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`
`THE FATE OF CREATINE WHEN
`
`ADMINISTERED
`
`TO MAN.
`
`BY ALFRED
`
`CHANUTIN.
`
`WITH
`
`THE ASSISTANCE
`
`OF LOREN
`
`P. GUY.
`
`(From
`
`the Laboratory
`
`of Physiological
`University.)
`
`Chemistry,
`
`University
`
`of Virginia,
`
`(Received
`
`for publication,
`
`October
`
`22, 1925.)
`
`has been the subject of
`in the organism
`fate of creatine
`The
`of the
`literature
`on this
`A recent, review
`investigations.
`many
`discloses
`conflicting
`ideas concerning
`creatine-creatinine
`subject
`to
`metabolism.
`The apparent
`inconsistencies
`may be ascribed
`several
`factors,
`the most outstanding
`being the varying quantities
`of creatine administered,
`usually quite small,
`together with
`the
`fact
`that administration
`of
`the substance
`was not continued
`over a sufficiently
`long period.
`In most cases
`the difficulty
`and
`expense of isolating pure creatine
`limited
`the amount which
`could
`be used
`for experimentation.
`since one may
`literature
`It
`is possible
`t.o omit much of the
`refer
`to the excellent
`review
`on this subject by Hunter
`(1).
`In
`his classic paper Folin
`(2) concluded
`that creatine and creatinine
`were
`independent
`of one another
`in metabolism,
`and
`that
`the
`former was utilized
`as a food. However,
`the
`results
`of
`later
`investigations,
`particularly
`those of Rose and Dimmitt
`(3) and
`Benedict and Osterberg
`(4), have shown
`that
`ingestion of creatine
`may
`lead to an increased output of creatinine
`in the urine.
`This
`evidence coupled with
`the fact
`that
`the creatinine
`found
`in mus-
`cular
`tissue
`is apparently
`derived
`from
`the
`“crcatine
`complex”
`by the action of enzymes,
`leads one to believe that urinary
`creati-
`nine must depend upon creatine as its precursor.
`has been
`The possibility
`of creatine
`acting as an anabolite
`fed on a
`shown by Benedict and Osterberg
`(-1). Dogs
`that were
`basal diet
`to which
`creatine was added not only gained weight
`but showed a marked
`positive
`nitrogen balance.
`The evidence
`obtained
`in
`these experiments
`seems
`to
`indicate
`that
`creat,ine
`may serve as a food, which would
`confirm
`the idea advanced by
`Folin
`(2) in 1906.
`
`29
`
`001
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`
`30
`
`Creatine
`
`with
`feeding experiments
`we carried out
`investigation,
`In this
`creatine on man.
`The results obtained show definitely
`that creat-
`ine and creatinine are not independent
`of one another
`in the body.
`Furthermore,
`these experiments
`demonstrate
`that a major portion
`of the creatine
`retained by the tissues may be converted
`to ereat-
`inine.
`Proof
`is given
`that creatine may spare protein.
`
`EXPERIMENTAL
`
`PROCEDURE.
`
`for the present experiments,
`served as the subjects
`The writers
`subsisting
`upon a creatine-free
`diet for 6 and 8 weeks
`respectively.
`The diet, consisting
`of shredded wheat,
`bananas, bread, butter,
`strawberry
`preserves,
`sugar, and milk,
`represented
`an intake
`of
`approximately
`3400 calories.
`The diet was adhered
`to strictly
`with
`respect
`to
`its composition.
`During
`the experiment,
`daily
`exercise was part of the
`regular
`routine.
`The
`type of exercise
`indulged
`in was not strenuous
`and varied
`from day
`to day.
`It was
`found
`that
`the nausea
`induced by
`the bitter
`taste of
`the creatine
`could best be avoided by dissolving
`it in hot weak
`tea.
`The creatine was
`taken about 2 hours after
`the noon meal.
`By recrystallizing
`commercial
`creatine
`twice,
`the resulting product
`was
`found
`to be pure upon analysis.
`to the
`The urines collected at the end of 24 hours were diluted
`same volume each day with
`a few
`exceptions.
`Total nitrogen
`was
`estimated
`by
`the macro Kjeldahl-Gunning
`method
`and
`creatinine
`by
`the Folin method.
