Arginine: An Essential Amino Acid for the Cat

JAMES G. MORRIS ANDQUINTON R. ROGERS

Departments of Animal Science and Physiological
Sciences, University of California, Davis, California 95616

ABSTRACT The essentiality of arginine for the near-adult cat was

demonstrated in three preliminary and two main experiments. In the pre
liminary experiments, changing cats (body weights all in excess of 1.6 kg)
from a purified diet containing a complete amino acid mixture (basal) to

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a similar isonitrogenous diet without arginine ( —Arg) caused rapid loss of
body weight ( mean ±SE93.3 ±6.8 g in the first 24 hours ), emesis, and in-
appetance. In the main experiments the mean ±SE body weight of the cats
was 2.6 ±0.4 kg. When eight of these cats were given the —Argdiet after
an overnight fast, they all exhibited emesis, had tetanic spasms, and one
died. Other symptoms included hypersalivation, depression which in some
cases was followed by hyperesthesia, hyperactivity, ataxia, and dyspnea.
The plasma of these cats showed hyperammonemia and hyperglycemia
indicating that the clinical condition was caused by acute ammonia intoxi
cation. The eight cats given the comparable diet with arginine showed no
ill effects. Five cats given the basal diet with ornithine replacing arginine
on an equimolar basis showed neither an increase in plasma ammonia nor
glucose concentrations. Cats given the —Argdiet had extremely low 120
minute post-prandial levels of plasma free arginine (less than one-quarter
of the prefceding level ). It was concluded that the cat lacks the ability to
synthesize ornithine. The consequence of this metabolic deficiency in the
cat is that arginine is an essential nutrient: it provides a unique example
of a nutrient so critical that one meal without dietary arginine may result
in death. The —Argdiet supported growth in young rats, albeit at a slower
rate than rats fed the basal diet. J. Nutr. 108: 1944-1953, 1978.
INDEXING KEY WORDS arginine •ornithine •hyperammonemia
•cat nutrition •hepatic encephalopathy

Dietary arginine is required for either uricotelic animals, in contrast to adult

optimal growth or nitrogen balance of
young mammals including rats (1, 2),
guinea pigs (3), rabbits (4-7), swine (8),
and mink (9). However, it has been shown
that adult rats (10, 11), adult dogs (12),
children and adult man ( 13, 14 ), and post
pubertal and pregnant swine (15) are
capable of synthesizing adequate arginine
for maintenance or increase of nitrogen
balance. Therefore, it has been generally
assumed that dietary arginine is not re-
quired by adult mammals. As a result of
their lack of a functional urea cycle (16),
J J u u- J J LL
both growing and adult birds and other
1944
mammals, require dietary arginine,
In the course of a series of experiments
to determine the essentiality of amino acids
for the cat * the effect of deletion of argi-
nine from a purified diet was investigated,
An unexpected series of events followed
the deletion of arginine, which is reported
in the present paper. A communication on
one aspect of this study relative to the use
of &e cat as,a model, for hyperammonemia
in man has been P^Hshed' (17).
Recelvedfor publ,CationMays. ms.
'Rogers, Q. R. &Morris,j. G. (1978) Essentiai-
ity of amino acids for the growing kitten. J. Nutr.
(submitted).
 ARGININE DEFICIENCY IN THE CAT 1945

METHODS AND MATERIALS TABLE 2

Amino acid mixture used in the basal diet
Diets
Amino acid % of diet Amino acid % of diet
A purified basal diet (tables 1 and 2)
L-His-HCl-HiOL-IleL-LeuL-Lys-HClL-MetL-Cys-CysL-PheL-TyrL-ThrL-TrpL-ValL-Arg-HClL-Asn1.20'1.802.402.
which had been shown capable of support SerL
ing good growth rates ( mean ±SE, 17.3 ± ProGlyL-GluL-AlaNa-acetate<%

4.8 g gain/day) in weanling kittens was

used. For the arginine-free diet (—Arg),
an isonitrogenous amount of alanine re
placed the arginine in the basal diet. The totalAmino
of diet
increase in weight of amino acid required basesonlyProtein
acida
for this substitution was deducted from the equivalent*Nitrogen
carbohydrate components of the diet. For

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6.25Amino X
the arginine-free orni thine diet, ( —Arg ofcalories
acids as %
+Orn) orni thine replaced arginine on a basaldiet1.002.002.006.001.002.5034.7%31.1%28.0%27.2%23.0%
in
equimolar basis.

