig. 2). After this initial acti-
535
536 PROGRESS IN GASTROENTEROLOGY Vol. 61, No.4, Part 1

Vol1 - - L y s 6
vation, the active trypsin acts autocatalytic-
Voi1-Lys 6fi1o 7)
ally in the same way as enterokinase to
activate the bulk of the trypsinogen. As
C
ENTEF«>I<JNASE
TRYPSIN
c
outlined in figure 1, trypsin then activates ' - - - - - Asn 2 29 ' - - - - - Asn 229
TRYPSINOGEN
all of the other precursor peptidases of the
pancreas including chymotrypsinogen, pro-
elastase, and the procarboxypeptidases. Cys 1 - - ArQ t5 flle 16 Cys 1- - A r g 15

Chymotrypsinogen, being very similar L. ,22 J~ cL..22-~~· ··

in structure to trypsinogen, 7 is activated by
relatively small amounts of trypsin (one part c -=
CHYMOTRYPSINOGEN 11 CHYMOTRYPSIN
--
in 70) 9 which splits the CO- NH bond be-
FIG. 2. Diagram of the mechanism of activation
tween arginine-15 and isoleucine-16 (fig.
10 of bovine pancreatic proenzymes. Abbreviations for
7
2). Although a structural rearrangement amino acids units are: Val, valine; Lys, lysine; Ile, iso-
then occurs, no peptide fragments are leucine; Asn, asparagine; Cys, Cysteine. The number-
actually released because there is a disul- ing refers to the position on the protein chain beginning
fide bond between cysteine-1 and cysteine- at the N-terminal amino acid.
122 (fig. 2). This form of the enzyme is
called 1r-chymotrypsin. Secondary cleav- activation of the exopeptidases is still rela-
ages at other parts of the molecule also tively rudimentary. The exact alteration
occur by autocatalytic means producing in their structure that is necessary for acti-
the other species (usually termed a and vation is not known. Under physiological
{3) of chymotrypsin with relatively less conditions of temperature and trypsin con-
activity which may not play a physiolog- centration, carboxypeptidase A is formed
ical role in protein digestion. when its parent zymogen procarboxypep-
Proelastase, the inactive zymogen, be- tidase A is extensively degraded by the
comes activated by trypsin to elastase, an action of trypsin. The active carboxypep-
enzyme with broad specificity against in- tidase A is only about one-third the size of
terior peptide bonds of proteins and the its precursor. I I
only protease that can attack elastin (fig. Procarboxypeptidase B is also activated
1). Although the exact mechanism of acti- by trypsin but, unlike the other active exo-
vation is unknown, the amino acid sequence peptidase, carboxypeptidase B is either
of the active enzyme itself has recently the same molecular size (during early acti-
been elucidated. 6 Its structure is remark- vation) or slightly smaller (second phase of
ably similar to trypsin and chymotrypsin. activation) than its zymogen precursor. I 2
The differences in specificity of these
three types of endopeptidases is outlined Substrate Specificity of Pancreatic
below and appears to occur because of a Pro teases
few selective amino acid differences at Because of the restricted site of action
the substrate sites accompanied by exten- of many of the proteases, protein digestion
sive but relatively unimportant substitu- occurs only by virtue of a sequential action
tions at other portions of the enzyme. 6 of specific endopeptidase and exopeptidase
Exopeptidases. Information about the (fig. 3). Hence trypsin hydrolyzes protein
to peptides only at locations of the basic
PROENZYME ENZYME amino acids thereby yielding peptides with
[NT[ROKINASE
only arginine or lysine on the carboxyl ter-
I
TRYPSINOGEN TRYPSIN

TRYPSIN minal end of the molecule. 13 Carboxy-

CHYMOTRYPSINOGEN CHYMOTRYPSIN
peptidase B can then hydrolyze the single
PROELASTASE
lTRYPSIN

