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Amino acid interactions in chicknutritionJ. P. F. D'mello a b
& D. Lewis aa Department of Applied Biochemistry and Nutrition,
University ofNottingham, School of Agriculture, Sutton Bonington,
Loughboroughb Department of Agricultural Biochemistry, The East of
ScotlandCollege of Agriculture, West Mains Road, Edinburgh,
9Published online: 08 Nov 2007.
To cite this article: J. P. F. D'mello & D. Lewis (1970)
Amino acid interactions in chick nutrition,British Poultry Science,
11:3, 299-311
To link to this article:
http://dx.doi.org/10.1080/00071667008415820
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Br. Poult. Sci., I I : 299-311. 1970 Oliver & Boyd: printed
in Great Britain
AMINO ACID INTERACTIONS IN CHICKNUTRITION
I. THE INTERRELATIONSHIP BETWEEN LYSINEAND ARGININE
J. P. F. D'MELLO1 AND D. LEWISDepartment of Applied Biochemistry
and Nutrition,
University of Nottingham, School of Agriculture, Sutton
Bonington, LoughboroughReceived for publication 13th October
1969
SYNOPSIS
A series of experiments has been conducted to investigate the
specificity ofthe interaction between lysine and arginine in chick
nutrition, in the light of theconcept of agent and target advanced
by Lewis (1965). Diets were designed in whichthe level of
methionine, tryptophan, histidine, or threonine was
appreciablyinadequate, while the arginine concentration in each
diet was marginally satisfactory.Excess lysine was added to these
diets in a standard sequence.
The profound ill-effects induced by excess lysine were, in all
experiments,alleviated only by arginine and not by the amino acids
originally limiting in thecontrol diets. The findings support the
existence of an unique relationship betweenlysine and arginine.
INTRODUCTION
Although there is a considerable body of evidence to suggest the
existence ofan interrelationship between lysine and arginine in
chick nutrition (O'Dell, Laerdal,Jeffay and Savage, 1958; Jones,
1961, 1962, 1964; Smith and Lewis, 1966) thedegree and extent of
specificity of this interaction has remained largely
unresolved.Lewis (1965) has proposed a concept of agent and target
to account for this relation-ship: the agent is the amino acid
which precipitates the ill-effects on growth whenadded in excess in
the diet (in this case lysine). The target is the amino acid
whichmust be added to counteract the phenomenon (in this instance,
arginine).
The specificity of the interaction between lysine and arginine
has been examinedin this study in relation to the concept of
interacting pairs advanced by Lewis (1965).In particular, the
ability of arginine to alleviate the ill-effects exerted by
excesslysine was considered under varying conditions of dietary
amino acid balance.
MATERIALS AND METHODS
Housing and management of experimental animalsThe experiments
were carried out using sexed Cobb broiler chicks (White
Cornish x White Rock).1 Present address: Department of
Agricultural Biochemistry, The East of Scotland College of
Agriculture,
West Mains Road, Edinburgh, 9.299
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300 J. P. F. D MELLO AND D. LEWIS
The chicks were housed in cages in a flat-roofed windowless,
insulated roombuilt within a larger building. The air temperature
was thermostaticallycontrolled.
Lighting was provided by means of three 100W white bulbs placed
at equalintervals along the centre of the ceiling. Ventilation was
controlled by means ofan electric extractor fan.
Sixteen blocks of 6 cages were housed in the room; each cage
being 38 cm long,30-5 cm wide and 25-4 cm high. The detachable
fronts of the cages consisted ofvertical galvanised metal bars
placed 3-2 cm apart. A metal barrier which couldbe moved up or down
these bars held the food and water containers in position.Beneath
the floor of each cage was a polythene droppings tray.
At the beginning of an experiment, 8-d-old cockerels were placed
in each cage.During the first week of life of the chicks the
temperature was maintained at 32 C,and was subsequently reduced by
2-5 C each week. Ventilation during the firstweek was by seepage
only. Additional ventilation in the following weeks was effectedby
means of the extractor fan. Lighting was provided continuously for
22 h eachday with the dark break occurring from 02.00 h to 04.00
h.
