Journal of Pediatric Gastroenterology and Nutrition
`3:239-244 © 1984 Raven Press, New York
`
`Total Parenteral Nutrition in Sick Preterm Infants: Effects
`of Cysteine Supplementation with Nitrogen Intakes
`of 240 and 400 mg/kg/day
`
`Michael H. Malloy, David K. Rassin, and C. Joan Richardson
`
`Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas
`
`Summary: The effects of supplementing total parenteral
`nutrition (TPN) solutions with cysteine were assessed at
`two different levels of nitrogen intake by determining ni(cid:173)
`trogen retention, sulfate excretion, and sulfur-containing
`amino acid concentrations. Ten infants received 72 mg/
`kg/day of cysteinesHCl in a TPN solution for a period of
`6 days. Fiv.e of these infants received 251 ± 48 (x ± SD)
`mg/kg/day of nitrogen, and five received 403 ± 4S-mg/
`kg/day of nitrogen. Two other groups of five infants each
`received unsupplemented TPN at nitrogen intakes of 235
`± 48 and 412 ± 54 mg/kg/day, respectively. Fluid and
`
`nonprotein caloric intakes were similar for all four
`groups. Cysteine supplementation increased plasma and
`urine free cyst(e)ine concentrations and enhanced total
`sulfur retention, but did not enhance nitrogen retention.
`[Cyst(e)ine refers to the mixture in any proportion of the
`sulfhydryl (cysteine) and the disulfide (cystine) forms of
`this compound.] Nitrogen retention, sulfate excretion,
`cyst(e)ine excretion, and plasma taurine concentrations
`increased as the result of the increase in nitrogen intake.
`Key Words: Cysteine-Total parenteral nutrition-In(cid:173)
`fants.
`
`Total parenteral nutrition (TPN) is an effective
`means of nourishing infants who are unable to be
`fed enterally. It is used to sustain infants until en(cid:173)
`teral nutrition is fully established or as a means of
`providing adequate calories and nitrogen to pro(cid:173)
`mote growth (1-3). The developing metabolic ca(cid:173)
`pabilities of infants, however, make the require(cid:173)
`ments for individual components of parenteral nu(cid:173)
`trition regimens uncertain.
`Gaull et al. (4) observed that hepatic cysta(cid:173)
`thionase, the rate-limiting enzyme in the production
`of cysteine from methionine, was virtually absent in
`second-trimester human fetuses, but that enzyme
`activity increased with gestational age. Thus, cys(cid:173)
`teine may be essential for the preterm and newly
`born term infant. As preterm and term infants in(cid:173)
`crease in postnatal age, however, hepatic cysta(cid:173)
`thionase activity increases rapidly (5). From a de(cid:173)
`velopmental standpoint the enzymatic mechanism
`for the synthesis of cysteine from methionine ap-
`
`Address correspondence and reprint requests to Dr. Malloy
`at Department of Pediatrics, University of Texas Medical
`Branch, Galveston, Texas 77550.
`
`pears to be in place, but in an evolving state at
`birth, for both preterm and term infants. Whether
`or not an exogenous source of cysteine is required
`during TPN in infancy has not been resolved on the
`basis of developmental biochemical data.
`Several studies have attempted to document clin(cid:173)
`ically the need for an exogenous source of cysteine
`during infancy. The data most frequently cited in
`support of a cysteine requirement come from a re(cid:173)
`port by Snyderman (6) that documents impaired ni(cid:173)
`trogen retention and weight gain in infants in the
`absence of an enteral source of cysteine. Pohlandt
`(7) attempted to demonstrate the need for an ex(cid:173)
`ogenous source of cysteine during TPN in an indi(cid:173)
`rect manner by documenting that plasma concen(cid:173)
`trations of half-cystine did not increase in infants
`receiving TPN when an adequate source of methi(cid:173)
`onine was provided. Recently, Zlotkin et al. (8) cast
`doubt on the essential nature of cysteine when they
`observed that infants receiving cysteine-supple(cid:173)
`mented TPN failed to retain nitrogen and gain
`weight better than infants who received unsupple(cid:173)
`mented TPN.
`In the sick preterm infant during the first weeks
`
`239
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`240
`
`M. H. MALLOY ET AL.
