1000
Asia Pacific J Clin Nutr (1997) 6(2): 88-91
Asia Pacific J Clin Nutr (1997) 6(2): 88-91
Peptide
digestion and absorption in humans:
portal vein, hepatic vein, and peripheral venous amino
acid concentrations
M Yamakawa1 MD, J Maeda1 MD, K Sugisaki1 MD, T Fujita1 MD, T Oohara1 MD, H Hara2 PhD and S Mitani3 MD
1 Third Department
of Surgery, Faculty of Medicine, University of Tokyo, Tokyo
2 Department of Agriculture, University of
Hokkaido, Sapporo City
3 Yamato Tokushukai Hospital, Yamato City,
Japan
An oligopeptide preparation and an amino acid mixture
with an identical composition were administered intraduodenally
to a patient with a catheter in the portal vein, and blood samples
were collected over time from the portal vein, the hepatic vein,
and a peripheral vein to investigate amino acid digestion and absorption.
When the oligopeptide preparation was administered,
amino acids appeared rapidly in the portal blood and monomodal well-balanced
absorption curves were obtained. When the amino acid mixture was
given, however, amino acid levels in the portal blood indicated
a bimodal pattern of absorption. Evaluation of the kinetics of various
amino acids after administration of the two preparations showed
that they could be classified into the following four groups: 1)
amino acids showing hepatic uptake (threonine, methionine, phenylalanine,
lysine, histidine, arginine, serine, and proline), 2) amino acids
released from peripheral tissues and taken up by the liver (alanine,
glutamine, and glycine), 3) amino acids not showing hepatic uptake
(leucine, valine, and isoleucine), and one amino acid released from
the liver for peripheral uptake (glutamic acid).
These findings suggest that the nature of the protein
source and the kinetics of individual amino acids should be taken
into account in nutritional therapy and nutritional assessment.
Key words: Oligopeptides, amino
acids, digestion absorption, human, portal vein, hepatic vein, peripheral
vein, hepatic uptake, peripheral release, peripheral uptake, BCAA,
enteral nutrition
Introduction
Disturbances of digestion and absorption develop after
surgery as well as in the short-bowel syndrome and with inflammatory
bowel disease. For patients with such conditions, amino acid mixtures
have been used successfully as a nitrogen source that can be rapidly
digested and absorbed. According to Matthews et al1,
and Silk et al2, some 1000 ingested protein is degraded
to amino acids, but a considerable portion is absorbed in the form
of dipeptides or tripeptides (oligopeptides), with the absorption
rate of the latter being higher.
To investigate the behaviour of oligopeptides and
amino acids as nitrogen sources, portal vein, hepatic vein, and peripheral
venous amino acid concentrations were measured in a human subject
after administration of an oligopeptide preparation and an amino acid
mixture. The kinetics of various amino acids were also investigated.
Patient and
methods
The patient was a 45-year-old man who had a catheter
inserted into the portal vein at the time of subtotal gastrectomy
for pyloric stenosis secondary to duodenal ulcer. The catheter was
intended for insulin infusion for the treatment of chronic active
hepatitis. The patient showed GOT and GPT levels over 200 IU/l preoperatively,
and received a drip infusion containing regular insulin (40 units/day)
and glucose (200g/day) through the catheter for 70 days postoperatively.
Serum GOT level and GPT levels fell to less than 70 IU/l, 60 IU/l
respectively after this therapy. The patient fully recovered from
the operative stress, and no medication or therapy were necessary
except the insulin therapy. A catheter for right hepatic vein angiography
was inserted via the right long saphenous vein 85 days postoperatively
to evaluate what ongoing pathological change accompanied his chronic
hepatitis and was left in situ.