`Creatine was determined
`by
`the autoclave method
`of Folin.
`Creatinine
`zinc chloride was
`used as a standard
`for
`the creatine
`and creatinine
`determina-
`tions.
`Ammonia
`nitrogen was estimated
`by
`the procedure
`of
`Van Slyke and Cullen.
`in nitrogen eyuilib-
`the body was
`that
`In order
`to be certain
`rium
`the experimental
`diet was begun 2 weeks before
`the
`first
`sample
`of urine was
`collected.
`After
`a satisfactory
`control
`period during which
`the urinary
`constituents
`studied were
`fairly
`constant,
`the administration
`of creatine was begun.
`in Tables
`The detailed
`results of the experiments
`are recorded
`I and II.
`The experimental
`periods
`lasted 59 and 44 days during
`which
`time 250 and 340 gm. of creatine,
`respectively,
`were
`in-
`gested.
`The analyses
`for July 12 cannot be considered because
`
`002
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`
` by guest on October 19, 2015
`
`A. Chanutin
`
`31
`
`of a mistake made
`the previous
`day.
`averages obtained
`
`of creatine on
`quantities
`unknown
`in taking
`These data have been omitted
`from
`the
`for
`this period.
`
`Results.
`
`by
`its retention
`feeding
`few days of creatine
`first
`the
`During
`is striking.
`A gradual decrease
`in retention may be
`the body
`noted, however,
`as the experiment
`proceeds.
`On the other hand,
`the extra creatinine
`eliminated
`rises slowly
`towards
`a maximum
`level.
`It
`is interesting
`to note
`that
`the smallest
`creatine
`and
`extra creatinine
`output during
`the entire experiment
`is obtained
`after
`the 1st day of creatine
`feeding.
`If creatinine
`is to be con-
`sidered as the end-product
`of creatine metabolism
`we must as-
`sume that creatine may be stored without
`any appreciable break-
`down.
`should
`to store creatine
`tissues
`the ability of the
`Apparently
`reach
`its maximum
`after
`the daily
`ingestion of 10 gm. of creatine
`over a period
`lasting more
`than a week.
`At
`this point Subject
`-4. C.
`(Table
`I) doubled
`the daily dose of creatine
`fed.
`The
`figures
`for
`the extra
`creatinine
`eliminated
`and
`the creatine
`re-
`tained
`both
`show marked
`increases.
`In
`fact
`the output
`of
`extra
`creatinine
`on
`the 2nd day of
`this period shows
`an in-
`crease of about
`160 per cent over
`the
`control
`period. We
`believe
`this
`figure
`represents
`the
`largest
`percentage
`creatinine
`output
`due to creatine
`feeding
`recorded
`in the
`literature.
`The
`unexpected
`increased
`retention
`of creatine
`indicates
`that
`the
`creatine
`reservoir may be larger
`than has been hitherto
`thought
`possible.
`As
`the period progresses
`the amount
`of creatine
`re-
`tained becomes smaller.
`time 160 gm. of
`At
`the end of an 8 day period during which
`creatine were
`taken,
`the daily dose was dropped back
`to 10 gm.
`Although
`this period
`lasted but 2 days evidence regarding
`creatine
`storage
`in
`the body
`is given.
`The excretion
`of creatine was
`greater
`than
`the intake on the 1st day.
`Subject L. P. G. continued
`to consume 10 gm. of creatine daily
`over a period of 34 days.
`In Table
`II
`it is seen that
`the creatine
`and creatinine excretion
`rose slowly until a fairly even level was
`reached at about
`the end of
`the
`first period.
`Although
`the
`
`003
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` by guest on October 19, 2015
`
`32
`
`Creatine
`
`-
`1
`-
`I 1 -
`I
`
`004
`
`Harvest Trading Group - Ex. 1122
`
`

`
`output.
`
`daily
`
`Average
`
`ingested.
`
`creatine
`
`No
`
`period.
`
`Fourth
`
`75.2
`
`output.
`
`daily
`
`Average
`
`creatinine)
`
`gm.
`administration.
`
`(8.62
`creatine
`
`daily.
`creatine
`of
`
`ingested
`10 gm.