ELASTASE arginine or lysine from the C-terminal po-

PROCARBOXYPEPTIOASE
I CARBOXYPEPTIDASE
TRYPSIN sition since it has high specificity for these
basic amino acids. 14
FIG. 1. Activation of the pancreatic proteases in the On the other hand, chymotrypsin acts
duodenal lumen. Modified from Keller. 7 interiorly at aromatic amino acid sites to
October 1971 PROGRESS IN GASTROENTEROLOGY 537
produce peptides with a C-terminal phenyl- across the luminal cell boundary to be hy-
alanine, tyrosine, or tryptophan; in addi- drolyzed by intracellular enzymes. How-
tion some chymotrypsins also have speci- ever, recent studies of the brush border
ficity for leucine, glutamine, and methio- and intracellular enzymes indicate that
nine. 15 Elastase has the broadest specificity the brush border enzymes are distinctly
of any endopeptidase acting particularly different from the intracellular pepti-
on the aliphatic (nonpolar) amino acids dases, 21 · 22 and the soluble peptidases ap-
such as valine, leucine, serine, and alanine pear to be no different than enzymes that
to produce peptides with these amino acids occur within cell sap of many other or-
at the carboxy-terminus. 6· 16 These aroma- gans. 22, 23
tic and aliphatic C-terminal peptides pro- Intracellular peptidases. Nevertheless,
duced by chymotrypsin and elastase are the intracellular (soluble) peptidases prob-
ideal substrates for carboxypeptidase A, 7 ably have the capacity to hydrolyze small
which hydrolyzes the neutral amino acid peptides that enter the cell in intact form.
from the C-terminus. The bulk of the work on intestinal pepti-
Figure 3 outlines the concerted action of dases in animals and man has been on these
pancreatic endopeptidases and exopepti- soluble enzymes that are located in the
dases. cell cytoplasm and account for about 80%
of the total mucosal activity of most peptide
Intestinal Oligopeptidases: Brush
hydrolases that have been studied. 18· 19· 24 -27
Border and Intracellular
There appear to be four to eight enzymes
Like the disaccharidases, enzymes hy- separable by starch gel electrophoresis that
drolyzing small peptides are present in only can hydrolyze various dipeptides and tri-
trace amounts in pancreatic or intestinal peptides. 28 Whereas glycine- and leucine-
secretions' 7 and appear to be confined to containing peptides have been studied most
the intestinal surface cell. 18 · 19 There has extensively, other peptides containing an
been much controversy concerning the di- aliphatic or aromatic neutral amino acid
gestion and absorption of the smaller mo- are readily hydrolyzed by these soluble
lecular products of pancreatic enzyme di- enzymes. (Naturally occurring amino acids
gestion. A principal reason for this is the in dietary protein are structurally of the
finding of oligopeptidases both in the in- L-form. We have chosen to omit the desig-
terior of the small intestinal columnar cell' 8 nation, but whenever an amino acid is
as well as within its luminal brush border, 20 mentioned in peptide or in free acid, it
making it difficult to determine whether indicates the L isomer rather than the D
the small peptides are split on the outer sur- isomer.) In addition, there are soluble
face of the intestinal cell or transported peptidases that hydrolyze glycyl-gly-
cine 19 · 25 and dipeptides containing pro-
ENDOPEPTIDASES EXOPEPTIDASE$
line29 as well as an enzyme that is highly
BASIC
specific for N-terminal arginine or lysine. 24
At g!IC,oC · TEII- ~
AMINO ACIDS Brush border peptidases. Although the
TRYPSIN PEPTIOES CAfiBOXYPEPTIOASE 8
brush border peptidases have not yet been
studied extensively, 10 to 20 ~c of intestinal
dipeptidase activity is known to be present
in the microvillar membrane. 20 · 30 These
CHYMOTRYPSIN
AIIOioiATIC C·f(IUIIHAl SMALL PEPTIOES
PROTEIN PEPTIOES