The chicks were offered food and water ad libitum. During the
first week, thechicks received a commercial-type starter diet. At
the end of this period, theexcessively light and heavy birds were
discarded. Those animals within the weightrange of 90 to 120 g were
selected at random using tables of random numbers(Fisher and Yates,
1963). The number of birds in each cage was reduced to four;weighed
quantities of the experimental diets were then offered. The animals
wereweighed individually at the end of each experiment2 weeks after
introduction tothe experimental diets.
Parameters of observationsLive-weight gain. The main parameter
of observation used in these studies was
the assessment of live-weight gain. This choice was based on the
premise that thereis good correlation between nitrogen gain and
live-weight gain in the growing animal.Unless the composition of
the chick in terms of the proportions of fat, lean or bonebecomes
important, live-weight gain remains the most convenient index of
adequacyof a dietary regime. In these experiments, gain in weight
was expressed as gainper animal per day (g/d), and represented a
mean of four replicate groups of fouranimals per replicate.
Food consumption and efficiency of food conversion. Food intake
was measured attimes coincident with the measurements of growth or
of nitrogen retention. Theefficiency of food conversion was
expressed as g gain/g of food ingested.
Nitrogen retention. The growth data in some experiments were
supported byrelevant observations on nitrogen-retention during the
last 3 d of each experiment.On the 18th d of an experiment the
plastic droppings tray beneath each cage wascleaned; 450 ml of o-i
N H2SO4 were placed in each tray. At the same time duringeach of
the 3 subsequent days, the contents of each tray were transferred
quantita-tively into a Waring blender and homogenised to an even
consistency after dilutingto an appropriate volume. A 15 ml sample
of the homogenate was placed directlyinto a Kjeldahl flask and the
nitrogen determined. Relevant food consumptionrecords were also
kept during each of the 3 d of the nitrogen balance period.
Samples
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INTERRELATIONSHIP BETWEEN LYSINE AND ARGININE 301
of the diets were analysed for nitrogen by the Kjeldahl
procedure. The resultswere expressed as g of nitrogen retained/g of
nitrogen ingested.
Plasma amino acid status. At the termination of each experiment
food was with-drawn for 10 h. The animals were re-offered the
appropriate diets for 2 h, afterwhich they were subjected to
another fast of 2 h duration. Blood was then withdrawnby cardiac
puncture from one chick from each replicate chosen at random,
andcollected in a 10 ml centrifuge tube lined with sodium oxalate
(BDH, Analar grade).After centrifugation the plasma was decanted,
the supernatants from each replicateof each treatment were pooled
and stored at 5 C until deproteinisation withabsolute alcohol. This
was used in preference to other methods since pH of theresultant
sample remained unaffected by this procedure arid consequently
offeredno interference in the subsequent amino acid analysis. The
protein-free plasmafiltrate was dried under vacuum in a rotary
evaporator and taken up in 2 ml of asolution of 10 per cent sucrose
in o-i N HC1: 1 ml of this sample was quantitativelyanalysed for
amino acids by ion-exchange chromatography using the
Techniconautomatic amino acid analyser. The value for each amino
acid was expressed asJU, moles/100 ml of plasma.
Experimental design and statistical analysis of resultsAll
experiments were conducted in the form of a randomised block
design.
Four replicates of each treatment were used, with the treatments
randomised withineach replicate group to offset effects of
temperature variation within the roomhousing the chicks.
Statistical evaluation of the significance of the results was
performed on allgrowth, efficiency of food conversion, and nitrogen
retention data. The results ofeach experiment have been illustrated
in tables of means, the significance beingindicated by the standard
error of means (S.E.M.) and the least difference betweenmeans
significant at the 5 per cent level of probability (L.S.D.).
The plasma amino acid data have not been subjected to
statistical analysissince determinations were of necessity limited
to one sample per treatment. Inmost instances, trends were observed
which confirmed gross observations and theconclusions drawn from
such observations. In no cases were conclusions basedentirely upon
the strength of evidence given by plasma amino acid data.