`
`period
`
`Third
`
`0.65
`
`0.61
`0.69
`
`1.16
`
`1.51
`0.81
`
`-_
`
`--
`
`-0.12
`
`0.47
`
`output.
`
`daily
`
`Average
`
`45
`
`1.93
`
`4.23
`
`.?t
`G
`F
`
`0
`
`.+
`
`creatinine)
`
`gm.
`administration.
`
`(17.24
`
`ingested
`20 gm. of creatine
`
`daily.
`
`of creatine
`
`period
`
`output.
`
`daily
`
`Second
`
`Average
`
`Downloaded from
`
`http://www.jbc.org/
`
` by guest on October 19, 2015
`
`74.0
`
`13
`
`1 91
`1.19
`1.23
`1.95
`2.15
`2.37
`2.54
`2.08
`
`--
`
`0.60
`/
`-
`0.81
`,
`0.81
`I
`0.75
`I
`0.66
`I
`D.71
`I
`
`_
`
`2.21
`3.94
`3 9S
`4.83
`3.66
`5.00
`5.75
`4.45
`
`4.54
`
`2.83
`3.80
`4.72
`4.64
`5.00
`
`averaged.
`
`not
`
`day
`
`for
`
`* Figures
`
`-0.70
`
`1.55
`
`0.68
`2.42
`
`--
`
`8.73
`
`8.15
`9.32
`
`13.01
`--
`15.03
`13.30
`13.26
`12.41
`13.58
`12.24
`11.49
`12.79
`
`4.08
`
`5.79
`4.82
`3.90
`3.98
`3.62
`
`2.16
`
`3.71
`
`0.414
`
`7.58
`
`2.12
`2.20
`
`2.67
`
`3.02
`2.32
`
`2.80
`4.62
`
`0.408
`0.420
`
`8.03
`7.14
`
`__-~-
`
`620
`490
`
`11.43
`--
`11.17
`11.69
`
`0.429
`
`9.73
`
`0.429
`0.429
`
`9.48
`9.99
`
`--
`
`670
`940
`
`3.44
`
`16.45
`
`0.422
`
`3.42
`2.70
`2.74
`3.46
`3.66
`3.88
`4.05
`3.59
`
`18.45
`16.00
`16.00
`15.87
`17.24
`16.12
`15.54
`16.38
`
`0.487
`0.386
`0.398
`0.381
`0.414
`0.420
`0.445
`0.445
`
`12.37
`----
`12.31
`12.88
`12.37
`11.80
`12.37
`12.12
`12.56
`12.56
`
`1,275
`960
`930
`860
`990
`780
`1,240
`1,200
`
`2.10
`
`6.19
`
`0.471
`
`9.14
`
`-
`2.32
`2.32
`2.26
`2.17
`2.22
`
`8.11
`7.14
`6.16
`6.15
`5.84
`
`0.448
`0.473
`0.532
`0.431
`0.420
`
`9.46
`8.96
`9.02
`9.13
`8.82
`
`---
`
`650
`710
`735
`610
`715
`
`29
`28
`
`“
`July
`
`27
`26
`
`“
`July
`
`25
`24
`23
`22
`21
`20
`19
`18
`
`17
`16
`15
`14
`13
`
`“
`“
`“
`“
`“
`“
`“
`July
`
`“
`“
`“
`“
`July
`
`005
`
`Harvest Trading Group - Ex. 1122
`
`

`
`w
`
`Downloaded from
`
`http://www.jbc.org/
`
` by guest on October 19, 2015
`
`68.5
`68.5
`ko.
`
`_
`
`gm.
`
`gm.
`
`gm.
`
`!3m.
`-
`
`L. P. G.
`
`Creatine.
`
`Ingested
`
`of
`
`II.
`
`-
`
`Fate
`TABLE
`
`Subject
`2.
`
`as creatinine.
`
`-
`are expressed
`
`creatine
`
`for
`
`figures
`
`The
`
`Experiment
`
`output.
`
`daily
`
`Average
`
`given.
`
`creatine
`
`No
`
`69.5
`
`of 7 days.