After an overnight fast, 15 g of an oligopeptide preparation
(egg albumen hydrolysate containing >70% dipeptides and tripeptides:
Terumo Inc, Tokyo Japan) was dissolved in 100 ml of lukewarm water
and administered via a nasoduodenal tube over 1 minute. Table 1 shows
the amino acid composition of the oligo-peptide preparation. Three
days after the study, a mixture of amino acids (Terumo Inc, Tokyo,
Japan) with an identical composition to the oligopeptide preparation
was administered in a similar fashion. The patient was stable in the
interval between these studies. Blood samples were collected from
the portal vein, the hepatic vein, and the left cubital vein at the
start (0 min) of administration as well as 10, 20, 30, 60, 90, and
120 min after administration (total blood volume: 63 ml). Plasma amino
acid concentrations were measured using an amino acid analyser (HITACHI
835: HITACHI Co Ltd, Hitachi-city, Japan) after separation of amino
acids and peptides using the copper complex-DEAE Sephadex technique.
The study protocol was approved by the hospital ethics committee,
and informed consent was obtained from the patient.
Table 1. Amino acid composition of the oligopeptide
preparation.
| Amino acid |
g/ 100g
|
| Aspartate |
4.92
|
| Threonine |
4.58
|
| Serine |
6.85
|
| Glutamate |
8.23
|
1000
| Glycine |
3.40
|
| Alanine |
5.95
|
| Cysteine |
2.30
|
| Valine |
6.62
|
| Methionine |
4.81
|
| Isoleucine |
4.88
|
| Leucine |
7.13
|
| Tyrosine |
3.92
|
| Phenylalanine |
5.70
|
| Lysine |
7.12
|
| Histidine |
2.42
|
| Tryptophan |
1.15
|
| Arginine |
5.97
|
| Proline |
3.66
|
| Asparagine |
4.93
|
| Glutamine |
5.40
|
| Total |
100.00 (wt%)
|
Results
Absorption
of the oligopeptides and amino acid preparations:
Figures 1-4 show amino acid concentrations in the
portal vein, hepatic vein, and peripheral vein. When the oligopeptide
preparation was administered, the levels of all amino acids showed
a sharp rise in the portal vein with a peak at 30 min after administration.
No oligopeptides were 1000 detected in portal, hepatic, or peripheral
venous blood.
When the amino acid monomer mixture was administered,
some amino acids showed rapid absorption, but others showed more gradual
absorption and lower peak levels. A bimodal absorption pattern was
also observed with some amino acids. The amino acids could be divided
into the following 4 groups on the basis of differences in their portal,
hepatic, and peripheral venous concentrations.
1) Amino acids showing hepatic
uptake (Fig. 1). Threonine, methionine,
and phenylalanine showed a positive concentration difference between
the portal and hepatic veins after administration of both the oligopeptide
and amino acid monomer preparations, and the magnitude of the difference
increased with time, suggesting active hepatic uptake. Similar findings
were obtained for lysine, histidine, arginine, serine, and proline
(data not shown).
2) Amino acids released peripherally
with subsequent hepatic uptake (Fig. 2). Alanine and glutamine showed a negative concentration
difference between the hepatic and peripheral veins, suggesting release
from the peripheral tissues (probably from the muscles). The difference
between the portal and hepatic veins was positive, indicating hepatic
uptake of the released amino acids. Similar findings were obtained
for glycine (data not shown).
3) Amino acids without hepatic
uptake (Fig. 3). Leucine, valine, and
isoleucine exhibited a positive concentration difference between the
portal and hepatic veins after oligopeptide and amino acid monomer
administration, but the differences were small, suggesting that hepatic
uptake was slight.
4) An amino acid released from
the liver and metabolised peripherally (Fig. 4). Glutamic acid showed a large negative concentration difference
between the portal and hepatic veins, suggesting release from the
liver. In addition, the concentration difference between the hepatic
and peripheral veins was positive, indicating that glutamic acid was
taken up by the peripheral tissues.
Figure 1. Kinetics of amino acids undergoing
hepatic uptake.
Figure 2. Kinetics of amino acids released
from the peripheral tissues with subsequent hepatic uptake.
Figure 3. Kinetics of amino acids not undergoing
hepatic uptake.
Figure 4. Kinetics of glutamic acid.
Discussion
Digestion and absorption of oligopeptides has been
suggested to be more physiologic than that of amino acids1,2.
In the present study, oligopeptide administration generally produced
absorption curves with a sharp peak, and blood levels returned to
the pre-administration baseline after 90-120 min, indicating rapid
and well-balanced digestion and absorption.