Experimental dietsThe diets were composed of conventional
ingredients, and were offered in a
ground form. An average of about 20 per cent crude protein (N x
6-25) was main-tained in all experimental diets. Energy status of
the diets within each experimentwas constant at around 3100 kcal
(metabolisable energy)/kg. It was ensured thatthe basal diets used
supplied all known essential nutrients other than those understudy,
at a level optimal for chick growth, by following the
recommendations of theAgricultural Research Council (1963) and the
National Research Council (1966)with judiciously selected margins
of safety. The values of amino acid content ofingredients used in
the preparation of the diets were those described by Lewis,Smith
and Payne (1963). The determination of the precise amino acid
compositionof the ingredients or of the basal diets was considered
unnecessary in the present
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302 J. P. F. D MELLO AND D. LEWIS
study since any deficiencies of amino acids were in every
instance tested by approp-riate dietary supplementation. The
various supplements of amino acids wereeffected by means of pure
crystalline amino acids; arginine-HCl, tyrosine, lysine-HC1,
histidine-HCl and leucine were supplied in the L form. Valine,
methionine,threonine, tryptophan and isoleucine were provided in
the DL form: the isomers ofthese amino acids can be utilised by the
chick (Fell, Wilkinson and Watts, 1959).In several experiments, the
desired degree of deficiency of an amino acid couldnot be achieved
when all the protein was derived from an intact source. In
suchinstances a variable proportion of the protein ranging from 16
per cent to 18 percent was supplied by conventional ingredients,
the remainder being provided in theform of synthetic essential
amino acids and glutamic acid.
TABLE I
Composition of the mineral and vitamin supplement, expressed in
termsof the final concentration contributed to the diet
MineralsCalciumPhosphorusSodiumChlorineManganeseZincIronCopperIodineCobaltMolybdenumSelenium
0-85 per cent0-30 per cento-ia per cent0-18 per cent.
70 mg/kg50 mg/kg20 mg/kg2 mg/kg1 mg/kgo-i mg/kg2 mg/kgo-i
mg/kg
Vitamins,Vitamin AVitamin D3Vitamin ECholine chlorideMenadione
sodium bisulphiteCalcium pantothenateRiboflavinFolic acidVitamin
BXJNicotinic acidProcaine penicillinPancoxin (coccidiostat)B.H.T.
(antioxidant)
etc.
6000 i.u./kg1500 i.u./kg
4 mg/kg500 mg/kg
5 mg/kg10 mg/kg4 mg/kg2 mg/kgo-oi mg/kg
20 mg/kg10 mg/kg0-0125 Per cent0-0125 Per c e n t
Adequate supply of minerals, vitamins, antibiotics, coccidiostat
and anti-oxidants were ensured by the inclusion in the diets of a
mineral and vitaminsupplement (Table 1). Unidentified growth
factors were provided by the incorpora-tion in all diets of 3 per
cent dried whey.
The ingredients and amino acid composition of the basal diets
are listed inTable 2. Since adverse effects of amino acids are more
readily observed in dietslow in protein or lacking in individual
essential amino acids, most diets in the presentstudy were designed
to be deficient in one or two essential amino acids.
The experimental programme was conducted in two phases: in
experiments1 and 2, the occurrence of the interaction between
lysine and arginine was examined;experiments 3-6 were concerned
with examining the specificity of this interaction.The basal diet
used in experiment 1 was considered to be marginally adequate
inarginine at 1-20 per cent of the diet, and fully adequate in all
other essential con-stituents. This was verified by the addition of
arginine to the basal diet; othertreatments constituted the
addition of two levels of lysine in excess of its requirements(o-6
per cent and o-8 per cent of the diet of lysine). The aim of this
experiment wasto examine the consequences of excess lysine
intake.
Experiment 2 was designed to investigate the efficacy of
arginine in alleviatingthe stress induced by excess dietary lysine
by following growth and plasma aminoacid patterns. A basal diet
calculated to be inadequate in arginine (0-87 per cent
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INTERRELATIONSHIP BETWEEN LYSINE AND ARGININE 3O3
of the diet) was employed. The treatments included: basal diet
alone; basal +arginine; basal + lysine; basal + lysine +
arginine.