`
`of life it is difficult to provide caloric intakes much
`greater than 60 kcal/kg/day by peripheral intrave(cid:173)
`nous administration. ·At this relatively low caloric
`intake, however, nitrogen retention has been dem(cid:173)
`onstrated with a nitrogen intake of 400 mg/kg/day
`(3). This caloric intake has also been shown to meet
`the total energy expenditure of infants in a ther(cid:173)
`moneutral environment (9,10). The effects of sup(cid:173)
`plementing TPN solutions with cysteine at 60 kcal/
`kg/day and 400 mg/kg/day of nitrogen have not been
`evaluated. Nor has the effect of supplementing TPN
`solutions with cysteine at a lower level of nitrogen
`intake been determined. We report here the effects
`of cysteine supplementation at nitrogen intakes of
`240 and 400 mg/kg/day with a nonprotein caloric
`intake of 60-70 kcal/kg/day.
`
`PATIENTS AND METHODS
`
`Infants were enrolled in the study protocol if they
`were at least 2 days old, unable to take enteral
`feeds, and unlikely to begin enteral feeding within
`5-7 days; or if they had been without any enteral
`intake for 48 h and would be unable to tolerate en(cid:173)
`teral feeds for at least 5-7 days. Of the 20 infants
`enrolled in the study, 16 had a primary diagnosis of
`
`respiratory distress syndrome, 3 had a primary di(cid:173)
`agnosis of necrotizing enterocolitis, and 1 had gas(cid:173)
`troschisis. Clinical information concerning the char(cid:173)
`acteristics of the infants enrolled in the study is
`given in Table 1.
`After obtaining parental permission to enroll an
`infant in the study protocol, the infant was begun
`on the supplemented or unsupplemented TPN reg(cid:173)
`imen that had been selected randomly. Infants in
`the low nitrogen intake groups (Group 1, unsupple(cid:173)
`mented; Group 2, cysteine-supplemented) received
`150 ml/kg/day of fluid, 60 kcal/kg/day of glucose, and
`240 mg/kg/day of nitrogen (Aminosyn, Abbott Lab(cid:173)
`oratories, Abbott Park, Chicago, IL). The only
`sulfur-containing amino acid in Aminosyn is methi(cid:173)
`onine. Infants in the high nitrogen intake groups
`(Group 3, unsupplemented; Group 4, cysteine-sup(cid:173)
`plemented) received the same nonprotein caloric
`and fluid intakes as the low nitrogen groups but
`were given 400 mg/kg/day of nitrogen. The infants
`in the two groups receiving cysteine supplementa(cid:173)
`tion were given 72 mg/kg/day of cysteine-HCl (Ab(cid:173)
`bott) added to the TPN solution. The other com(cid:173)
`ponents of the TPN solution are listed in Table 2.
`During the course of the 6-day period of TPN none
`of the infants received any enteral nutrition. No in-
`
`TABLE 1. Characteristics of infants studieda
`
`Low nitrogen
`intake
`
`High nitrogen
`intake
`
`Group 1
`TPN
`n = 5
`
`Group 2
`TPN + CYSE
`n = 5
`
`Group 3
`TPN
`n = 5
`
`Group 4
`TPN + CYSE
`n = 5
`
`1.46
`(900-2300)
`
`1.37
`(910-2500)
`
`1.25
`(970-1510)
`
`1.01
`(890-1150)
`
`4
`(3-5)
`
`7
`(4-11)
`
`20
`(3-53)
`
`5
`(4-5)
`
`158 ± 16
`
`133 ± 30
`
`158 ± 16
`
`157 ± 43
`
`63 ± 13
`
`63 ± 5
`
`73 ± II
`
`67 ± 8
`
`235 ± 48
`
`251 ± 48
`
`412 ± 54
`
`403 ± 45
`
`0
`
`72
`
`0
`
`72
`
`-59
`( -160 to 40)
`
`+6
`(-40 to 60)
`
`-12
`( -90 to 60)
`
`-14
`(-80 to 20)
`
`Characteristic
`
`Birthweight (kg)
`
`Age enrolled
`(days)
`
`Fluid intake
`(ml/kg/day)
`Nonprotein
`calories
`(kcal/kg/day)
`Nitrogen intake
`(mg/kg/day)
`Cysteine intake
`(mg/kg/day)
`Weight change per
`6-day study
`period (g)
`
`Abbreviations used: TPN, total parenteral nutrition; CYSE, cysteine.