`
`period
`
`Preliminary
`
`0.37
`0.61
`0.24
`0.21
`
`5.20
`5.21
`6.15
`6.80
`
`3.4
`3.4
`2.4
`1.8
`
`2.22
`1.98
`2.22
`1.85
`1.82
`
`1.61
`
`1.60
`1.54
`1.60
`1.65
`1.77
`1.49
`1.66
`
`-
`2
`0
`3
`2
`4
`
`1
`_-
`0
`4
`0
`5
`7
`9
`6
`
`1.61
`1.5
`1.61
`1.6
`1.7
`1.4’
`1.61
`
`8.4
`5.4
`5.6
`4.3
`3.6
`
`1.6
`
`0.43
`0.40!
`0.426
`0.381
`0.26(
`
`10.41
`9.18
`8.22
`8.37
`7.91
`
`1,810
`640
`670
`550
`575
`
`0.34:
`
`8.01
`
`0.40:
`0.37(
`0.28:
`0.33(
`0.262
`0.25(
`0.47(
`
`7.80
`7.20
`7.91
`8.42
`8.40
`7.69
`8.69
`
`--
`
`530
`520
`510
`620
`750
`770
`670
`
`12*
`11
`10
`9
`8
`
`7
`6
`5
`4
`3
`2
`1
`
`“
`“
`“
`“
`July
`
`“
`“
`“
`“
`“
`I‘
`July
`
`29
`June 20
`1926
`
`“
`
`Date.
`
`006
`
`Harvest Trading Group - Ex. 1122
`
`

`
`creatinine)
`
`gm.
`administration.
`
`creatinine)
`
`gm.
`administration.
`
`creatinine)
`
`gm.
`administration.
`
`output.
`
`daily
`
`Average
`
`126
`
`-
`
`(8.62
`of creatine
`
`daily.
`creatine
`
`ingested
`10 gm.
`
`period
`
`Third
`
`71.5
`
`71.0
`
`output.
`
`daily
`
`Average
`
`90
`
`(8.62
`of creatine
`
`daily.
`creatine
`
`ingested
`10 gm.
`
`period
`
`Second
`
`Average
`
` by guest on October 19, 2015
`
`70.7
`
`14
`
`output.
`
`daily
`
`(8.62
`
`daily.
`creatine
`
`of creatine
`
`period
`
`First
`
`Downloaded from
`
`ingested
`10 gm.
`
`http://www.jbc.org/
`
`1.03
`--
`0.85
`0.75
`1.02
`0.93
`1.13
`1.20
`1.23
`1.17
`0.91
`1.11
`
`1.22
`
`1.61
`2.43
`1.05
`0.67
`0.63
`1.27
`0.93
`1.25
`1.23
`1.11
`
`0.62
`
`0.91
`0.86
`1.04
`0.63
`0.77
`
`0.816
`
`0.55
`0.04
`2.93
`1.20
`2.26
`
`-3.97
`
`1.45
`1.07
`0.51
`2.12
`
`1.35
`
`0.61
`
`-0.12
`
`1.08
`1.34
`0.96
`1.88
`1.54
`2.02
`2.41
`1.73
`
`4.48
`
`1.72
`2.67
`3.33
`4.36
`4.90
`
`7.80
`--
`8.07
`8.56
`5.69
`7.42
`6.36
`12.59
`7.16
`7.55
`8.11
`6.50
`
`7.27
`-___
`8.01
`8.74
`7.54
`7.28
`7.66
`6.74
`7.08
`6.58
`6.21
`6.89
`
`4.14
`--
`6.90
`5.95
`5.29
`4.26
`3.72
`
`2.64
`
`10.44
`
`0.339
`
`2.46
`2.36
`2.63
`2.54
`2.74
`2.81
`2.84
`2.78
`2.52
`2.72
`
`10.53
`10.92
`8.32
`9.96
`9.10
`15.40
`10.00
`10.33
`10.63
`9.22
`
`0.325
`0.329
`0.336
`0.241
`0.386
`0.403
`0.405
`0.379
`0.263
`0.325
`
`2.85
`
`10.10
`
`0.305
`
`3.22
`4.04
`2.66
`2.28
`2.24
`2.88
`2.54
`2.86
`2.84
`2.72
`
`11.23
`12.78
`10.20
`9.56
`9.90
`9.62
`9.62
`9.44
`9.05
`9.61
`
`0.375
`0.292
`0.336
`0.400
`0.263
`0.151
`0.252
`0.336
`0.314
`0.330
`
`10.63
`_____~-
`10.86
`9.49
`10.88
`10.92
`10.75
`11.59
`10.92
`10.79
`10.66
`9.46
`
`9.70
`10.58
`10.69
`10.28
`10.40
`10.54
`10.90
`11.00
`10.95
`10.50
`
`10.55
`----
`
`860
`870
`1,080
`1,500
`2,290
`2,720
`1,720
`930
`860
`630
`
`730
`1,120
`840
`830
`845
`830
`930
`1,085
`940
`810
`
`2.24
`
`6.37
`
`0.423
`
`9.29
`
`2.52
`2.47
`2.65
`2.24
`2.38
`
`9.42
`8.42
`7.94
`6.50
`6.10
`
`--
`
`0.454
`0.504
`0.646
`0.632
`0.526
`
`9.60
`9.48
`11.05
`10.24
`8.93
`
`--
`
`685
`725
`1,100
`640
`520
`