Animais
Cats. Conventional short hair cats which
had been vaccinated with panleukopenia
vaccine,3 treated with the anthelmintic
piperazine, and accustomed to the puri
fied basal diet were used as experimental
animals. Their body weights were all in
excess of 1.6 kg, and they were individually
housed in stainless-steel cages either 0.6 X
0.6 X 0.9 m high or 0.6 X 0.5 X 0.8 m high.
Rats. Twelve male albino rats of the
Sprague-Dawley strain mean ( ±SE) body
weight of 55.4 ±0.4 g were individually
housed in screened bottom cages in a light
TABLE l
Composition of the basal semi-
purified amino acid diet
Dietary component % of diet
mixture1Turkey
Amino acid
fat!Starch3Sucrose*Salt
mixture*Vitamins'Choline
chloride34.725.019.2715.74.01.00.33
Total 100.00
1See table 2 for composition. 2Heat rendered
by cooking in large open pans +0.02% BHT.
' Pearl Starch (raw cornstarch) A. E. Staley Mfg.
Co., Decatur, Illinois. 4 California and Hawaii
Sugar Co., San Francisco. 6Hegsted's Salt Mixture
IV (38). «Reference (18) plus biotin, folie acid,
and vitamin Biz, see reference (19) for complete
composition of vitamin mixture.
'0.98 free base. '2.26 free base. >1.66 free base.
4 Added to balance the bydrochlorides. ••
Weight of amino
acids less 1 mole of water per mole of amino acid.
controlled (12 hour-12 hour light-dark
ness) room at 28 ±2°.
Design
Three preliminary dietary crossover ex
periments A, B, and C were conducted
with six cats given the basal and the —Arg
diets. In the first two experiments, the same
three cats were used ( mean ±SE body
weight, 1.9 ±0.2 kg), whereas in the third
experiment a different group of three cats
( mean ±SE body weight, 2.0 ±0.2 kg )
were fed the diets. In experiment A, the
—Argdiet was given to the cats for 2 days,
whereas in B and C it was fed for up to 5
days. The dietary changes from basal to
—Argand reverse did not involve an inter
mediate period of food withdrawal. Daily
food intake and body weight changes were
measured as well as observations on the
behavior of the animals.
The objective of experiment D, was to
measure some of the metabolic alterations
which occurred in cats following ingestión
of a single meal of the —Argdiet. For this
experiment, 16 near-adult cats ( mean ±SE
body weight, 2.59 ±0.36 kg) were fasted
from 1700 hours the previous afternoon.
At 0800 hours eight of the cats were ran-
2 Morris, J. G. & Rogers, Q. R. (1976) Arginine:
an essential amino acid for the adult cat. J. Nutr.
106 (7),xxxll.
»Feloclne® ; Norden Laboratories, Lincoln, Ne
braska.
1946 JAMES G. MORRIS AND QUINTON
L R-i'ftvM
li B*5*1-
ii':tTAHC \]
Fig. l Body weight changes ( mean ±SE) of
three cats given the basal and —Argdiets in ex
periments A, B, and C. Cross hatched areas indi
cate periods when the —Argdiet was given, arrow
indicates change in diet. In experiment B one cat
was taken off the —Arg diet after 3 days while
the other two cats continued receiving the diet
for the full 5 day period.
domly assigned to the basal diet and eight
assigned to the —Argdiet. The food bowls
were removed 45 minutes after presenta
tion of the diets and the food intakes mea
sured. Heparinized samples of jugular
blood (4 ml) were taken before the diets
were given (0 time), and again at 45, 120,
and 300 minutes after the diets were first
given to the cats.
The objective of experiment E was to
determine if ornithine would prevent the
metabolic disturbances associated with the
—Argdiet. This experiment, followed ex
periment D by 11 days and used five of the
seven surviving cats which previously re
ceived the —Arg diet, plus two others
which previously had readily eaten the
basal diet in the 45 minute period. The five
cats previously assigned to the —Argdiet
were given the —Arg+Orn diet, whereas
the two which previously received the
basal diet were given the —Arg diet.
Heparinized samples of blood ( 4 ml ) were
removed at 0, 45, 90, 120, 210, and 300
minutes after presentation of the diet.
In experiment F, a double crossover de
sign was used to evaluate the comparative
food intake and body weight gain of young
rats given either the basal or the —Arg
R. ROGERS
diets ad libitum. Twelve rats were ran
domly assigned to two groups each of six
animals. Both groups received the basal
diet for 7 days, which was followed by one
14-day and one 20-day crossover period.
Methods
Plasma free amino acids were measured
by an automatic amino acid analyzer *
using a single column, lithium buffer sys
tem. Blood samples were kept on ice until
the plasma was separated by centrifuga-
tion. The plasma was stored at —20° until
the proteins were removed by sulfosalicylic
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BASAL acid ( final concentration, 3% ) and the
supernatants analyzed.
Plasma ammonia was measured by an
enzymatic coupled method involving the
oxidation of NADH with a-ketoglutarate.5
Glucose in plasma was measured by the
O-toluidine method (20) adapted for auto
mated analysis.8
RESULTS
Experiments A, B, and C
In experiment A, within 24 hours of the
cats being fed the —Argdiet there was a
marked loss in body weight accompanied