The remaining experiments (3-6) were conducted with the aim of
examiningthe specificity of the lysine-arginine interaction; all
were variations on a commontheme. A basal diet limiting in an
essential amino acid other than arginine wasprepared. A standard
sequence of treatments to this control diet followed, involvingthe
testing of the basal diet to ensure the designed sequence of
limitation of theessential amino acids; other treatments
constituted the addition of excess lysine tothe basal diet and
subsequent testing to investigate which amino acid was effectivein
alleviating the consequent growth retardation.
TABLE 2
Experiments j-6: Ingredients and composition of basal diets.
{Composition is expressed as percentage of air-dry diets.Amino acid
composition derived from values described by Lewis et al. (1963),
and includes amino acids added as supplements)
Maize mealWheat mealSoyabean mealGround nut mealMaize gluten
mealDried wheyMinerals and vitaminsFat (Mazola)Essential amino acid
mixture plus
glutamic acid
Amino acid
contentArginineGlycineHistidineLeucineIsoleucineLysineMethionine+cystinePhenylalanine
+ tyrosineThreonineTryptophanValine
Nx6-25 (determined)
1
64-0
25-5
5-o3-02-5
1-201-22o-43I-8I0-84I ' l lo-861-580-840-281-03
20-03
2
25-043-o
3'521-0
3-02-52-O
. . .
0-871-23o-432-45-93i - n0*91i-680-830-240-96
20-06
Experimental diets
3
70-5
8-5u - 53-02-5
4-0
0-901-220-482-350-87I ' l O0-581-84o-860-25I'OI
20-08
425-043-o
3'52I-O
3-02-52-O
. . .
0-871-23o-432-45-93I ' l l0-91i-680-830-150-96
20-06
5...
68-516-o
...
...
32-55-o
5-o
o-881-220-301-44o-86I'lO0-89'570-820-26o-99
19-94
620-050-0
. . .
7-59-03 o
2-53-0
5-0
0-851-220-401-63o-86I ' l O0-89i-59o-550-250-97
20-00
In the first of these experiments (experiment 3), the basal diet
was preparedfirst limiting in the sulphur amino acids (0-58 per
cent of the diet) and second limitingin arginine (0-90 per cent of
the diet). All other essential amino acids were providedat adequate
concentrations, including lysine (at I-IO per cent of the diet).
Eighttreatments followed: control alone; basal + arginine; basal +
methionine; basal +arginine + methionine; basal + excess lysine;
basal + excess lysine + arginine; basal+ excess lysine +
methionine; basal 4- excess lysine + arginine + methionine.
The basal diet employed in experiment 4 was designed to be first
limiting intryptophan (0-15 per cent of the diet) and marginally
inadequate in arginine (0-87per cent of the diet). A similar
sequence of treatments to experiment 3 was imposedon this control
diet, the supplements of methionine being replaced by additions
oftryptophan.
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304 J. P. F. D'MELLO AND D. LEWIS
Experiment 5 was conducted in order to provide additional
evidence of a specificinteraction between lysine and arginine, by
following the fate of amino acids inplasma. The basal diet was
designed to be first limiting in histidine (0-30 per centof the
diet) and second limiting in arginine (o-88 per cent of the diet).
The treat-ments followed the standard pattern: basal diet alone;
basal + arginine; basal-t-arginine + histidine; basal + lysine
(excess); basal + lysine + arginine; and basal +lysine +
histidine.
In the final investigation of the specificity of the
lysine-arginine interaction(experiment 6), further metabolic
support for the growth observations were soughtby measurement of
nitrogen-retention in addition to plasma amino acid status.The
basal diet was prepared deficient primarily in threonine (0*55 per
cent of thediet) and marginally lacking in arginine (0-85 per cent
of the diet). The followingsequence of treatments was imposed:
basal diet alone; basal + arginine; basal4-threonine; basal +
arginine + threonine; basal + lysine (excess); basal + lysine
+arginine; basal + lysine 4- threonine; and basal + lysine +
arginine 4- threonine.
