Downloaded from https://academic.oup.com/ajcn/article-abstract/34/5/914/4431066 by Reprints Desk user on 21 May 2020
`
`Cysteine
`intravenous
`infants(cid:1)3
`
`supplementation
`feeding
`
`to cysteine-free
`regimens
`in newborn
`
`Stanley
`
`H.
`
`Zlotkin,4
`
`M.D.,
`
`M. Heather
`
`Bryan,5
`
`M.D.,
`
`and
`
`G. Harvey
`
`Anderson,6
`
`Ph.D.
`
`ABSTRACT
`newborn
`amino
`
`if cysteine
`determine
`To
`infant, growth
`parameters,
`nitrogen
`acid excretion
`of premature
`and
`term
`
`is an essential amino
`
`acid for the intravenously
`
`fed
`
`acid levels, and urinary
`sulfur amino
`plasma
`balance,
`infants were
`measured
`in the presence
`or absence
`of
`
`Control
`cysteine.
`infused
`methionine,
`carbohydrate,
`
`formulations
`intravenous
`lipid, minerals,
`vitamins,
`
`amino
`provided
`and
`trace elements
`
`adequate
`acids, including
`to all infants. Group
`and
`
`pair-matched
`
`comparisons
`
`showed
`
`that nitrogen
`
`retention, weight
`
`in length
`growth
`and
`change,
`h. The
`of 77 mg/kg/24
`supplementation
`by cysteine
`not affected
`were
`circumference
`head
`and
`age
`or
`of
`postnatal
`nitrogen
`retention
`was
`independent
`to
`alter
`failure of cysteine
`supplementation
`by 60% in the supplemented
`group
`was
`gestational age. Plasma
`‘/2 cystine concentration
`increased
`with a concomitant
`3-fold increase in urinary excretion
`of ‘/(cid:1) cystine
`not of urinary
`and
`taurine,
`but
`
`Cysteine-supplemented
`or cystathionine.
`methionine
`methyihistidine
`excretion
`compared
`to pair-matched
`
`protein catabolism
`muscle
`34: 914-923,
`1981.
`
`or an increase in muscle
`
`exhibited
`infants
`controls, suggesting
`have occurred.
`
`may
`
`mass
`
`in 3-
`increase
`a small
`that either an increase in
`
`Am.
`
`J. Clin.
`
`Nutr.
`
`KEY
`ance,
`
`WORDS
`amino
`
`acid
`
`cysteine supplementation,
`intravenous
`levels,
`3-methylhistidine
`excretion
`
`feeding, newborn
`
`infants, nitrogen
`
`bal-
`
`Introduction
`
`yet
`
`one
`
`only
`acids,
`cysteine
`contains
`Pharmacia,
`(Vamin,
`of
`cysteine
`absence
`14)
`(1,
`formulations
`due
`(2,
`6)
`is primarily
`oxidized
`of
`cystine,
`the
`and
`In
`older
`children
`to convert
`methionine
`enzyme
`cystathionase,
`ately
`called
`“nonessential”,
`can
`endogenously
`
`pre-
`and
`route
`oral
`surgical
`or
`nutrition is
`appropri-
`to
`allow
`devel-
`has
`sup-
`the
`that
`amino
`(3),
`and
`suitable
`of
`newborn,
`In
`
`term
`full
`both
`infants,
`Newborn
`the
`via
`fed
`routinely
`are
`mature,
`medical
`prohibited
`by grave
`unless
`emergencies.
`intravenous
`When
`the
`provided,
`the
`is to provide
`goal
`ate
`amount
`quality
`of
`nutrients
`and
`and
`for
`optimal
`extrauterine
`growth
`success
`opment.
`Although
`reasonable
`nutrition
`been
`achieved
`with
`parenteral
`port
`for
`newborns,
`it
`is
`recognized
`nutrient
`formulations
`available,
`2),
`acid
`mixtures
`(1,
`lipid
`emulsions
`(4,
`vitamin
`mixtures
`5) may
`be more
`for meeting
`nutritional
`requirements
`adult
`or
`growing
`child
`than
`of
`the
`particularly
`the
`premature
`newborn.
`study
`we
`have
`examined
`the
`newborn’s
`quirement
`for
`exogenous
`cysteine
`and
`the
`appropriateness
`of
`adding
`cysteine
`acid
`enteral
`amino
`formulations.
`All
`presently
`available
`intravenous
`amino
`formulations
`for
`pediatric
`use
`contain
`ture
`of
`nonessential
`essential
`
`i.e.,
`
`and
`
`the
`
`this
`re-
`hence
`to par-
`of
`the
`acid
`a mix-
`amino
`
`product
`manufactured
`quantity
`significant
`in
`Quebec).
`The
`Montreal,
`amino
`acid
`in
`crystalline
`hydrolysates
`protein
`poor
`solubility
`to
`the
`of
`cysteine
`(7).
`form
`who
`are
`able
`adults
`to cysteine
`via the
`cysteine
`is
`appropri-
`meaning
`that
`from
`methi-
`
`or
`
`be
`
`produced
`
`it
`
`Sick
`
`for
`
`and the Hospital
`Canada.
`Research
`Health
`
`Council
`Research
`
`of Can-
`Grant
`
`of Toronto
`the University
`‘From
`Ontario,
`Children,
`Toronto,
`2Supported
`by
`the
`Medical
`Ontario
`Province
`of
`ada,
`Ltd.
`Laboratories
`and
`Abbott
`(PR228)
`Anderson,
`H.
`G.
`to: Dr.
`3Address
`reprint requests
`FitzGerald
`Food
`Science,
`Department
`of Nutrition
`and
`Canada,
`M5S
`lA8.
`Building,
`University
`of Toronto,
`Food
`Ph.D.
`candidate,
`Department
`of Nutrition
`and
`Science,
`University
`of Toronto.
`Present
`address:
`Division
`of Clinical
`Nutrition,
`The
`Hospital
`for
`Sick
`Children,
`555
`University
`Avenue,
`Toronto,
`Canada,
`M5G
`1X8.
`5Department
`of
`Pediatrics.
`#{176}Department
`Nutrition
`and
`Food
`Science.
`
`of
`
`914
`
`The American
`
`Journal
`
`of Clinical
`
`Nutrition
`
`1981, pp. 9 14-923. Printed
`34: MAY
`© 1981
`American
`Society
`for Clinical
`
`in U.S.A.
`Nutrition
`
`Eton Ex. 1097
`1 of 10
`
`

`

`CYSTEINE
`
`NEEDS
`
`OF
`
`INTRAVENOUSLY
`
`FED
`
`NEWBORNS
`
`915
`
`and
`
`TABLE
`Subject
`
`1
`description*
`
`newborn
`fetus
`in the
`(8). However,
`onine
`cystathio-
`hepatic
`that
`infant,
`reports
`human
`me-
`converts
`normally
`enzyme
`that
`nase,
`low
`in
`or
`was
`absent
`to
`cysteine,
`thionine
`general
`a
`to
`has
`led
`10)
`(9,
`concentration
`exogenously
`be
`must
`cysteine
`acceptance
`“essential”
`an
`is
`therefore
`supplied
`however,
`activity,
`Cystathionase
`acid.