by aphagia in two cats, and lethargy (fig.
1). As this reaction was atypical of any
known simple amino acid deficiency, two
further experiments B and C were done to
eliminate the possibility of the condition
being caused by a dietary contaminant.
A fresh diet was prepared for experiment
B using a different source of all ingredients
other than the amino acid mixture. Again
cats given the —Argdiet showed similar
symptoms as those in experiment A. In ad
dition, two of the cats given the —Argdiet
had vomitus in their cages and one of these
cats could barely stand unaided. Blood
samples were taken on the fifth day from
cats given both the —Argand basal diets,
were pooled accordingly to treatments, and
the pooled samples were analyzed for
plasma free amino acids and for a clinical
profile.7 The amino acid pattern in the
«Beckman Model 121 M Amino Acid Analyzer.
5Eskalab Ammonia Reagent Kit Catalog No. 82363.
Smith-Kline Instruments Inc.
•
Auto Analyzer, Technlcon Instrument Corp..
Tarrytown.
' SMA/12. New York.
Transaminaaes-glutamic-pyruvlc and glu-
tamlc-oxalacetlc, lactic dehydrogenase, alkaline phos-
phatase, bllirubin, blood urea nitrogen, glucose, cho
lesterol, Inorganic phosphate, calcium, albumin, and
total protein.
 ARGININE DEFICIENCY IN THE CAT
—Arg cats showed the anticipated lower
levels of free arginine and ornithine than
cats given the control basal diet or a fish
based dry cat food." However, the levels
of ammonia and glutamine were compara
ble to cats given either the control or com
mercial diets. These results did not support
our first hypothesis that a deficiency of
arginine had an adverse effect on the cats
due to its role in the urea cycle. From the
clinical profile no abnormalities were ap
parent other than hyperglycemia in the
—Argcats (257 mg glucose/dl compared
to a value of 98 mg/dl in the cats receiving
the control diet).
For experiment C, an entirely fresh
batch of the —Argdiet ( using a new amino
acid mixture) was prepared. Again, the
clinical picture was similar to that ob
served in experiments A and B. In addition,
two of the cats when changed to the basal
diet after having had the —Argdiet for 5
days, ate only 1 and 2 g, respectively, of
the basal diet during the first 24-hour pe
riod. In the second 24-hour period these
two cats were each offered two food bowls,
one of the basal diet alone, and one of the
basal diet plus onion and garlic powder.
The consumption of the basal diet alone
continued to be very low: 3 and 9 g for the
second 24-hour period. However, the con
sumption of the basal plus garlic and onion
powder diet was 23 and 32 g, respectively,
over this second period and 69 and 87 g,
respectively, over the third 24-hour period.
Thus, it appears that cats develop a strong
learned aversion to the —Argdiet as a re
sult of the nausea and emesis which fol
lows its consumption. In all three pre
liminary experiments (A, B, and C) cats
given the —Argdiet showed a consistent
TABLE 3
Ammonia concentration of the plasma from fasted cats
fed a single meal of the basal or
—Argdiet (experiment D)
Time (minutes)
Diet 0 45 120
M/di
Basal 174±18 169±16 135±7 129 ±12 lowed by prostration and dyspnea often
-Arg 156±18 344±45 1,396±92 335*±91 accompanied by tetanic spasms with em-
Mean±sE, n = 8 except where indicated by *,
n = 7.
1947
TABLE 4
Glucose concentration of the plasma from fasted cats
fed a single meal of basal or
—Argdiet (experiment D)
(minutes)45
DietBasal 120mg/dl84
±2.0 96±1.7 1.5
-Arg090±1.9
89±2.8Time
86±1.9 242±29.530088±
271±45.4
Mean±SE,n = 8.
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loss of body weight in the first 24 hours
(mean ±SE, 93.3 ±6.8 g, n = 9) which
continued as long as the —Arg diet was
fed (fig. 1); a marked depression of food
intake (mean ±SE,22 ±4% of that of the
previous day's intake when given the basal
diet, n = 9), emesis and in two cases diar
rhea, hemoconcentration, and inability to
stand unaided.
Experiment D
In experiment D, the mean ±SEfood in
take of the cats given the —Argand basal
diets in the 45 minute period was 7.4 ±
0.68 g range 5 to 11 g and 6.6 ±0.73 range
4 to 9 g, respectively. These intakes were
not significantly different. No obvious clin
ical symptoms were apparent in the cats
receiving either diet at the 45 minute sam
pling when the food was removed. How
ever, by 2 hours, emesis had occurred in all
cats receiving the —Arg diet; mean ±SE
time of emesis 82 ±3.5 minutes after first
presentation of the —Argdiet. No adverse
symptoms occurred at any time in the cats
receiving the basal diet. Emesis was ac
companied by hypersalivation and frothing
from the mouth. Cats initially showed de
pression, which was frequently accom
panied by closure of the eyes, nodding of
the head in the vertical plane and rapid
small amplitude twitching of the ears.
Later some cats exhibited hyperesthesia,
300
hyperactivity, as evidenced by sudden un
controlled running around in the cage and
ataxia. Hyperactivity was generally fol
8 Friskles Ocean Fish, Carnation Company, Los
Angeles.
1948 JAMES G. MORRIS AND QUINTON R. ROGERS