RESULTSExperiments 1-2: Occurrence of the lysine-arginine
interaction. The results of experi-
ment 1 are shown in Table 3. The basal diet was clearly not
limiting in arginineTABLE 3
Experiment 1: Effect ofsupplementation ofarginine and ofexcess
lysine on mean live-weight gain (g/d), and efficiency offood
conversion {g gainjgfoodingested) duringthe period J-SI d
Values represent mean of 4 replicate groups of 4 chicks each.
Basal dietmarginally adequate in arginine, fully adequate in all
other essential
amino acids
TreatmentBasal dietBasal+o-2 per cent L-arginineBasal+0-6 per
cent L-lysineBasal+o-8 per cent L-lysine
S.E.M.L.S.D. (P
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INTERRELATIONSHIP BETWEEN LYSINE AND ARGININE 305
nitrogen retention. However, this reversal was not complete,
indicating that excesslysine in some manner altered the arginine
requirement of the chick.
The plasma amino acid data relevant to experiment 2 are shown in
Table 5.As expected on supplementation of the basal diet with
arginine or lysine, there wasan accumulation of these amino acids
in plasma. However, the addition of lysine
TABLE 4
Experiment 2: Efficacy of arginine in alleviating the growth
depression by excess lysine. Responsemeasured in terms of
live-weight gain {gjd), efficiency of food conversion (g
gainjgfoodingested),and nitrogen retention (g JV retainedjg JV
ingested), during the period j-21 d
Values represent means of 4 replicate groups of 4 chicks each. .
Basal diet deficient inarginine
LiTreatment
Basal dietBasal+0-3 per cent L-arginineBasal+0-6 per cent
L-lysineBasal + lysine+arginine
S.E.M.L.S.D.
Live-weightgain
17-618-76 7
H-9o-43
t-3
Efficiency offood conversion
0-56o-590-36o-530-O20-05
Nitrogenretention
'59o-590-500-58o-oi0-03
to the diet also caused a lowering of the arginine levels in
plasma. Other aminoacids in plasma remained relatively constant
except glycine which also showed amarked depression on addition of
excess lysine to the diet; histidine, a basic aminoacid like
arginine and lysine, also appeared in considerably diminished
quantitiesin plasma. An interesting feature of the plasma amino
acid data is that although
TABLE 5
Experiment 2: Effect of lysine and arginine supplementation on
levels of selected amino acids in plasma (n moles/100 ml)Values
represent single determinations of pooled samples
Plasma amino acid levels (fi moles/100 ml)
Hist- Iso- Thre-Treatment Arginine idine Lysine Leucine leucine
Valine Glycine onine
Basal diet 4-5 19-0 28-5 39-8 11-5 16-8 74-3 128-9Basal+0-3 per
cent 18-6 13-2 34-4 44'0 11-3 14-5 83-0 83-7
L-arginineBasal+0-6 per cent
L-lysine 4-2 12-4 46-8 20-4 8-6 14-1 46-9
92-4Basal+lysine+arginine 4-8 8-3 69-2 2i-o 8-0 12-3 42-9 86-6
additional arginine alleviated to a large extent the
growth-depressing effects ofexcess lysine, it did not alter the
concentrations of lysine in the plasma, therebycasting some doubt
on the reciprocity of the interaction.
Experiments 3-6: Specificity of the lysine-arginine interaction.
The results of the initialexperiments suggested that the
interaction between lysine and arginine requiredfurther
investigation particularly in terms of its specificity. Accordingly
the nextphase involved experiments designed to examine alternative
target amino acids.These experiments were based on the premise that
in specific interactions, the effectivetarget amino acid would be
sensitive to a surplus of the agent even if the targetwere not
itself first limiting in the diet.