`amino
`gesta-
`and
`possibly
`with
`postnatal
`increases
`rate
`of maturation
`(1 1). Since
`age
`tional
`unknown
`in
`is
`enzyme
`system
`of
`this
`at which
`methionine
`infant,
`the
`age
`human
`also
`becomes
`adequate
`to cysteine
`conversion
`work
`From
`the
`pioneering
`unknown.
`remains
`the
`1940s
`to
`determine
`in
`Rose
`done
`requirements
`in
`adults,
`and
`amino
`has
`studying
`children,
`it
`Snyderman
`that
`abnormalities
`growth
`established
`retention
`of
`nitrogen
`occur
`decreased
`amino
`are
`excluded
`from
`acids
`essential
`Thus
`be
`predicted
`that
`it would
`diet
`(12).
`cannot
`be
`endogenously
`produced
`cysteine
`methionine
`in
`newborn
`premature
`from
`considerable
`improvement
`in
`nitro-
`infants,
`gen
`retention
`and
`growth
`would
`if cys-
`teine
`were
`added
`to
`intravenous
`acid
`mixtures.
`Based
`this
`prediction,
`on
`not
`on
`clinical
`reports
`its
`efficacy,
`is cur-
`of
`rently
`made
`available
`as
`an
`by
`one
`pharmaceutical
`manufacturer.
`study
`The
`purpose
`of
`the
`present
`cysteine
`examine
`the
`hypothesis
`that
`for
`essential
`amino
`acid
`the
`intravenously
`newborn.
`A cysteine-free,
`methionine-ade-
`quate
`intravenous
`amino
`acid
`mixture
`supplemented
`cysteine,
`and
`growth,
`trogen
`retention,
`plasma
`amino
`acids,
`urinary
`3-methylhistidine
`responses
`sured
`in premature
`infants.
`
`the
`
`that
`and
`
`by
`acid
`
`the
`
`with
`
`and
`
`term
`
`in
`
`and
`
`result
`amino
`but
`cysteine
`additive
`
`the
`
`by
`been
`and
`when
`the
`if
`
`was
`is
`
`to
`an
`fed
`
`was
`ni-
`and
`mea-
`
`Methods
`
`Subjects
`
`and
`
`experimental
`
`design
`
`infants were studied for a total of thirty-
`Twenty-eight
`periods. Seventeen
`of the infants were
`six 6-day
`feeding
`premature
`with a mean
`gestational
`age of 31 wk
`(range
`25
`to
`36) and
`11 were
`full term.
`Gestational
`age
`was
`calculated
`from
`the mother’s
`last menstrual
`period
`and
`by Dubowitz
`scoring
`(13). The
`average
`postnatal
`age at
`the beginning
`of the study
`was
`similar (range
`2 to 46
`days)
`in both
`groups.
`All infants were
`appropriate
`size
`for gestional age. The
`clinical diagnosis
`and
`description
`of the infants is shown
`in Table
`I. All of the infants
`received
`total intravenous
`nutrition
`for at least 6 days
`because
`of medically
`or surgically
`related
`conditions
`
`Downloaded from https://academic.oup.com/ajcn/article-abstract/34/5/914/4431066 by Reprints Desk user on 21 May 2020
`
`Cysteine
`supplementedt
`(n
`
`18)
`
`2231±391
`34.4 ±
`13.7 ±
`
`2.2
`5.5
`
`Controt(cid:1)
`(n
`
`-
`
`18)
`
`2141±357
`34.2
`± 2.0
`15.0
`± 5.6
`
`8
`3
`1
`2
`
`2
`2
`
`9
`5
`0
`0
`
`0
`4
`
`age (wk)
`age (days)
`
`hernia
`atre-
`
`Birthwt(g)
`Gestational
`Postnatal
`Diagnosis
`enterocolitis
`Necrotizing
`atresia
`Intestinal
`Diaphragmatic
`Tracheoesophageal
`sia
`perforation
`Bowel
`Gastroschisis
`* All
`values
`t Supplemented
`cysteine.
`:1:No
`cysteine
`control
`amino
`
`day
`
`are
`
`expressed
`
`with
`
`as mean
`
`±
`
`SE.
`
`an
`
`average
`
`of
`
`78
`
`±
`
`2 mg/kg!
`
`supplement.
`acid
`formulation
`
`is no
`There
`(Aminosyn).
`
`cysteine
`
`in the
`
`similar
`
`trace
`
`of
`
`a
`
`a
`
`and
`
`of
`
`not
`zero
`had
`received
`
`was
`
`oral
`
`feeding.
`(TPN)
`
`of
`or
`
`decision
`by
`
`to start
`The
`clinician
`the
`was made
`group.
`Infants
`the
`research
`blood
`transfusions
`were
`cx-
`
`total
`on
`
`prevented
`which
`nutrition
`parenteral
`independent
`the
`ward
`either
`plasma
`receiving
`from
`the
`study.
`cluded
`assigned
`alternately
`were
`study
`the
`chosen
`for
`Infants
`1).
`Infants
`(Table
`group
`or
`an experimental
`a control
`into
`formulation
`control
`received
`a
`both
`groups
`in
`L-amino
`a crystalline
`of
`which
`consisted
`of
`cysteine
`free
`Montreal,
`Laboratories,
`(Aminosyn,
`Abbott
`acid mixture
`fluid
`water,
`maintenance
`10% dextrose
`and
`in
`Quebec)
`(2.5 ml
`of
`to
`vitamins
`in
`(14),
`addition
`and
`electrolytes
`Quebec
`alter-
`Montreal,
`Laboratories,
`MV1,
`Arlington
`Lederle
`Products,
`Folbesyn,
`of
`2.5 ml
`with
`nating
`daily
`elements.
`This
`and
`minerals,
`Quebec),
`Montreal,
`average
`fluid
`an
`provide
`to
`planned
`was
`formulation
`480
`mg
`of
`included
`h which
`150 mh/kg/24
`intake
`h. Addi-
`kg/24
`per
`carbohydrate
`and
`15
`g of
`nitrogen
`Phar-
`(Nutralipid,
`lipid
`energy
`was
`provided
`as
`tional
`h with
`g/kg/24
`2.5
`Montreal,
`Quebec)
`at
`macia,
`Infusion
`h.
`kcal/kg/24
`total
`energy
`intake
`of 90
`planned
`infusion
`flow
`a peripheral
`vein
`using
`a continous
`was
`via
`in
`addition,
`The
`experimental
`group
`received,
`pump.