CARBOXYPEPTIDASE A
enzymes appear to be distinctly different
proteins than those found in soluble
ELASTASE
PEPTIOES
NEUTRAL
AMINO ACIDS form. 21 · 22 Recently three brush border
FIG. 3. lntraduodenal sequential action of pancre-
peptidases have been separated and char-
atic endopeptidases and exopeptidases on dietary pro- acterized in the rat with specific activities
tein. The final products on the right are the substrates averaging 10 times higher than those found
which must be handled by the intestinal cell. Arg, argi- for the intracellular enzymes (F. Wojnarow-
nine; Cys, cysteine. ska and G. M . Gray, unpublished observa-
538 PROGRESS IN GASTROENTEROLOGY Vol. 61, No.4, Part 1

tions). Two of these show specificity for tion of the composition of intestinal con-
dipeptides, tripeptides, and tetrapeptides tents after oral intake of protein, Nixon
composed of neutral amino acids on the and Mawer 32 • 33 demonstrated that man
amino-terminal end with maximal activity hydrolyzes milk or gelatin within 15 min to
exerted against the tripeptides. These are 30 to 50% free amino acids and small pep-
probably best termed oligopeptidases. tides with the remainder of the products
The other major brush border peptidase being in the form of large peptides and pro-
seems to be a true dipeptidase that has tein. The same fractional distribution pat-
minimal specificity for larger oligopeptides. tern continues during the digestion process
Like the oligopeptidases, it acts preferen- for at least 2 hr as the meal moves well down
tially against dipeptides composed of neu- into the jejunum. The vast majority of the
tral amino acids, particularly glycyl-leucine milk or gelatin meal is hydrolyzed and ab-
and leucyl-glycine. Activity against proline- sorbed by the time the meal reaches the
containing peptides is absent for all three distal jejunum. Interestingly enough, only
of these enzymes. certain amino acids are readily released in
Hence, different peptidases appear to the free form. Appreciable amounts of the
be strategically located for digestion both basic amino acids (arginine, lysine) and neu-
in the brush border and within the intra- tral amino acids (valine, phenylalanine, ty-
cellular fluid. Like the disaccharidases, rosine, methionine, leucine) are released to
the brush border peptidases are ideally be transported by the intestinal cell. In con-
located at the intestinal mucosa-lumen in- trast, glycine, the imino acids (proline, hy-
terface and have specificity appropriate droxyproline), the hydroxyl-substituted
for small peptides composed of neutral amino acids (serine and threonine), and the
amino acids. However, the brush border dicarboxylic amino acids (aspartic and glu-
enzymes seem incapable of rapidly hydro- tamic) continue to remain about 90Sr pep-
lyzing proline and hydroxyproline peptides tide linked in the intestinal lumen until
or arginyl and lysyl peptides whereas the they disappear and hence probably enter
intracellular peptidases are more active the intestinal cell as constituents of small
against these substrates 24 • 29 making it peptides; the alternative explanation of hy-
likely that the cell surface and the interior drolysis of such oligopeptides by brush
cytoplasm play a complementary role m border surface enzymes followed by com-
digestion of the oligopeptides. plete capture by the amino acid transport
mechanisms seems highly unlikely since
Digestion of Dietary Protein: In surface digestion of nutrients is known to
Vivo Studies be associated with considerable diffusion
Whether oligopeptides and dipeptides of released products such as hexoses 3 4 or
enter the intestinal cell in intact form or amino acids 35 • 36 back into the intestinal
rather are initially hydrolyzed to amino fluids .
acids can only be interpreted in the light Other studies in both animals 36 • 37 and
of physiological experiments. man 38 have compared absorption from solu-
Previous studies in animals and man 3 1 tions of peptides to that of equivalent amino
had suggested that an appreciable fraction acid mixtures, particularly by use of gly-
of the protein in intestinal contents after a cine peptides (glycyl-glycine and glycyl-
meal was made up of endogenous proteins. gylcyl-glycine) and glycine. Evidence
More recent experiments in man 32 • 33 pro- clearly indicates that glycine is absorbed
vide convincing evidence that 65 to 90S;, more rapidly from the dipeptide and tri-
of the postprandial intraintestinal protein peptide, suggesting that the small peptides
is exogenous in its origin making it much probably enter the cell at rates comparable
more feasible to interpret in vivo absorp- to the amino acid, presumably at the same
tion studies by determining the degree of entry sites. 37 Thus three molecules of
disappearance of protein and the size of glycine can move into the cell more effi-
residual peptides. ciently at a specific entry site as constitu-
As estimated from a thorough examina- ents of a single tripeptide molecule rather
October 1971 PROGRESS IN GASTROENTEROLOGY 539