`6
`5
`4
`3
`2
`1
`31
`30
`29
`28
`
`27
`26
`25
`24
`23
`22
`21
`20
`19
`18
`
`17
`16
`15
`14
`13
`
`“
`“
`“
`“
`“
`
`Aug.
`“
`“
`“
`July
`
`“
`“
`“
`“
`“
`“
`“
`“
`“
`July
`
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`July
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`Harvest Trading Group - Ex. 1122
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`Harvest Trading Group - Ex. 1122
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`

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` by guest on October 19, 2015
`
`A. Chanutin
`
`37
`
`variations
`daily
`slight
`show
`elimination
`for creatinine
`figures
`the averages
`ob-
`throughout
`the
`remainder
`of the experiment,
`tained
`for
`the various
`periods
`correspond
`closely.
`On
`further
`analysis
`of
`the data
`it will be seen
`that
`the amount
`of extra
`creatinine
`eliminated
`is almost
`the same as that of creatine
`re-
`tained
`(in terms of creatinine).
`During
`the
`first period 14 per
`cent of the creatine
`retained was
`recovered
`as extra
`creatinine.
`The second,
`third,
`and
`fourth
`periods
`show a conversion
`of 90,
`126, and 85 per cent.
`In Subject A. C. 45 per cent of the retained
`creatine
`is
`converted
`to creatinine
`during
`the second period.
`These data would
`lead us to conclude
`that a considerable
`portion
`of the creatine
`retained by
`the body may be transformed
`to its
`anhydride
`during
`the metabolic
`cycle under
`the conditions
`of
`these experiments.
`that creatine ap-
`(5) showed
`and Hawk
`The work
`of Fowler
`pears
`in the urine of normal adults after copious water drinking.
`Large quantities
`of water were drunk
`by Subject L. P. G.
`to
`note what effect it would have on creatine excretion.
`On August
`1 this subject
`secreted 2720 cc. of urine which was accompanied
`by an increase over
`the preceding
`day of more
`than 5 gm. of
`creatine.
`An almost corresponding
`diuresis on the following
`day
`failed
`to produce
`this
`result
`again. No effect on creatinine
`excretion was noted.
`in terms of
`are summarized
`the results
`IV
`In Tables
`III and
`balance are
`for
`the nitrogen
`The
`figures
`nitrogen
`elimination.
`from
`ingested
`significant.
`In estimating
`the nitrogen
`derived
`creatine,
`it is necessary
`to
`include
`the extra creatinine.
`Hence
`the addition
`of the average
`for
`the basal
`total nitrogen plus
`the
`nitrogen
`of
`total
`creatine and extra
`creatinine
`should give
`the
`theoretical
`total
`nitrogen
`elimination.
`The
`results
`show
`that
`the figures obtained
`for total nitrogen are much
`lower
`than would
`be expected.
`The feeding of creatine
`seems
`to act as a protein
`sparer.
`Although
`the creatine
`retained
`is
`for
`the most part
`converted
`to creatinine
`(Subject
`L. P. G.),
`the evidence
`still
`points
`to a storing
`of nitrogen.