`hydrochloride
`supplement
`(L-cysteine
`hydro-
`cysteine
`76.8%
`cysteine,
`Abbott
`Laboratories)
`77 mg
`chloride,
`of
`cysteine/kg/24
`h. The
`control
`group
`did
`receive
`a
`cysteine
`supplement,
`therefore
`cysteine
`intake.
`Informed
`consent
`before
`parental
`administering
`supplement.
`cysteine
`the
`were
`periods
`study
`Within
`group,
`eighteen
`6-day
`each
`were
`period
`study
`completed.
`first
`3 days
`each
`The
`of
`(1, 15). During
`considered
`to be a period
`of adaptation
`pooled
`along
`the last 3
`days,
`urine
`was
`collected
`and
`with any
`stool, nasogastric
`or other drainage
`(excluding
`dermal
`losses) for analysis of total nitrogen
`by the micro-
`Kjeldahl
`method
`(16). Detailed
`intake records were
`col-
`lected
`for the study
`period
`thereby
`allowing
`for the
`calculation of nitrogen retention. N intake was calculated
`on
`the
`basis of each
`100 g of Aminosyn
`containing
`the study
`period
`routine
`he-
`15.84%
`nitrogen.
`During
`matological,
`biochemical,
`and
`clinical monitoring
`was
`
`Eton Ex. 1097
`2 of 10
`
`

`

`916
`
`ZLOTKIN
`
`ET
`
`AL.
`
`were
`infants
`as necessary.
`head
`circumference
`length
`and
`study
`and
`at
`the
`into
`the
`(300
`(cid:1)l)
`from
`heel
`samples
`were
`obtained
`vein
`in
`order
`to
`1 100
`on
`plasma
`amino
`
`maintained
`sured
`for
`before
`entry
`period.
`Blood
`or
`a
`peripheral
`between
`0900
`diurnal
`variation
`
`to
`
`Laboratory
`
`procedures
`
`negate
`acid
`
`weighed
`
`and mea-
`immediately
`of
`the
`study
`puncture
`sites
`the
`day
`the
`of
`levels.
`
`end
`
`on
`
`6th
`effects
`
`Downloaded from https://academic.oup.com/ajcn/article-abstract/34/5/914/4431066 by Reprints Desk user on 21 May 2020
`
`Calculation
`
`of
`
`cysteine
`
`intake
`
`In
`
`as
`
`essential
`an
`cysteine
`present
`of
`cysteine
`mothers
`milk
`from
`the
`reference.
`as
`g of
`protein/dh
`1.1
`(19).
`Assuming
`200 ml/kg
`40 mg
`could
`of
`
`of
`
`a
`
`amino
`investigate
`to
`order
`in mature
`concentration
`the
`acid,
`giving
`birth
`and
`human
`milk
`pooled
`Pooled
`mature
`was
`used
`prematurely
`and
`20 mg
`contains
`milk
`human
`g of protein!
`2.2
`g ofprotein
`per
`cysteine
`of
`pooled
`mature
`infant
`receiving
`an
`kg/day
`cysteine!kg/day.
`of
`would
`receive
`milk
`breast
`on
`been
`based
`have
`the
`calculation
`Alternatively,
`a
`premature
`infant
`the
`mother
`by
`milk
`produced
`This
`milk
`contains
`postnatal
`month.
`1st
`during
`the
`of
`1 .9 g of protein!dl
`(20).
`Assuming
`mean
`concentration
`3.8
`per
`g of
`protein
`and
`an
`intake
`of
`20 mg
`of
`cysteine
`which
`is
`possible
`if
`the
`infant
`g
`of
`protein/kg/day,
`his
`premature
`infant
`fed
`own
`a
`tolerates
`200
`mI/kg,
`receive
`76 mg
`of
`cystiene!kg!day.
`mother’s
`milk
`would
`Therefore,
`in
`the
`present
`study
`an
`amount
`equal
`that
`to
`figure
`provided.
`In
`order
`confirm
`the
`was
`cysteine,
`intake
`were
`receiving
`the
`planned
`of
`for
`total
`analyzed
`samples
`of
`infusate
`were
`was
`supplement
`content.
`The
`cystemne
`HCI
`under
`formulation
`added
`the
`amino
`acid
`to
`pharmacy
`hospital
`laminar
`flow
`hood
`in the
`air
`which
`h after
`given
`expiry
`time
`of
`72
`an
`samples
`random
`was
`discarded.
`Analysis
`of
`at
`and
`72
`h and
`one
`sample
`2 months
`24
`of
`addition
`revealed
`no
`change
`in total
`The
`supplemented
`group
`of
`infants
`the
`planned
`intake
`of
`cysteine.
`
`this
`to
`infants
`random
`cysteine
`originally
`a
`sterile
`and
`was
`the
`bag
`infusate
`the
`time
`content.
`received
`
`time
`of
`
`after
`cysteine
`therefore
`
`Statistical
`
`analysis
`
`and
`and
`
`outcomes
`The
`change
`included
`3-methyihistidine
`amino
`acid
`and
`postnatal
`The
`data
`were
`test
`for
`paired
`was
`also
`used
`
`levels.
`on
`age
`evaluated
`and
`where
`
`compared
`in weight
`excretion,
`In
`addition,
`nitrogen
`for
`nonpaired
`appropriate
`
`the
`nitrogen
`and
`
`between
`height,
`plasma
`the
`effect
`retention
`were
`significance
`by
`data.
`Regression
`(21,
`22).
`
`of
`
`groups
`two
`retention,
`urine
`sulfur
`gestational
`determined.
`the
`Student’s
`analysis
`
`Results
`
`Nitrogen
`
`balance
`
`nitrogen,
`total
`data
`Neither
`significantly
`received
`
`Mean
`rine,
`and
`retention
`groups.
`were
`groups
`electrolytes,
`groups
`Both
`nitrogen,
`of
`tion
`the
`infused
`56% of
`are
`similar
`to
`those
`study
`of
`infants
`fed
`tion
`containing
`similar
`and
`total
`calories
`(23,
`the
`nitrogen
`retention
`
`tau-
`cysteine,
`methionine,
`and
`nitrogen
`energy
`intakes
`are
`shown
`in Table
`2 for
`both
`nitrogen
`nor
`energy
`intakes
`In
`different.
`addition,
`both
`intakes
`similar
`of
`total
`fluid,
`and
`trace
`minerals
`elements.
`similar
`showed
`positive
`282 mg/kg/24
`h, which
`nitrogen.
`These
`retentions
`described
`in
`a previous
`an
`intravenous
`formula-
`quantities
`nitrogen
`of
`24)
`and
`parallel
`also
`expected
`in
`utero
`(25).
`
`reten-
`was
`
`centrifuged
`immediately
`was
`sample
`immediately
`and
`decanted
`plasma
`x g).
`the
`acid.