120 IM
MINUTES

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9

Ã-

l.

120 180 120 1*0

MINUTES MINUTES

Fig. 2 Plasma concentrations of free arginine, (A); citrulline, (B); and omithine, (C);
and the branched chain (valine plus leucine plus isoleucine) to phenylalanine plus tyrosine
ratio (BCAA/phe + tyr ) (D) of pooled plasma from cats given the basal O O, —
Argi>
Õexperiment D), • •;—Args(experiment E), A A and the —Arg+ Om, A A
iets.

prosthotonus and extended limbs with ex A marked and sustained hyperglycemia

posed claws. Apnea occurred during
tetanic spasm which resulted in cyanosis
and death of one cat of 2.7 kg body weight
which ate only 8 g of the diet. This cat
also vomited so the total weight of amino
acid mixture absorbed was undoubtedly
less than 2.5 g. On necropsy, the brain of
this cat had disseminated foci of acute
hemorrhage in the medulla oblongata,
mesencephalon and thalamus. No other
significant lesions were found.
The ammonia concentration of the
plasma of cats given the basal and —Arg
diets in respect to the sampling times is
shown in table 3. Ammonia concentration
of the plasma from cats receiving the basal
diet snowed no significant change with
time. However, the concentration in the
plasma of cats receiving the —Arg diet
more than doubled in the first 45 minutes
and by 120 minutes had attained a mean
level of 1,396 Mg/dl.
developed in cats receiving the —Argdiet
between 120 and 300 minutes (table 4)
whereas cats given the basal diet showed
only small fluctuations with time in plasma
glucose concentration.
Plasma concentrations of the free amino
acids arginine, ornithine, citrulline, and the
branched chain amino acids (valine, leu-
cine, plus isoleucine) to phenylalanine plus
tyrosine ratio (BCAA/phe 4- try) of pooled
plasma of cats given the —Argand basal
diets are presented in fig. 2. There was a
markedly lower post-prandial concentra
tion of arginine and the other urea cycle
intermediates, citrulline, and ornithine, in
the plasma of the —Argcats than in those
receiving the basal diet
Experiment E
Cats given the —Arg+Orn diet showed
no adverse clinical symptoms. Plasma con
centrations of ammonia and glucose were
 ARGININE DEFICIENCY IN THE CAT 1949
TABLE 5
Ammonia concentration of plasma from fasted cats fed a single meal
of the —Argor —Arg-\-Orn diet (experiment E)