`Benedict
`and Osterberg
`(4)
`suggest
`that
`“creatine may cause nitrogen
`storage
`in the body
`far beyond
`that contained
`in creatine
`itself.”
`steadily
`increased
`During
`the experimental
`period both subjects
`in weight
`(Tables
`I and
`II).
`An
`increase of about 3 kilos
`in
`
`009
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`Harvest Trading Group - Ex. 1122
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`

`
`N elimi-
`extra
`
`N plus
`
`nated.
`crestinine
`
`Creatine
`
`?
`
`y.gEj
`?WW’
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` by guest on October 19, 2015
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`010
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`Harvest Trading Group - Ex. 1122
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`

`
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` by guest on October 19, 2015
`
`A. Chanutin
`
`39
`
`These
`ingestion.
`to creatine
`in some way
`related
`is
`increase
`and might stimulate
`further
`research under
`results are suggestive
`more carefully
`controlled
`conditions.
`
`DISCUSSION.
`
`metabolism must of
`the creatine-creatinine
`of
`A discussion
`necessity be of somewhat
`hypothetical
`nature because of the num-
`ber of unknown
`factors
`to be dealt with.
`In order
`to study
`this
`problem
`these experiments
`were made under
`fairly
`constant
`con-
`ditions by flooding
`the organism with a large excess of creatine.
`The present
`research has shown
`that when
`creatine
`is given to
`normal adults
`in large doses per OS, a definite
`transformation
`of
`creatine
`to creatinine
`is possible.
`No definite percentage
`trans-
`formation
`can be postulated
`since
`the
`reaction
`apparently
`de-
`pends entirely
`upon
`the equilibrium
`established
`in
`the
`“active
`No marked
`increase
`in extra
`creatinine
`is noted until
`tissue.”
`the body has retained much of the creatine administered.
`Ac-
`cordingly,
`it is not surprising
`that small doses, which undoubtedly
`can be easily retained
`in a creatine
`reservoir, would not be traced
`by analysis
`of the urine.
`After
`small doses, creatine may pos-
`sibly be stored and metabolized
`slowly,
`just as fat or glycogen
`which has been deposited
`in its
`respective
`depots.
`although
`The significance of creatine
`in the tissues
`is unknown,
`in disease,
`it is present
`in relatively
`large amounts.
`Its behavior
`lead one to
`muscular
`exercise, protein
`feeding, and fasting would
`assume
`that
`there
`is a close relationship with protein metabolism.
`These experiments
`suggest
`that creatine,
`in some manner, may
`under certain
`conditions,
`play a role in determining
`the nitrogen
`balance of the organism.
`It
`is unlikely
`that much,
`if any, crea-
`tine
`is converted
`to protein
`since extra creatinine
`continues
`to be
`excreted
`after
`creatine
`ingestion
`is stopped.
`The
`relationship
`of creatine
`storage
`to protein metabolism
`cannot be postulated
`without more definite evidence.
`roughly
`If creatine can be stored
`in the tissues we can calculate
`the quantity
`retained.
`Of
`the 340 gm. of creatine
`taken
`by
`Subject L. P. G., it
`is found
`that 38 gm. are held by
`the body
`at the end of the experiment.
`Subject A. C. retained 58 gm. of
`creatine
`after
`taking
`270 gm.
`The apparent
`discrepancy
`in
`results
`is due to the time
`in which
`the body was allowed
`t.o react
`
`011
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`
`40
`
`Creatine
`
`Since the subjects
`taken.
`of creatine
`quantities
`to the respective
`each weighed about 70 kilos,
`the creatine content of the muscles
`may be calculated
`roughly
`at about 115 gm. This would mean
`that
`there was increased storage
`in the muscles amounting
`to about
`33 and 50 per cent.
`This
`retention
`does not seem
`improbable
`in the light of the experiments
`of Folin and Denis
`(6) and Myers
`and Fine
`(7), who demonstrated
`that muscles
`could hold,
`tem-
`porarily,
`at least, even
`larger quantities
`of added creatine
`than
`have been noted
`in these experiments.
`of creatine
`The inability
`to discover
`the fate of small quantities
`is responsible
`for
`the
`theory
`that
`creatine
`is destroyed
`in
`the
`aliment.ary
`tract
`through
`bacterial action.