`After
`10% sulfosalicyhic
`to
`1:3 dilution
`8000
`x
`the
`supernatant
`was
`(5 mm
`g)
`immediately
`frozen
`at
`-70#{176}C to
`off
`and
`cysteine
`(17).
`At
`a
`hater
`content
`in
`il of
`125
`was
`applied
`to
`plasma
`of
`amino
`acid
`analyzer
`(Beckman
`Beckman
`model
`116/119).
`acid
`analyzer,
`by
`analysis
`for
`amino
`acid
`was
`prepared
`with
`x g)
`in a 1:1 dilution
`(15 mm at 3000
`equiva-
`centrifugation,
`the
`acid.
`After
`or
`the
`applied
`to
`the
`column
`urine
`was
`of
`acids
`in
`stored
`frozen
`at
`-20#{176}C. Amino
`was
`column
`were
`separated
`using
`a single
`urine
`were
`citrate
`buffers.
`Amino
`acids
`lithium
`citrate
`resin
`(59
`cm)
`with
`lithium
`a UR-30
`changed
`buffer
`(pH
`2.77,
`0.3 N) was
`initial
`sample
`2.85,
`0.3
`N)
`90 mm
`after
`(pH
`buffer
`was
`changed
`a third
`(pH
`second
`for
`250 mm after
`the
`beginning
`the
`run.
`The
`of
`was
`changed
`for
`lithium
`hydroxide
`(0.3
`N)
`run
`the
`beginning
`of
`the
`for
`regeneration
`The
`total
`time
`required
`for
`a
`complete
`regeneration
`was
`610
`mm.
`The
`initial
`the
`column
`38#{176}C,but
`beginning
`after
`of
`temperature
`increased
`to
`65#{176}Cfor
`the
`the
`run.
`system,
`cysteine
`elutes
`of
`glutamine
`and
`and
`separate
`from
`
`drawn
`alterations
`equivalent
`ofa
`
`the
`
`(5
`
`at
`
`was
`was
`this
`In
`proline,
`
`is
`
`#{189}
`
`blood
`Each
`8000
`mm at
`in
`a
`added
`centrifugation
`carefully
`prevent
`the
`date
`column
`the
`Spinco
`amino
`Pooled
`urine
`centrifugation
`15% sulfosalicylic
`lent
`of
`250
`(cid:1)l
`supernatant
`and
`plasma
`with
`system
`off
`eluted
`The
`buffers.
`second
`for
`the
`The
`infusion.
`1.2 N)
`4.13,
`buffer
`third
`560 mm
`after
`of
`the
`column.
`run,
`including
`temperature
`225 mm
`remainder
`between
`cystine.
`Aliquots
`methylhistidine.
`NaOH
`saturated
`in
`a dessicator
`decrease
`further
`hydrolysis
`was
`ysis
`of
`showed
`ing
`that
`free
`form,
`reconstituted
`cyclic
`acid.
`superantant
`urine
`was
`acid
`acid
`lyzer,
`model
`Alto,
`CA).
`cm)
`resin
`(21
`a
`at
`constant
`quired
`for
`mm.
`
`of
`
`urine
`no
`most
`not
`
`the
`
`urine
`pooled
`were
`Samples
`12,
`11 to
`to
`pH
`of
`with
`a beaker
`sample
`ammonia
`performed
`because
`not
`with
`and
`without
`samples
`total
`3-methyihistidine,
`in
`increase
`3-methylhistidine
`in
`human
`peptide
`bound.
`dried
`to
`its
`original
`After
`centrifugation
`and
`was
`decanted
`column
`applied
`to the
`analyzer
`(Beckman
`120
`C,
`Beckman
`3-Methylhistidine
`with
`sodium
`temperature
`run,
`including
`
`analyzed
`also
`were
`alkaline
`made
`dried,
`freeze
`to
`concentration
`Acid
`concentration.
`anal-
`six
`duplicate
`acid
`hydrolysis
`confirm-
`its
`is
`in
`urine
`was
`then
`sample
`The
`with
`7% sulfosali-
`volume
`(15 mm
`at 3000
`x g)
`the
`equivalent
`of
`250i.tl
`an
`automated
`amino
`of
`amino
`ana-
`Spinco
`Instruments,
`Palo
`was
`eluted
`PA-35
`buffer
`0.3 N)
`citrate
`of
`45#{176}C.The
`time
`re-
`regeneration
`was
`235
`
`3-
`
`for
`adding
`by
`placed
`and
`H2SO4
`
`the
`of
`
`acid
`Inc.,
`a
`4.2,
`
`off
`
`(pH
`total
`time,
`
`At
`fusate
`
`various
`were
`
`times
`drawn
`
`during
`off
`and
`
`infusion,
`the
`analyzed
`for
`
`samples
`cystemne
`
`of
`(18).
`
`in-
`
`Eton Ex. 1097
`3 of 10
`
`

`

`CYSTEINE
`
`NEEDS
`
`OF
`
`INTRAVENOUSLY
`
`FED
`
`NEWBORNS
`
`increase
`caused
`but
`had
`taurine,
`or methionine.
`the
`urine
`excretion
`the
`
`917
`
`#{189}
`on
`was
`3-
`
`3.3
`
`urinary
`in
`affect
`no
`cysteine
`Urinary
`statistically
`not
`(contrOl
`=
`0.2
`(cid:1)tmol/kg/24
`
`No
`samples.
`was
`groups
`3.8
`
`=
`
`±
`
`Plasma
`
`amino
`
`acid
`
`response
`
`in
`
`has
`
`taurine
`The
`
`shown
`supplemented
`group.
`were
`plasma
`were
`gen-
`previ-
`value
`low (2).
`samples.
`transient
`origin
`
`in
`
`of
`
`concentration,
`#{189}cystine
`Plasma
`in
`the
`3, was
`greater
`Table
`unsupplemented
`than
`the
`group
`plasma
`methionine
`nor
`Neither
`by
`cysteine
`additions.
`affected
`for methionine
`and
`taurine
`values
`within
`what
`been
`defined
`erally
`as normal
`limits
`the
`#{189}cystine
`but
`ously
`unsupplemented
`group
`may
`be
`in the
`found
`No
`cysteine
`was
`in the
`plasma
`One
`infant
`in each
`group
`developed
`hypermethioninemia
`unknown
`of
`which
`was
`resolved
`the
`termination
`with
`TPN.
`Data
`for
`in
`each
`infant
`one
`suggested
`transient
`hypertaurinemia,
`observation
`may
`have
`been
`plasma
`pipetting
`technique
`sample
`being
`taken
`from
`buffy
`layer
`(26).