than as three molecules of the amino acid. cellular peptidases appear to play a role in
Supporting the absorption of intact glycine oligopeptide digestion, the site of hydroly-
peptides is the finding that intestinal pep- sis depending on the types of amino acids
tidase activity against them in the brush and probably their location in small pep-
border is only 1% of the sucrase activity. 20 tides.
In vitro studies of isolated rat intestine also Transport mechanisms for amino acids
show absorption of intact gylcine peptide are considered further below, but the re-
followed by intracellular hydrolysis of 90% cent protein meal studies in man 32· 33
and exit of 10% from the cell as intact strongly suggest that only the neutral amino
dipeptide. 39 Recently, this has been cor- acids and the two basic amino acids argi-
roborated in vivo in the rat 40 by demonstra- nine and lysine are quantitatively taken in
tion of glycyl-glycine in portal venous blood as amino acids. The imino acids (proline
at concentrations 4 to 8% of that for glycine and hydroxyproline), glycine and the dicar-
during absorption of ~lycine peptides. De- boxylic acids (glutamic and aspartic) all
spite these interesting studies with oligo- appear to enter as constituents of small pep-
peptides of glycine, dietary protein rarely tides, where specific intracellular pep-
contains a series of glycine residues and tides42 can hydrolyze them.
the physiological importance of such oligo- Figure 4 diagrams the major mechanisms
peptide absorption is uncertain. Analogous by which the intestinal cell appears to ac-
to the findings for glycine peptides, about commodate small peptides and amino acids.
10% of a gelatin meal is excreted in human Whereas neutral peptides are hydrolyzed
urine as unhydrolyzed hydroxyproline pep- readily by brush border peptidases, par-
tide, 41 reflecting the appreciable absorp- ticularly if a neutral amino acid is located
tion of intact peptides that can occur when at the amino-terminal position, some of
they are composed of certain amino acids. these appear capable of entering the cell
In contrast to these findings for glycine intact 43 and peptides containing mainly
and hydroxyproline peptides, recent stud- glycine residues or proline and hydroxypro-
ies in the rat with methionine and the di- line residues appear to enter the cell intact
and tripeptides containing methionine for lack of brush border peptidases; intra-
have shown that absorption from the pep- cellular enzymes then reduce these to
tide is identical to that for the equivalent amino acids (90%) but approximately lO ~o
amino acid solution as long as physiologi- of absorbed glycine or proline peptides
cal concentrations (50 mM amino acid leave the intestinal cell in peptide form
equivalent or less) are used. 35 Furthermore, (fig. 4). A mixed peptide containing differ-
high concentrations of free methionine ac- ent types of amino acids may utilize more
cumulate in the intestinal luminal contents than one entry mechanism depending on
during methionyl-methionyl-methionine its relative affinity for specific cell trans-
absorption suggesting that hydrolysis of port or brush border hydrolytic systems.
the tripeptide occurs at the intestinal brush Arginine and lysine residues in protein be-
border surface so rapidly that the methi- come positioned on the C-terminus of pep-
onine transport mechanism cannot accept tides produced by trypsin and are split
all of the released amino acid. Hence, in . off by carboxypeptidase B to the free amino
the case of methionine-containing peptides, acids. Hence absorption of these dibasic
hydrolysis of the peptide occurs very rap- amino acids probably does not occur m
idly at the brush border and absorption is peptide form.
mainly, if not entirely, in the form of the Transport of Amino Acids
amino acid. Previous reviews •... 6 have carefully
considered the various intestinal transport
Schema for Intestinal Peptide systems and table 1 briefly lists them along
Digestion and Absorption with their distinguishing characteristics.
Based on the cellular location of the vari- The neutral amino acid mechanism ap-
ous peptidases and intubation experiments pears to be the functionally most important
in man, both the brush border and intra- transport system and has been extensively
540 PROGRESS IN GASTROENTEROLOGY Vol. 61, No.4 , Part 1