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306 j . P. F. D'MELLO AND D. LEWISThe live-weight gain and
efficiency of food conversion data of experiment 3
are listed in Table 6. The basal diet was deficient primarily in
methionine as shownby the response to methionine alone, but not to
arginine alone. The simultaneousaddition of methionine and arginine
to the basal diet yielded the best growthperformance (P
-
INTERRELATIONSHIP BETWEEN LYSINE AND ARGININE
TABLE 7
Experiment 4: Specificity of the interaction between lysine and
arginineeffect of supple-menting first and second limiting amino
acids on live-weight gain (gjd), and efficiencyof food conversion
(g gainfgfood ingested), during the period 7-21 d
Each figure in the table is a mean of 4 replicate groups of 4
chicks each. Basaldiet first limiting in tryptophan and second
limiting in arginine
307
Treatment
Basal dietBasal+o-25 per cent L-arginineBasal+0-10 per cent
DL-tryptophanBasal+arginine+tryptophanBasal+o-6 per cent
L-lysineBasal+lysine + arginineBasal+lysine +
tryptophanBasal+lysine+arginine+tryptophan
S.E.M.L.S.D. (P
-
308 j . P. F. D'MELLO AND D. LEWISunchanged. The concentration
of most other amino acids increased marginally onaddition of excess
lysine.
Additional metabolic support for a specific relationship between
lysine andarginine was provided in the final investigation
(experiment 6; Tables 10 and n ) .
TABLE IO
Experiment 6: Specificity of the interaction between lysine and
arginineeffect of supplementing first andsecond limiting amino
acids on live-weight gain (gjd), efficiency of food conversion (g
gainjg food in-gested), and nitrogen retention (g N retained)g N
ingested), during the period y-si d
Each value in the table is a mean of 4 replicate groups of 4
chicks each. Basal diet cal-culated to be first limiting in
threonine and second limiting in arginine
TreatmentBasal dietBasal+0-3 per cent L-arginineBasal+0-3 per
cent DL-threonineBasal+arginine + threonineBasal+o-6 per cent
L-lysineBasal+lysine +
arginineBasal+lysine+threonineBasal+lysine+arginine+threonine
S.E.M.L.S.D. (P
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INTERRELATIONSHIP BETWEEN LYSINE AND ARGININE 309
to 7*4 /x moles/100 ml plasma, without imposing much alteration
on the threonineconcentration. Lysine status remained consistently
high in plasma when a surpluswas present in the diet, even when
arginine supplementation corrected the growthretardation.
DISCUSSIONSince there is essentially no storage of amino acids
in the body, it has been
frequently assumed that any surplus ingested and not
subsequently utilised inprotein synthesis is disposed of without
impairing growth. It is now acknowledgedthat in most instances a
surplus of an essential amino acid will impose a limitationupon the
efficiency of nutrient utilisation commensurate with the magnitude
of thedeviation from a perfect balance. There are also recognised
to be certain occasionswhen a dietary excess of an amino acid or of
a mixture of amino acids will precipitatean ill-effect that is
totally disproportionate to the degree of imbalance. Harper(1958,
1964) grouped these effects into three categories: imbalances,
toxicities andantagonisms without examining in detail the
aetiological basis for this separation.Lewis (1965) suggested that
this classification could not be justified and proposedthat adverse
effects of amino acids could best be considered as specific
interactionsbetween pairs of amino acids. The interrelationship
between lysine and argininewas therefore examined in the light of
the agent-target hypothesis.
The results of experiments i and 2 demonstrate the occurrence of
the lysine-arginine interaction in chick nutrition. These findings
support the observations ofother authors (O'Dell et ah, 1958;
Jones, 1961, 1962 and 1964; Smith and Lewis,1966). Excess lysine
depresses growth severely when the arginine content of thediet is
marginally adequate. A concomitant supply of arginine in the diet
precludesthe onset of this phenomenon.