`
`group
`but
`this
`faulty
`due
`in
`the
`resulting
`the
`taurine-rich
`
`to
`
`Urinary
`
`amino
`
`acid
`
`response
`
`The
`shown
`
`urinary
`in
`Figure
`
`excretion
`1. Cysteine
`
`of
`
`acids
`amino
`hydrochloride
`
`is
`
`2
`TABLE
`intake
`nutrient
`Actual
`supplemented
`in cysteine
`intravenously
`fed infants*
`
`and
`
`nitrogen
`and
`control
`
`retention
`
`an
`
`and
`
`in
`
`additions
`cystine
`cystathionine
`detected
`methythistidine
`different
`0.2;
`±
`h).
`
`between
`supplemented
`
`Anthropometric
`
`data
`
`not
`=
`
`was
`(control
`= 6.1
`
`between
`different
`change
`Weight
`1.7 g/kg/24
`10.2
`groups
`two
`the
`±
`2.3).
`Similarly,
`there
`supplemented
`h;
`±
`head
`circumference
`in
`were
`no
`differences
`days;
`supplemented
`cm/6
`(control
`0.6
`± 0.1
`=
`change
`(control
`0.9
`0.2)
`or
`length
`±
`=
`0.2
`cm/6
`days;
`supplemented
`0.6
`±
`=
`between
`the
`groups.
`
`=
`
`±
`
`0.6
`0.1)
`
`Effect
`
`of gestation
`
`and
`
`postnatal
`
`age
`
`Postnatal
`ways.
`First,
`mented
`and
`into
`
`those
`
`effect
`age
`shown
`as
`control
`14 days
`
`examined
`was
`in Table
`4,
`groups
`were
`versus
`those
`
`two
`in
`supple-
`the
`subdivided
`older
`than
`
`1
`
`T
`t
`#{176}(cid:1)
`energy
`
`.Nttrogen
`
`Intaket
`
`.
`
`Methzontne
`
`.
`
`Cysteine
`
`.
`
`Taunne
`
`Nitrogen
`
`retentioi4
`
`%
`
`Downloaded from https://academic.oup.com/ajcn/article-abstract/34/5/914/4431066 by Reprints Desk user on 21 May 2020
`
`kcal
`
`mg
`
`87
`
`± 4
`
`508 ±
`
`13
`
`125
`
`±
`
`3
`
`78
`
`±
`
`2
`
`18)
`are
`
`87±4
`
`expressed
`
`as mean
`
`509±15
`± SE/kg/24
`
`h.
`
`127 ±4
`
`0
`
`0
`
`0
`
`mg
`
`280
`
`±
`
`16
`
`283±11
`
`55.7
`
`55.6
`
`infused
`the
`basis,
`Ca
`14 mmol;
`0.048
`(cid:1)smol;
`Cr
`folic
`B12 75 (cid:1)tg;
`a
`10% emulsion.
`intake
`(Aminosyn)
`
`control
`6.5 mmol;
`j(cid:1)mol;
`acid
`
`supplied
`solution
`P 6.0 mmoh;
`Mg
`vitamin
`B,
`0.5 mg;
`vitamin
`
`following:
`the
`Zn
`3.0 mmol;
`mg;
`B2
`10 mg;
`C 650 mg;
`A 5000
`
`100
`Cu
`
`glucose
`14 (cid:1)moh;
`niacinamide
`IU;
`D 500
`
`g; nitrogen
`6.25
`itmol;
`87.5
`mg;
`IU;
`E 5 IU.
`
`27.5
`
`-
`
`nitrogen
`
`loss
`
`(urine
`
`+
`
`stool
`
`+ GI
`
`drainage)
`
`during
`
`3-day
`
`18)
`
`values
`
`Supplemented
`(n =
`Control(n=
`* All
`t When
`g; Na
`3.2
`9.0
`Mn
`pantothenic
`In
`addition
`(cid:1) Nitrogen
`balance
`period.
`
`a per
`on
`expressed
`Cl
`K 15 mmol;
`14 mmol;
`0.38
`(cid:1)tmol;
`Se
`(cid:1)mol;
`I 0.47
`B6
`acid
`18 mg;
`13.5 mg;
`lipid
`was
`provided
`from
`retention
`nitrogen
`
`litre
`
`=
`
`3
`TABLE
`concentration
`amino
`sulfur
`Plasma
`and
`control
`supplemented
`in cysteine
`intravenously
`fed infants* (jLmol!dl)
`
`acid
`
`Supplemented
`Control
`* All
`
`values
`
`are
`
`expressed
`
`as mean
`
`Methionine
`
`±
`±
`
`0.41
`0.43
`
`5.25
`5.16
`± SE.
`
`t Supplemented
`
`greater
`
`than
`
`control,
`
`p <
`
`0.05.
`
`#{189}Cysteine
`
`5.22
`2.98
`
`± 0.43t
`± 0.23
`
`Taurine
`
`0.44
`4.81
`±
`4.42 ± 0.51
`
`Eton Ex. 1097
`4 of 10
`
`(cid:1)
`

`

`U
`
`SLiP(cid:1))
`
`p.(cid:1)O.O5
`
`p(cid:1):OO1
`
`918
`
`ZLOTKIN
`
`ET
`
`AL.
`
`URINARY
`AMINO
`EXCRET
`(mg/kg!
`
`ACID
`ION
`24li
`
`r)
`
`8
`
`7
`
`6
`
`5
`
`4
`
`3
`
`2
`
`1
`
`0
`
`FIG.
`
`1. The
`
`effect
`
`of
`
`intravenous
`
`cysteine
`
`supple-
`
`mentation
`
`on
`
`urinary
`
`sulfur
`
`amino
`
`acid
`
`excretion.
`
`cyst
`
`me
`
`methionine
`
`oVstatj,
`
`j011
`
`j,(cid:1)
`
`taurine
`
`TABLE
`Nitrogen
`cysteine
`infants
`
`4
`retention
`supplemented
`varying
`
`of
`
`Supplemented
`
`Control
`
`and
`
`concentration
`#{189}cystine
`plasma
`and
`control
`intravenously
`postnatal
`and
`gestational
`
`age
`
`in
`
`fed
`
`Postantal
`
`age
`
`n
`
`Nitrogen
`
`retention’
`
`Plasma
`
`#{189}cystinet
`
`days
`
`nig/kg/24
`
`h
`
`gunol/di
`
`20(cid:1)
`±
`± 29
`18
`±
`13
`±
`
`0.4
`5.07 ±
`1.2
`5.56 ±
`2.96
`± 0.5
`3.0
`± 0.7
`
`Downloaded from https://academic.oup.com/ajcn/article-abstract/34/5/914/4431066 by Reprints Desk user on 21 May 2020
`
`283
`271
`293
`272
`
`Nitrogen
`
`retention
`
`mg/kg/24
`
`h
`
`283
`290
`296
`304
`loss
`
`22
`28
`22
`18
`
`±
`±
`±
`±
`(urine
`
`Plasma
`
`#{189}cysttne
`
`pmol/dI
`
`0.6
`5.08
`±
`4.82
`± 0.7
`3.53
`± 0.7
`0.7
`3.03 ±
`drainage)
`during
`
`3-day
`
`+
`
`stool
`
`+ GI
`
`12
`6
`10
`8
`
`n
`
`7 8
`
`7 8
`
`(Aminosyn)
`
`-
`
`nitrogen
`
`(cid:1)l4
`(cid:1)l4
`(cid:1)14
`(cid:1)l4
`
`Gestation
`
`age
`
`wk
`
`(cid:1)32
`(cid:18)37
`(cid:1)32
`(cid:1)37
`intake
`
`Supplemented
`
`Control
`
`* Nitrogen
`
`retention
`
`=
`
`nitrogen
`
`balance
`t Blood
`j Mean
`
`period.