(minutes)Diet-Arg Time

238 580 408 83

-Arg +Ornn1» 50918545311 154±1690eg/at1,085
141±201501,337
129±44210969
179±453001369593
±25
1Mean±8E. »
Cat number 56. ' Cat number 62.

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not elevated (tables 5 and 6) and were
similar to those found in cats given the
basal diet in experiment D. Of the two
cats given the —Argdiet one cat (number
56) had a severe and sustained hyper-
ammonemia while the other cat (number
62) had only a mild and transient eleva
tion of ammonia which reflected the small
amount of diet eaten, (3.5 vs. 6 g). Hyper-
glycemia developed in cat 56 which had
the severe hyperammonemia, whereas all
cats given the —Arg+Orn diet maintained
normal levels of plasma glucose.
The post-prandial free arginine, orni-
thine, citrulline, and BCAA/phe + tyr con
centrations of plasma from cats given the
basal, —Arg and -Arg +Orn diets are
presented in fig. 2. The —Arg + Orn diet
resulted in a marked, but transient, eleva
tion of plasma ornithine which declined to
below the basal dietary level at the 150
minute and subsequent samplings. This
diet maintained plasma citrulline, at levels
similar to the basal diet, but did not cause
a post-prandial rise in plasma arginine. The
regression of plasma glucose concentra
tion (y, mg/dl) on plasma ammonia con
centration (x, ¿ug/dl)from the 120 or 150
minute sampling of all cats in experiments
D and E gave the following relationship:
y = 74.9 + 0.125x, with a correlation co
efficient of 0.8 (P<0.01).
Experiment F
The growth rate and feed intake of rats
given the —Argdiet was significantly less
( P < 0.01 ) than those receiving the basal
diet. The growth rate of rats in the first
period was basal, 5.2 ±0.15 g/day and
—Arg,1.6 ±0.13 g/day, and in the second
period basal 5.05 ±0.24 and -Arg, 0.63 ±
0.41. Corresponding daily mean ±SE feed
intakes were: first period—basal, 10.6 g;
—Arg,7.4 g; second period—basal, 12.1 g;
-Arg, 9.1 g.
DISCUSSION
The time course for the development of
clinical symptoms associated with a de
ficiency of an essential dietary component
is usually of the order of at least days, and
more generally of the order of weeks.
Amino acid deficiencies of animals pre
viously fed a low protein diet may result

TABLE 6
Gigueóse
concentration of the plasma from fasted cats fed a single meal of
—Argor —Arg-\-Orn diel (experiment E)