Information regarding the specificity of the interaction between
lysine andarginine is virtually absent due presumably to the
assumption that arginine is ageneral non-specific detoxifying amino
acid and as such is not involved in a specificinteraction
(Snetsinger and Scott, 1961). More recently, Boorman and
Fisher(1966), arrived at the conclusion that the lysine-arginine
interrelationship was notunique in spite of some contradictory
evidence. These authors showed that lysinewas singularly potent as
an agent of interaction when compared with other aminoacids in
excess in the diet. They further demonstrated that the ill-effects
of excesslysine were reversed by arginine supplementation in the
diet, but the adverse effectsof large quantities of methionine or
phenylalanine were not similarly alleviated.Since massive doses of
any amino acid might be expected to be toxic (Almquist,1952), mere
demonstration of a growth depression on addition of a surplus to a
dietneed not necessarily constitute a basis for establishing or
disputing the existence ofa particular interaction. Evidence of
complete reversal of the adverse effects of theagent by the target
amino acid should also be taken into account. It is thereforeonly
possible to decide upon the specificity of an interaction when the
above criteriahave been satisfied. It is conceivable that much of
the uncertainty regarding thespecificity of the interaction between
lysine and arginine is due to lack of evidenceconcerning the
significance and function of arginine as an effective target. For
thisreason the lysine-arginine pair was examined in detail for
possible alternative targetamino acids in the interaction
(experiments 3-6).
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310 j . p. F. D'MELLO AND D. LEWISThe results demonstrate
conclusively that the interaction between lysine and
arginine cannot be shown not to be specific. In experiment 3,
for example,methionine was tested as the alternative target amino
acid to arginine. It is clearthat the basal diet was primarily
deficient in methionine and only marginally lackingin arginine.
However, the addition of excess lysine reversed the sequence of
limita-tion in that the accruing growth depression was reversed
only by arginine and notby methionine therapy. The growth data of
experiments 4-6 confirm further thatthe disproportionate effects of
excess dietary lysine are alleviated by only arginineand not by the
alternative amino acids tested, although these were first limiting
inthe original diets. Tryptophan, histidine and threonine were each
tested as alter-native targets in these experiments due to
allegations that these amino acids couldinteract with lysine
(Winje, Harper, Benton, Boldt and Elvehjem, 1954; Henderson,Koeppe
and Zimmerman, 1953; Rosenberg, Culik and Eckert, 1959
respectively).In addition, histidine is a basic amino acid and may
share a common transportmechanism with lysine and arginine during
absorption from the intestine and duringrenal reabsorption
(Boorman, 1969). The possibility that histidine could
replacearginine as the target amino acid was therefore considered.
However, the growthobservations in the present study demonstrate
adequately that arginine alone is thetarget for lysine action.
Nesheim (1968) illustrated this specificity further in
studiesemploying two strains of chicks which differed substantially
in their requirementsfor arginine. Chicks1 with a high requirement
were less able to tolerate dietaryexcesses of lysine than were
chicks with a low requirement for arginine. Inaddition, excess
dietary lysine enhanced significantly the excretory output
ofarginine.
It is evident from the observations of Jones, Petersburg and
Burnett (1967)that the mechanism whereby the ill-effects of excess
dietary lysine are broughtabout is via an alteration of the
metabolic fate of arginine. The presentresults support these
observations. Surplus lysine precipitates a deficiency ofarginine
in spite of the impending lack in the basal diets of adequate
supply ofmethionine, tryptophan, histidine or threonine. This
accounts for the partialreversal of the ill-effects of excess
lysine by arginine supplementation in someof the present
experiments. Complete reversal would certainly be attained athigher
supplementary doses of arginine only (see D'Mello, Hewitt and
Lewis,1967).
The plasma amino acid data in experiments 5 and 6 support the
relevant growthobservations. Excess lysine in the diet induces a
specific drop in the plasma con-centration of arginine while
exerting no alteration on the metabolism of the alter-native target
amino acids tested (histidine in experiment 5; threonine in
experi-ment 6).
On the basis of evidence from the present study it is reasonable
to conclude thatin chick nutrition, lysine and arginine are
inextricably engaged in an uniqueinteraction.
ACKNOWLEDGEMENTS
One of us (J. P. F. D'M.) received a research studentship from
the Ministry ofAgriculture, Fisheries and Food. The technical
assistance of Miss C. Mott andMrs J. Hall is gratefully
acknowledged.
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INTERRELATIONSHIP BETWEEN LYSINE AND ARGININE 3II
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