PORTAL
~

IMINO
PROLINE
PEPTIDASE
90"
HYDROXY·
PROLINE
--......,1---...
' 10'%
'- SMALL
)--.PEPTIDES--- - - -
/'lo"'

FIG. 4. Outline of the major routes of oligopeptide and amino acid entry into the intestinal cell. The peptides
probably average three to four amino acid residues. Pro, proline; Gly , gylcine.

TABLE 1. Intestinal amino acid transport mechanisms

Type Am ino ac ids t ransported T ype of 1ransport Relati ve rate

Neutral (monoamino- Aromatic (tyrosine, tryptophan, phenyl- Active, Na +-depen- Very rapid
monocarboxylic) alanine dent
Aliphatic (glycine, a alan ine, serine,
threonine, valine, leucine, isoleucine)
Methionine, histidine, glu tamine, a spa-
ragine, cysteine
Dibasic (diamino) Lysine, arginine, ornithine, cystine Active, partially Na +- Rapid (10' i
dependent of neutral)
Dicarboxylic (acidic) Glutamic acid, aspartic acid Carrier-mediated, Rapid
?active, partially
Na +-dependent
Imino acids and glycine Proline, hydroxyproline, glycine" Active, ?Na •-depen- Slow
dent

a Shares both the neutral and imino mechanism with low affinity for the neutral.

studied. It is lmown to be an active process attached to the a-carbon is mandatory for

that will move the amino acid uphill against active neutral amino acid transport and
a cell to lumen concentration gradient. 47 affinity is greatly increased when the a-
Na + is required 48 • 49 and kinetic studies NH2 is unsubstituted and the side chain at-
strongly suggest that a ternary complex of tached to the a-carbon is nonpolar (ali-
amino acid, Na +, and membrane carrier phatic). 47 Intestinal perfusion experiments
(presumably a protein) is formed thereby in man have shown maximal rates of absorp-
permitting entry and release beyond the tion in jejunum 51 as well as competition
outer cell barrier. 50 Na + then appears to be between glycine and alanine, 52 indicating
actively extruded from the cell to the lat- that they share the neutral transport
eral intercellular spaces thereby providing mechanism. Another study, using an equi-
the driving force for so-called active amino molar mixture of eight neutral amino acids
acid transport. An intact carboxyl group demonstrated relative absorption rates to
October 1971 PROGRESS IN GASTROENTEROLOGY 541