(minutes)90
Diet-Arg 150mg/dl122

291
1»5095 84 88 80 98 95 104
-Arg +Ornn1' 94±1'459588 ±2Time87±3 96±1210309
93 ±5300195
93 ±3
'Mean±SE. «
Cat number 56. »
Cat number 62.
1950 JAMES G. MORRIS AND QUINTON
in a depression of food intake and weight
gains within a few hours, but no other
early adverse effects have been reported.
Arginine deficiency in the cat represents a
unique example of an essential dietary
component which if lacking, causes severe
adverse effects and is life-threatening. The
consumption by the near-adult cat of a
single meal containing amino acids devoid
of arginine may lead to serious clinical
symptoms or even death within several
hours from acute ammonia intoxication.
We know of no other essential dietary
component whose deficiency has such
acute, drastic effects upon the animal.
The diagnosis of acute ammonia intoxi
cation is consistent with the hyperam-
monemia, hyperglycemia, and clinical
symptoms found in the cats given the
—Argdiet in experiments D and E. The
mean plasma ammonia concentration of
cats given the basal diet remained below
200 /tg/dl at all times, whereas those re
ceiving the —Arg diet had mean plasma
concentrations nearly seven times this level.
Hyperglycemia has been reported follow
ing experimentally induced ammonia in
toxication (21-23) and is resistant to in
sulin (22). The mode of action of am
monia in producing hyperglycemia is
apparently through release of glucagon.9
Evidence supporting the role of ammonia
in the production of hyperglycemia in the
cat is the positive correlation (0.8) we
found between these variables, and a sim
ilar positive correlation (0.84) between
blood ammonia and glucose concentrations
which has been reported in rats following
induction of hyperammonemia by paren-
teral urease (23). Hyperglycemia has also
been reported in humans associated with
congenital hyperammonemia (24). Clini
cal symptoms of ammonia intoxication in
the cat are similar to those reported in rats
and pigs following injection of ammonium
salts (25, 21) or in sheep due to injection
of ammonium salts or ingestion of urea
(26) or rats following injection of massive
doses of amino acids (27). The greater
severity of symptoms expressed by cats in
experiments D and E than those in the
preliminary experiments A to C is no doubt
a result of the different experimental pro
tocol used. In the preliminary experiments,
R. ROGERS
cats were changed from the basal to the
—Argdiet without a period of feed with
drawal. However, for experiments D and
E the cats were prefed the basal diet for
several days and fasted overnight which
would have depleted their circulating
levels and presumably also hepatic levels
of arginine. The ingestion of the —Arg
diet containing carbohydrates, fat, and
amino acids would suppress mobilization
of tissue protein as a source of energy and
of arginine, but would not suppress the
catabolism of the absorbed amino acids.
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Cats normally exhibit a high rate of amino
acid catabolism as evidenced both by their
high requirement of protein for mainte
nance (28-30) which is about 16 to 19%
of the calories for the adult cat, com
pared to only about 4% for the adult dog
(31-33) and by their apparent inability to
regulate the activities of enzymes con
cerned with the degradation of some amino
acids and the urea cycle (34). Therefore,
the free amino acids ingested in the —Arg
diet would be rapidly absorbed and catab-
olized and result in an ammonia overload
to the cat. Overnight fasting apparently
causes severe depletion of urea cycle inter
mediates in the liver. When the cats were
subjected to an ammonia load from de-
aminated amino acids the rate of conver
sion of ammonia to urea was less than the
rate of ammonia production, thus causing
hyperammonemia and acute ammonia in
toxication. The reasons for ammonia intoxi
cation not occurring when cats are given a
protein (nitrogen) free diet or starved is
that there is no ammonia load to excrete
in the former physiological state and in the
latter arginine is made available from
mobilization of tissue proteins.
Since ornithine completely protected the
cats from hyperammonemia in the ab
sence of dietary arginine (experiment E)
it would appear that the cats susceptibility
to ammonia intoxication is a result of its
inability to synthesize ornithine. As other
mammals, e.g., adult rats (10, 11), dog
(12), and man (14) can maintain nitrogen
balance or even grow in the absence of
dietary arginine, it is evident that they
are capable of ornithine synthesis. Rats in
•
Strombeck, D. R., Rogers, Q. R. & Stern, J.
(1978) (Unpublished work).
 ARGININE DEFICIENCY IN THE CAT
experiment F, given the same —Argdiet
as given to the cats, grew although at a
slower rate than that found after giving
the basal diet, indicating ornithine synthe