`sample
`± SEM.
`
`drawn
`
`at
`
`end
`
`of
`
`3-day
`
`balance
`
`period,
`
`between
`
`0900
`
`and
`
`1100
`
`h.
`
`14 days
`14
`plasma
`age.
`
`were
`infants
`
`regression
`by
`and
`Neither
`nitrogen
`days.
`#{189}cystine
`affected
`Second,
`eight
`who
`
`of
`
`those
`nor
`
`analysis
`retention
`by
`postnatal
`received
`TPN
`
`during
`Cysteine
`increase
`(mean
`
`life were
`of
`1st wk
`the
`was
`supplementation
`plasma
`#{189}cystine
`increase
`2.29
`±
`
`=
`
`0.5
`
`matched.
`pair
`found
`again
`concentration
`(cid:1)smo1/d1;
`
`p
`
`to
`
`<
`
`Eton Ex. 1097
`5 of 10
`
`(cid:1)
`

`

`CYSTEINE
`
`NEEDS
`
`OF
`
`INTRAVENOUSLY
`
`FED
`
`NEWBORNS
`
`919
`
`N retention
`affect
`not
`but
`0.05)
`h;
`supplemented
`mg/kg/24
`±32
`249
`12.7).
`Gestational
`SE(cid:1)
`1 1.0;
`47; A =
`±
`=
`by
`comparing
`examined
`effects
`were
`versus
`full
`term
`gestation
`32 wk
`of
`analysis
`all
`infants.
`and
`by
`regression
`not
`influence
`N retention
`tational
`age
`did
`#{189}cystine
`concentration.
`
`(control
`=
`
`=
`260
`age
`infants
`infants
`Ges-
`or
`
`of
`
`of
`
`cysteine
`
`supplementation
`
`in matched
`
`Effect
`pairs
`
`Clinical
`
`outcome
`
`of
`
`the
`not
`either
`other
`
`death
`to
`
`The
`sequent
`could
`riod
`of
`susion
`the
`All
`of
`the
`neonatal
`home
`or
`obvious
`tween
`
`the
`
`three
`completion
`be
`directly
`parenteral
`were
`infants
`care
`intensive
`the
`referring
`to
`differences
`in
`two
`groups.
`
`premature
`their
`of
`related
`nutrition
`discharged
`their
`unit
`to
`with
`hosptial
`clinical
`outcome
`
`sub-
`pe-
`in-
`
`infants
`study
`to
`the
`regimen.
`from
`own
`no
`be-
`
`group
`
`the
`
`t
`
`Pairs
`
`by
`less
`
`analysis
`the
`to
`addition
`In
`statistical
`strengthen
`to further
`order
`from
`24
`results,
`subjects
`of
`our
`ysis
`matched
`were
`paired
`periods
`study
`test.
`by
`paired
`analyzed
`data
`cysteine
`those
`infants,
`as
`defined
`energy
`and
`control,
`with
`and
`mented
`than
`10%;
`differing
`less
`intakes
`differing
`than
`1 wk;
`ages
`ages
`32
`tional
`of
`results
`weight
`tion,
`and
`tion,
`presented
`are
`67% increase
`a
`significant
`increase
`cretion.
`Weight
`plasma
`methionine,
`tion
`no
`different
`fants
`in
`their
`matched
`
`were
`and
`
`in
`
`and
`anal-
`of
`the
`and
`the
`were
`supple-
`nitrogen
`postnatal
`and
`gesta-
`by
`37 wk.
`The
`or
`either
`nitrogen
`reten-
`for
`pair
`matching
`change,
`3-methylhistidene
`excre-
`acid
`plasma
`sulfur
`amino
`response
`test
`in Table
`5. Paired
`showed
`t
`#{189}cystine
`in
`plasma
`and
`in
`3-methythistidine
`retention,
`change,
`nitrogen
`concentra-
`and
`taurine
`supplemented
`controls.
`
`Biochemical
`
`changes
`
`of
`
`the
`
`following
`parameters
`cysteine
`hematocrit,
`Ca,
`P,
`and
`
`biochemical
`were
`affected
`supplementation:
`platelet
`count,
`acid-base
`status.
`
`Na,
`
`and
`by
`he-
`K,
`
`in
`
`Discussion
`
`results
`that
`
`our
`
`acid
`
`investigation
`cys-
`of
`effect
`alter
`
`no
`has
`but may
`intravenously
`
`in
`
`present
`of
`The
`supplementation
`cysteine
`suggest
`mixtures
`amino
`teine-free
`or growth,
`balance
`on
`nitrogen
`metabolism
`muscle
`protein
`infants.
`fed
`newborn
`the
`that
`The
`observation
`retention
`differ
`in nitrogen
`not
`was
`that
`this measurement
`mean
`of
`to
`detect
`the
`effect
`enough
`been
`However,
`it has
`(27).
`tons
`nitrogen
`balance
`favorable
`less
`as 48 h after
`the
`exclusion
`early
`acid
`from
`an
`infant’s
`amino
`study
`we
`incorporated
`present
`by
`h
`72
`followed
`time
`design
`Although
`this
`period.
`to detect
`to
`be
`adequate
`pected
`which
`cannot
`an
`amino
`acid
`ity
`of
`in
`the
`body,
`to
`any
`extent
`sized
`cysteine
`of
`a
`low
`level
`that
`cysteine
`with
`stored
`bined
`or
`bound
`to
`proteins
`meet
`cysteine
`requirements
`thesis
`and N balance
`over
`
`groups
`two
`(Table
`not
`cysteine
`shown
`is detected
`of
`an essential
`diet
`(28).