be methionine > isoleucine > leucine > Interactions of Amino Acids and
valine > phenylalanine > tryptophan > Hexoses:A Single Transport
threonine, 53 corroborating the affinity re- Mechanism?
quirements previously established in vitro The actively absorbed sugars D-glucose
in animals. and D-galactose have recently been shown
The dibasic amino acids and cystine are to inhibit the transport of neutral amino
actively absorbed by a Na + dependent acids 60· 61 prompting the suggestion that
process 54 that is distinct from the mecha- hexoses and amino acids may share a sin-
nism for neutral amino acids and operates gle carrier mechanism, 61 -63 a "polyfunc-
at about 10% of the rate of the neutral sys- tional" carrier 62 • 63 for which they must
tem. 55 Unlike the neutral mechanism, it compete. However, if intestinal cells are
appears capable of transporting very allowed to accumulate leucine, addition
slowly (10% of maximal) even in the ab- of galactose to the lumen does not produce
sence of Na+. an exit of leucine from the cell into the lu-
Proline, hydroxyproline, and glycine men; that is, "countertransport" does not
share a transport system that actively ab- occur 64 as would have been expected if a
sorbs them against a concentration differ- single bidirectional carrier were handling
ence56 and may not have an absolute re- both hexose and amino acid. Although the
quirement for Na+. exact mechanism of interaction of glucose
Glutamic and aspartic acid (the dicar- and amino acid is not known, it is likely that
boxylic amino acids) have recently been they are competing for the same, limited
shown to be transported by a carrier mech- source of energy. 65
anism that is partially Na + dependent. 57
Because these amino acids are rapidly re- Absorption of Unhydrolyzed Protein
moved by transamination by the intestine
It has been known for several years that
after uptake, it has not been possible to
the immature intestinal cell of the newborn
determine whether they are transported
animal continues to absorb intact proteins
against a cell to lumen concentration gra-
for several weeks after birth. 66 This process
dient, but, considering the similarity to
may assist the animal in assimilating mater-
the neutral and basic mechanisms, active
nal globulins in milk and has been assumed
transport probably occurs. As noted above,
to occur by a passive mechanism. However,
the imino and dicarboxylic transport sys-
recent work in vitro has demonstrated that
tems may not be of physiological import-
methionine in the medium greatly reduces
ance since small peptides containing these
the capacity of everted intestinal sacs from
amino acids are absorbed intact. newborn piglets to absorb lactoglobulin. 67
Furthermore, uptake of -y-globulin re-
Stimulation of Lysine Transport quires oxygen and Na + and is reversibly
by Leucine inhibited by metabolic antagonists. 68
Leucine has recently been shown to aug- Thus, as more information unfolds, it ap-
ment the transport of lysine and arginine pears that even the absorption of unhy-
across the intestinal cell. 58 · 59 This finding drolyzed globulins in the newborn may be
is surprising since the basic and neutral · a complex and specific process.
amino acid transport systems are known to
be distinct from one another. The inter- The Future
action appears to somehow augment the The relative importance of brush border
efflux of lysine from the serosal side of the and intracellular oligopeptidases in pro-
intestinal cell by a mechanism that is not tein assimilation has not yet been precisely
yet understood. 59 Such a special interre- defined and will depend heavily upon thor-
lationship of the neutral and basic amino ough study of the specificity of the individ-
acids may serve a facilitating role during ual purified enzymes. Such information can
protein absorption (fig. 4) . then be correlated with in vivo physiologi-
542 PROGRESS IN GASTROENTEROLOGY Vol. 61 , No. 4, Part 1

cal experiments on the fate and interaction 8. Nordstrom C, Dahlqvist A: The cellular localiza-
of small peptides and amino acids during tion of enterokinase. Biochim Biophys Acta 198:
digestion and transport. 621-622, 1970
9. Jacobsen CF, Leonis J: A recording auto-titra-
Summary tion. Compt Rend Trav Lab Carlsberg, Ser Chim
27:333-339, 1951
1. The initial stage of digestion of die- 10. Dreyer WJ, Neurath H: The activation of chymo-
tary protein is accomplished by sequential trypsinogen. J Bioi Chern 217:527-539, 1955
action of activated pancreatic proteases 11. Keller PJ, Cohen E, Neurath H: Procarboxypep-
within the intestinal lumen, yielding about tidase. II. Chromatographic isolation, further
30% neutral and basic amino acids and 70% characterization, and activation. J Bioi Chern
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2. The amino acids are transported by 12. Cox DJ, Wintersberger E, Neurath H : Bovine
pancreatic procarboxypeptidase B. II. Mechanism
their specific mechanisms. The oligopep-
of activation. Biochemistry (Wash) 1:1078-1082,
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surface (particularly peptides containing the phenylalanyl chain of insulin. 2. The investiga-
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