After administration of the amino acid mixture, however,
bimodal absorption curves were generally observed. This may have been
because there was competition for absorption between various amino
acids, or because the extent of absorption of the amino acids varied
between different parts of the small intestine and absorption occurred
throughout the small bowel. In contrast, oligopeptide preparations
have been reported to be absorbed in th 1000 e proximal small intestine
(mainly the jejunum), suggesting their usefulness in patients with
short-bowel syndrome and inflammatory bowel disease3, and
our findings in the present study supported these previous observations.
We also investigated the kinetics of various amino
acids after absorption. Threonine, methionine, phenylalanine, lysine,
histidine, arginine, serine, and proline showed large concentration
differences between the portal and hepatic veins, indicating uptake
by the liver. Alanine and glutamine showed similar concentrations
in the portal and hepatic veins, but showed a large negative concentration
difference between the hepatic and peripheral veins, suggesting release
from the peripheral tissues. It is worth noting that these amino acids
can transfer amino groups4.
The concentration difference between the portal and
hepatic veins was small for leucine, valine, and isoleucine, which
are branched-chain amino acids (BCAA), suggesting that they were taken
up by the liver in the minimum amounts necessary as essential amino
acids. The BCAA showed large concentration differences between the
hepatic and peripheral veins after administration of the oligopeptide
preparation, indicating peripheral tissue uptake. The patient had
a good appetite and gained body weight postoperatively, and was clinically
stable throughout. Therefore, we considered the patient to be unstressed.
BCAA uptake by peripheral tissues during stress has been studied previously5;
their kinetics appear to be similar in the absence of stress, on the
basis of our present findings. The BCAA concentration patterns were
somewhat different when the amino acid monomer mixture was administered,
suggesting that BCAA may have different kinetics when given as oligopeptides
and as amino acid monomers.
Unlike other amino acids, glutamic acid was clearly
released from the liver. This may have been due to the hepatic production
of glutamate by release of an amino group from glutamine4
or the supply of an amino group to a -ketoglutarate.
The methodology of on this study provides an indirect
way to demonstrate amino acid kinetics. Radiolabeling would enable
more direct study of kinetics and could distinguish between the fate
of administered amino acids and those derived from endogenous turnover.
Nevertheless, the concentration differences reflect amino acid kinetics,
in the liver of a patient who was not cirrhotic and where there were
no alterations of the hepatic venous bed. Although, we have only a
single data set in one patient, we consider the study valuable as
a human study.
In conclusion, when nutritional therapy is formulated
or nutritional assessment is made, it is important to take into account
the differing kinetics of various amino acids as well as differences
in digestion and absorption between oligopeptide and amino acid preparations.
References
- Matthews DM, Adibi SA. Peptide absorption. Gastroenterology
1976; 71:151-161.
- Silk DBA, Fairelough PD, Clark ML, Hegarty E, Marrs
TC, Addison JM, Burstion D, Clegg KM, Matthews DM. Use of a peptide
rather than free amino acids nitrogen source in chemically defined
"elemental" diet. JPEN 1980;4:548-553.
- Hosoda S, Shimoyama T, Takahashi T, Bamba T, Kitano
A, Matsueda K, Hiwatashi N. Nutritional management of Crohn’s
disease with a peptide-based enteral formula. Asia Pacific Journal
of Clinical Nutrition 1993; 2: 63-70.
- Linder MC. Nutrition and metabolism of proteins.
In: Linde 6b2 r MC, ed. Nutritional biochemistry and metabolism
with clinical applications. East Norwalk: Appleton & Lange,
1991:89-109.
- Freund H, Yoshimura N, Fisher JE. The role of the
branched chain amino acids in decreasing muscle catabolism in
vivo. Surgery 1978; 83: 611-618.
Peptide digestion
and absorption in humans: portal vein, hepatic vein, and peripheral
venous amino acid concentrations
M Yamakawa, J Maeda, K Sugisaki, T Fujita,
T Oohara, H Hara and S Mitani
Asia Pacific Journal of Clinical Nutrition (1997) Volume 6, Number
2: 88-91
Copyright © 1997 [Asia Pacific Journal of Clinical
Nutrition]. All rights reserved.
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