`In
`an
`adaptation
`72-h
`balance
`might
`be
`the
`essential-
`be
`synthe-
`is possible
`it
`synthesis
`com-
`as glutathione
`(29)
`was
`sufficient
`to
`for
`protein
`syn-
`duration
`the
`
`a
`
`the
`
`did
`2) may
`sensitive
`addi-
`that
`
`a
`as
`
`the
`
`ex-
`
`of
`
`of
`
`(30)
`
`a
`ex-
`
`in-
`
`Downloaded from https://academic.oup.com/ajcn/article-abstract/34/5/914/4431066 by Reprints Desk user on 21 May 2020
`
`Taurine
`
`±
`
`±
`
`1.85
`
`1.24
`
`7.04
`
`6.58
`
`0.09
`6.67
`NS
`
`None
`hematological
`the
`parenteral
`moglobin,
`Cl, BUN,
`
`TABLE
`Effect
`
`5
`cysteine
`
`of
`
`Supplemented
`(n=
`12)
`Control
`(n=
`
`12)
`
`SE(cid:1)
`Significancet
`* Group
`
`t By
`
`paired
`
`t
`
`test.
`
`supplementation
`
`in pair-matched
`
`patients
`
`Nitrogen
`
`retention
`
`wt
`
`cisange
`
`3-Methyihisti-
`dine
`excretion
`
`Methionine
`
`mg/kg/24
`
`Is
`
`g/kg/24
`
`h
`
`(cid:1)unol/kg/24
`
`h
`
`Plasma
`
`#{189}Cystine
`
`pjnol/dl
`
`287.7
`
`± 20.0*
`
`6.8
`
`± 3.2
`
`3.6
`
`± 0.2
`
`5.13 ± 0.2
`
`5.48 ± .58
`
`294.3
`
`±
`
`10.1*
`
`9.1
`
`±
`
`1.7
`
`3.1 ± 0.2
`
`5.34 ± 48.0
`
`3.28 ±
`
`.57
`
`-6.67
`21.35
`NS
`
`mean
`
`±
`
`SEM.
`
`-2.30
`2.81
`NS
`
`0.51
`0.23
`<0.05
`
`-0.30
`0.60
`NS
`
`2.32
`0.89
`<0.05
`
`Eton Ex. 1097
`6 of 10
`
`(cid:1)
`(cid:1)
`(cid:18)
`(cid:1)
`

`

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`
`920
`
`ZLOTKIN
`
`ET
`
`AL.
`
`This
`
`study.
`through
`by
`using
`to measure
`
`only
`can
`possibility
`studies
`longer
`term
`more
`sophisticated
`rates
`ofwhole
`body
`
`be
`and
`tech-
`protein
`
`present
`explored
`possibly
`niques
`synthesis.
`to
`of N balance
`failure
`the
`Although
`supplementation
`appears
`spond
`to cysteine
`view
`that
`cysteine
`is an
`essen-
`contradict
`the
`for
`newborns
`10)
`the
`pre-
`tial
`amino
`acid
`(9,
`should
`be
`There
`vious
`evidence
`reexamined.
`one
`reported
`study
`has
`been
`only
`clinical
`associated
`growth
`one
`infant
`which
`decreased
`with
`and
`nitrogen
`retention
`the
`exclusion
`artificial
`cysteine
`from
`oral
`formula
`clinical
`Methodological
`and
`details
`from
`this
`reported
`never
`been
`study.
`convers-
`and
`adults,
`children
`In
`older
`the
`fmally
`to
`cysteine
`sion
`of methionine
`and
`the
`in
`by
`enzymes
`taurine
`and
`sulfate
`In
`(9).
`and
`kidney
`(32)
`is well
`accepted
`the metabolism
`trast,
`little
`was
`known
`about
`relatively
`of
`cysteine
`in
`newborns
`until
`that
`all
`cently.
`In
`1970
`it was
`reported
`enzymes
`transsulfuration
`pathway
`adult
`to
`low
`activity
`compared
`enzyme
`the
`more
`importantly
`that
`cystathionine
`nase,
`which
`converts
`fetal
`liver
`was
`absent
`in
`the
`the
`recent
`in
`often
`overlooked
`showing
`that
`subsequent
`report
`trimester
`has
`ney
`by the
`second
`thirds
`the
`cystathionase
`activity
`controls
`(11).
`Furthermore,
`hepatic
`onase
`activity
`in
`premature
`and
`newborns
`matures
`very
`quickly
`after
`that
`by
`9 days
`age
`in
`the
`premature
`in
`about
`3 days
`the
`full
`term,
`70% of
`been
`activity
`has
`achieved
`(11).
`Thus
`also
`data
`might
`interpreted
`to suggest
`be
`given
`adequate
`methionine,
`even
`the
`ture
`can
`produce
`sufficient
`cysteine
`its
`requirements
`for
`protein
`synthesis.
`Presently,
`infant
`formulas
`all
`elemental
`formulas)
`contain
`the
`quantities
`cysteine.
`Unlike
`mulas,
`neither
`protein
`nor most
`amino
`acid
`formulations
`contain
`more
`amounts
`Despite
`the
`cysteine
`intravenous
`mulations,
`infants
`are
`adequate
`of
`nitrogen
`cellent
`retention
`
`re-
`to
`
`of
`
`of
`(31).
`have
`
`to
`liver
`con-
`
`re-
`the
`of
`showed
`values
`and
`cystathio-
`to cysteine
`However,
`(9).
`is a
`literature
`kid-
`the
`fetal
`two-
`achieved
`of mature
`cystathi-
`full
`term
`birth
`so
`and
`adult
`these
`that,
`prema-
`to meet
`
`for-
`
`(including
`considerable
`the
`oral
`hydrolysates
`intravenous
`than
`trace
`exclusion
`of
`feeding
`for-
`provided
`with
`and
`energy,
`ex-
`growth
`is ob-
`
`and
`
`of
`
`of
`however,
`crystalline
`(33),
`cysteine.
`of
`these
`from
`when
`intakes
`nitrogen
`
`to
`
`that
`
`do
`
`the
`
`of
`
`not
`
`N reten-
`study,
`present
`the
`In
`24).
`(23,
`served
`the
`cysteine-free
`with
`infused
`infants
`of
`tion
`expected
`in utero
`that
`similar
`was
`solution
`of
`exogenous
`exclusion
`the
`if
`Therefore
`(25).
`on
`the
`intra-
`effect
`a metabolic
`has
`cysteine
`was
`more
`effect
`infant,
`fed
`venously
`by N retention.
`measured
`that
`than
`subtle
`parenteral
`nutrition
`receive
`infants
`Few
`after
`birth,
`and
`those
`5 to 7 days
`than
`earlier
`the
`“sickest”
`new-
`by
`definition
`are
`that
`the
`investigation
`aver-
`present
`In
`borns.
`studied
`the
`infants
`was
`age
`postnatal
`age
`argued
`that
`could
`be
`the
`therefore
`15 days.
`It
`whether
`or
`establish
`not
`do
`data
`derived
`age. However,
`before
`cysteine
`is required
`less
`than
`those
`analysis
`of
`only
`unsupple-
`days
`age
`(supplemented
`between
`relation
`mented)
`revealed
`no
`and
`nitrogen
`infants
`of
`postnatal
`age
`the
`#{189}cystine.