`Folin
`(2) was unable
`to
`find any
`trace of creatine
`in
`the
`feces after
`feeding.
`The
`experiments
`of Rose and Dimmitt
`(3)
`indicate
`that creatine
`is
`not decomposed
`in the alimentary
`tract since there
`is no appreci-
`able increase
`in urinary
`urea or ammonia.
`The
`figures obtained
`for
`the conversion
`of retained
`creatine
`to creatinine
`in
`these
`experiments would
`lead us to assume
`that creatine
`is completely
`absorbed
`from
`the alimentary
`tract,
`carried
`to
`the
`tissues,
`and either stored
`there or rejected at once and eliminated
`through
`the kidneys.
`is an active mass
`there
`that
`fact
`accepted
`It
`is a generally
`tissue where
`creatine
`is built up and stored as an unstable
`of
`complex
`form which
`apparently
`has an
`important
`role
`in
`the
`normal
`functioning
`of
`the protoplasmic
`mass.
`The organism
`under normal conditions
`apparently
`has its full quota of creatine.
`However,
`it seems
`that
`the tissues
`can completely
`store a small
`s.mount of ingested
`creatine during a limited period of feeding.
`Large amounts
`are only partially
`retained-a
`retention
`which
`depends entirely
`upon
`the period of administration.
`Metabolic
`studies would
`lead one to suggest
`that stored
`creatine may act
`as an anabolite
`in protein metabolism.
`We believe
`that an anal-
`ogy may be drawn
`between
`creatine
`and glucose metabolism.
`Small quantities
`of both
`these substances
`are completely
`retained
`by the body after being fed. Upon
`increasing
`the dosage, both
`substances will appear
`in the urine
`in amounts depending entirely
`on
`the quantities
`ingested.
`Glucose
`is stored
`as the polysac-
`charide glycogen and
`it
`is probable
`that creatine may be built
`up
`in a similar manner
`to a polycreatine
`compound.
`Whereas
`
`012
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`
`A. Chanutin
`
`41
`
`of
`the end-product
`to COZ and HzO,
`down
`is broken
`glucose
`is creatinine
`in all likelihood
`or some creati-
`creatine metabolism
`nine precursor.
`Undoubtedly
`both
`these
`reactions
`take place
`through
`the action of enzymes.
`Creatine may
`thus be stored
`as a reserve
`food material
`and utilized
`very
`slowly
`until
`the
`normal
`level
`is reached.
`
`SUMMARY
`
`AND
`
`CONCLUSIONS.
`
`tract
`the alimentary
`from
`of creatine
`1. The absorption
`There
`is no evidence of its bacterial
`pears
`to be complete.
`struction
`in the alimentary
`tract.
`increases after
`in man
`2. The creatinine
`content
`of the urine
`ingestion of large doses of creatine.
`Data are presented
`to prove
`that extra creatinine excretion
`is derived directly
`from
`the creatine
`fed.
`to indicate
`is presented
`3. Evidence
`direct action on nitrogen metabolism.
`
`that creatine has an in-
`
`ap-
`de-
`
`BIBLIOGRAPHY.
`
`ii, 586.
`1. Hunter, A., Physiol.
`1922,
`Rev.,
`2. Folin, O., in Hammarsten, O., Festschrift, Upsala, 1906, pt. 3, I.
`3. Rose, W. C., and Dimmitt,
`F. W., J. Biol.
`1916, xxvi, 345.
`Chem.,
`4. Benedict, S. R., and Osterberg, E., J. Biol.
`Ivi, 229.
`Chem.,
`1923,
`5. Fowler, C. C., and Hawk, P. B., J. Exp. Med.,
`1910, xii, 388.
`6. Folin, O., and Denis, W., J. Biol.
`1914, xvii, 493.
`Chem.,
`7. Myers, V. C., and Fine, M. S., J. Biol. Chem., 1913-14, xvi, 169.
`
`013
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`ARTICLE:
`THE FATE OF CREATINE WHEN
`ADMINISTERED TO MAN
`(cid:160)
`Alfred Chanutin and With the assistance of
`Loren P. Guy
`
`1926, 67:29-41.
`
`J. Biol. Chem.(cid:160)(cid:160)
`
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