sis was possible in rats fed this identical
diet. It should also be noted that the
amino acid mixture in the diet contained
both proline and glutamic acid which spare
dietary arginine in the rat (35) and pro-
line has been shown to be used in animal
tissues as a precursor for ornithine synthe
sis (36).
The amino acid profile of cats given the
—Argdiets (fig. 2) showed very low 120
minute post-prandial levels of arginine
accompanied by ornithine and citrulline
levels of about half the prefeeding levels.
These cats also had lower concentrations
of plasma urea at 120 and 300 minutes than
cats given the basal diet. While this dif
ference in plasma urea could indicate
differential synthesis, there was also a dif
ference in the amino acid load absorbed in
favor of cats consuming the basal diet.
Cats receiving the —Arg +Orn diet
showed a rapid ( 14-fold ) post-prandial rise
in plasma free ornithine, which was then
rapidly depleted to almost pre-prandial
levels by 210 minutes. This depletion of
ornithine was accompanied by a fall in
plasma-free arginine and only a small rise
in citrulline. Thus, it appears that while
dietary ornithine can fulfill an anaplerotic
role in the urea cycle, it may not be able
to sustain normal levels of circulating
arginine.
The same —Argdiet which resulted in
extensive body weight loss in cats, sup
ported growth (experiment F) in rats,
albeit at a much slower rate than the basal
(+Arg) diet (+Arg, 5.2; -Arg, 1.6 g/day
in the first crossover and +Arg, 5.1; —Arg,
0.6 g/day in the second crossover). The
differential performance of rats given these
diets was much greater than that recorded
by Rose and co-workers ( 1) when estab
lishing the essentiality of arginine for
growth in the rat. Their results in one
study were, +Arg, 1.65; —Arg,1.35 g/day
( n = 102 and 108, respectively ) and in an
other study, 4-Arg, 1.29; -Arg, 1.03 g/day
(n = 50 and 48, respectively). At least
part of the difference was probably at
tributable to inadequacies of vitamins and
1951
minerals in Rose's diets which prevented
full expression of the growth potential of
the +Arg diet. Rose's diets contained a
high percentage of fat (30%) comparable
to our diet. For a diet lower in lipids (10%
corn oil), Milner et al. (2) reported growth
rates of +Arg, 3.59; —Arg,1.35 g/day for
rats of 30 to 35 g initial body weights: and
for rats of 150 to 175 g initial body weights,
+Arg, 5; -Arg, 4 g/day. The diet they
used, like that of Rose's, had a lower level
of amino acids (14%) than ours (31%
amino acids, table 2) and hence less of a
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load on the urea cycle to excrete nitrogen
and possibly a lower requirement for argi
nine. Similar results have been reported
by Wang et al. (37) for the growth rate of
rats given a diet containing 21% amino
acids and 10% corn oil ( +Arg, 2.40; —Arg,
1.25 g/day).
The molar ratio of the sum of the free
branched chain amino acids (BCAA), i.e.,
valine, plus leucine plus isoleucine, to
phenylalanine plus tyrosine in the plasma
of cats given the basal or the —Arg+Orn
diets increased immediately after ingestion
of food to levels in excess of 3.5, then
slowly declined to approximately prefeed
ing levels of 2.5 to 2.6. At all times, the
ratio exceeded 2.4. In contrast, in the two
groups of cats given the —Arg diet, the
BCAA/phe + tyr ratio showed the same
rise after feeding but then rapidly de
clined to levels as low as 1.6 which was
followed by a slow rise to approximately
prefeeding levels. A low ratio of BCAA/
phe + tyr of 1.0 to 1.5 has been shown to
be associated with hepatic encephalopathy
in dogs (39) and in human patients (40).
Normalization of this ratio to 3.0 to 3.5 by
intravenous infusions of amino acid mix
tures high in BCAA and low in aromatics
reverses hepatic encephalopathy in both
species (39, 40). In man, hepatic encepha-
lopathies of differing etiologies result in
similar depressions of the BCAA/phe + tyr
ratio (41). Soeters and Fischer (42) have
hypothesized that the changes in the amino
acid patterns may be the cause of the
hepatic encephalopathy. It would therefore
appear that the cat may be a useful animal
model for not only investigating hyperam-
monemia (17) but also hepatic encepha
lopathy.
1952 JAMES G. MORRIS AND QUINTON
ACKNOWLEDGMENTS
This research was supported in part by
a gift from the Carnation Company, Los
Angeles and in part by funds provided
through a National Institutes of Health,
Public Health Services Biomédical Re
search Support Grant No. 5S01RR05457.
We thank Dr. J. J. Kaneko and Ms. R. Mills
for the measurements of plasma ammonia,
Mr. John Bryan for plasma glucose analy
ses, Dr. S. Larsen for the pathology report,
and Mr. Arthur Aguirre and Ms. Jane
Bishop for technical assistance.
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