`Similar
`results
`retention
`or
`plasma
`vulnerable
`to
`from
`those
`infants
`most
`that
`those
`potential
`cysteine
`deficiency,
`life,
`further
`of
`alimented
`during
`the
`1st wk
`cysteine
`supple-
`support
`observation
`that
`mentation
`does
`not
`nitrogen
`balance
`intravenously
`fed
`Therefore,
`though
`results
`directly
`to
`only
`sickest
`it
`reasonable
`to
`suggest
`cysteine
`mentation
`would
`not
`nitrogen
`tion
`in
`normal
`newborns.
`3-methythistidine
`the
`present
`study
`In
`0.05)
`an
`average
`increased
`(p
`cretion
`<
`pair-matched
`the
`in
`(cid:1)tmo1/kg/day
`This
`represents
`infants.
`supplemented
`of 300 mg
`of muscle
`creased
`breakdown
`day
`in
`the
`supplemented
`per
`tein
`infant
`neonatal
`muscle
`contains
`group
`because
`/Lmol
`of
`3-methythistidine/g
`protein
`of
`However,
`an
`explanation
`relationship
`this
`between
`cysteine
`supplementation
`and
`small
`increase
`3-methythistidine
`excretion
`in
`is not
`readily
`apparent.
`The
`factors
`regulating
`muscle
`protein
`catabolism
`are
`complex
`unknown
`in
`neonate.
`Since
`nitrogen
`the
`tention
`was
`similar
`in
`two
`groups,
`increase
`in
`3-methythistidine
`excretion
`of
`have
`resulted
`from
`one
`possible
`two
`have
`cesses.
`First,
`it may
`arisen
`from
`increase
`in protein
`catabolism
`with
`or without
`a net
`decrease
`in muscle
`protein
`mass.
`Sec-
`ond,
`it may
`have
`represented
`change
`in
`protein
`turnover
`rate,
`but
`increase
`in
`
`of
`
`only
`
`our
`
`our
`the
`
`per
`
`14
`
`the
`
`a
`
`of
`al-
`
`is
`
`seems
`
`applied
`very
`supple-
`reten-
`
`ex-
`of 0.5
`cysteine
`an
`
`in-
`pro-
`
`1.7
`(34).
`
`and
`re-
`an
`may
`pro-
`an
`
`that
`infants
`
`and
`
`alter
`infants.
`be
`can
`newborns,
`that
`improve
`
`of
`the
`
`the
`
`no
`net
`
`a
`
`Eton Ex. 1097
`7 of 10
`
`

`

`CYSTEINE
`
`NEEDS
`
`OF
`
`INTRAVENOUSLY
`
`FED
`
`NEWBORNS
`
`921
`
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`
`of
`excretion
`sug-
`increased,
`increase
`activity
`to
`taurine.
`The
`high
`in
`human
`milk
`that
`enzyme
`increased
`There-
`despite
`feed-
`syn-
`in
`
`little
`fed
`life,
`
`of
`
`those
`
`the
`
`of
`found
`suggestion
`to
`produce
`conditions.
`that
`surprising
`in all
`intravenous
`taurine
`deficiency
`described.
`Possibly
`converting
`methio-
`to actively
`con-
`is present.
`Conser-
`taurine
`has
`been
`de-
`infants
`ingesting
`artificial
`contain
`very
`taurine
`weight
`infants
`human
`of
`the
`first
`3 wk
`taurine
`acids
`predominated,
`while
`formula,
`concentrations
`were
`found
`to exceed
`12th
`day.
`The
`predominance
`conjugates
`may
`reflect
`of
`endogenous
`taurine.
`bile
`pro-
`investigation,
`acid
`in fact,
`studied
`and
`few stools
`these
`intravenously
`fed
`in-
`speculate,
`however,
`that
`in
`fed
`infants
`without
`oral
`losses
`(through
`stool)
`and
`would
`be
`considerably
`to
`orally
`fed
`infants.
`does
`not
`answer
`the
`of
`taurine
`synthesis
`a
`cysteine-free
`oral
`
`ofbile
`on
`fed
`conjugates
`by the
`bile
`acid
`conservation
`the
`present
`was
`not
`passed
`by
`One
`could
`intravenously
`bile
`acid
`requirements
`compared
`this
`study
`the
`adequacy
`were
`fed
`
`of
`infants
`
`urinary
`However,
`cysteine.
`nous
`#{189}cystine
`taurine
`and
`both
`enzyme
`sufficient
`gesting
`synthesis
`endogenous
`concentration
`taurine
`this
`supports
`44)
`(43,
`is
`sufficient
`capacity
`under
`appropriate
`taurine
`is perhaps
`not
`it
`fore,
`absence
`of
`taurine
`the
`a
`formulations,
`ing
`been
`has
`not
`drome
`to mechanisms
`addition
`to taurine,
`a mechanism
`nine
`endogenous
`taurine
`serve
`of
`endogenous
`vation
`in orally
`fed
`scribed
`formulations
`which
`low
`(45).
`In
`birth
`milk
`throughout
`conjugation
`in
`those
`glycine
`oftaurine
`ofglycine
`active
`In
`duction
`were
`fants.
`totally
`intake,
`taurine
`decreased
`Therefore,
`question
`if
`the
`formula.
`Various
`priate
`intake
`the
`newborn
`(46,
`47).
`The
`acid
`requirement
`g of
`protein
`based
`2 g of
`protein/kg/24
`of
`similar
`N retention
`acid
`intakes
`of 40 mg/g
`onine)
`versus
`64 mg/g
`onine
`plus
`cysteine)
`quirement
`for
`total
`infants
`studied
`has
`of protein.
`Another
`
`suggestions
`of
`total
`infant
`present
`for
`on
`
`the
`
`appro-
`regarding
`acids
`for
`sulfur
`amino
`forward
`have
`been
`put
`amino
`estimated
`sulfur
`the
`newborn
`is 29 mg/
`a safe
`level
`intake
`of
`of
`h (48).
`The
`observation
`at
`total
`sulfur
`amino
`of protein
`(as methi-
`of
`protein
`(as methi-
`suggested
`that
`the
`re-
`sulfur
`amino
`acids
`in
`the
`been
`satisfied
`at 40 mg/g
`
`factor
`
`possibly
`
`influencing
`
`our
`
`re-
`
`muscle
`tion
`ify
`
`Further
`isotopes
`
`metabolic
`are
`required
`
`investiga-
`to clar-
`
`protein.
`using
`stable
`this
`response.
`by
`unanswered
`question
`An
`additional
`to
`the metabolic
`results
`relates
`experimental
`has
`been
`It
`infused
`cysteine.
`fate
`of
`the
`intravenous
`the
`infusion
`of
`ported
`that
`cysteine
`to normal
`tions
`containing
`plasma
`cysteine
`unteers
`increased
`#{189}cystine
`plasma
`while
`affect