`a Values are means ± SD, or range.
`
`J Pediatr Gastroenterol Nutr, Vol. 3, No. 2, 1984
`
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`CYSTEINE-SUPPLEMENTED TOTAL PARENTERAL NUTRITION
`
`241
`
`TABLE 2. Parenteral nutrition solution components
`
`Component
`
`Quantity per day
`
`Amino acids"
`Glucose
`Sodium chloride
`Potassium chloride
`Calcium gluconate
`Magnesium sulfate
`Multivitamin concentrateh
`Zinc
`Copper
`
`240 or 400 mg/kg nitrogen
`15 g/kg
`2-6 mEq/kg
`2~3 mEq/kg
`0.9 mEq/kg
`0.25 mEq/kg
`1.0 ml/kg
`300 µ,g/kg
`20 µ,g/kg
`
`• Amino acids provided by Aminosyn (Abbott Laboratories,
`Abbott Park, Chicago, IL). In grams per 100 g amino acids:
`isoleucine, 7.3; Jeucine, 9.5; lysine, 7.3; methionine, 4.0; phe(cid:173)
`nylalanine, 4.4; threonine, 5.3; tryptophan, 1.7; valine, 8.0; ty(cid:173)
`rosine, 0.6; alanine , 12.9; arginine , 10.0; histidine , 3.0; proline,
`8.8; serine, 4.3; glycine, 12.9.
`b Multivitamin concentrate (USV Pharmaceutical, New York,
`NY). Each 5-cc vial contained ascorbic acid, 500 mg; vitamin
`A, 10,000 USP units; vitamin D, 1,000 USP units; thiamine, 50
`mg; riboflavin, 10 mg; niacinamide, 100 mg; pyridoxine-HCl, 15
`mg; despanthenol, 25 mg; d/-a-tocopheryl acetate, 5 IU .
`
`travenous fat emulsions were used during the study
`period, because the majority of infants were still in
`the acute phase of respiratory disease and were on
`ventilators and many had bilirubin concentrations
`in the 6-10 mg/dl range.
`Throughout the 6-day period all infants were
`maintained on radiant warmers. The infants were
`weighed daily, and fluid intake and urinary output
`were accurately recorded hourly. Total parenteral
`nutrition solutions were administered through pe(cid:173)
`ripheral intravenous lines by continuous infusion
`delivered by IVAC pumps (IVAC Corporation, San
`Diego, CA). Laboratory measurements of serum
`electrolytes, blood urea nitrogen, plasma ammonia,
`serum alanine aminotransferase, serum aspartate
`aminotransferase, and hemoglobin were made
`during the 6-day period at the discretion of the pri(cid:173)
`mary physician and not as part of the study. On day
`6 of the study a 24-h urine collection was begun.
`Urine was collected in adherent plastic bags at(cid:173)
`tached to the infants' perineum. Urine that leaked
`from the bag was recorded by weighing the diaper.
`Urine was collected from the bag hourly and frozen
`in a plastic container. No stool or significant gastric
`drainage was recorded during any of the collection
`periods. Blood was collected in a heparinized sy(cid:173)
`ringe through an umbilical artery catheter or by pe(cid:173)
`ripheral venipuncture at least 12 h into the 24-h
`urine collection. The blood was taken immediately
`to the laboratory on ice, and the red blood cells
`separated from the plasma by centrifugation at
`
`1,000 x g in a Beckman microcentrifuge (Beckman
`Instruments, Palo Alto, CA). The plasma was de(cid:173)
`canted from the red blood cells, and the plasma
`proteins were precipitated with a 3% sulfosalitylic
`acid solution (1: 3, volume/volume). After centrifu(cid:173)
`gation at 17,000 xg for 10 min the supernatant so(cid:173)
`lution was decanted and frozen at - 20°C until time
`of analysis.
`Plasma and urine amino acid concentrations were
`measured with a Beckman 119 CL amino acid an(cid:173)
`alyzer; free cyst(e)ine was measured by the method
`of Gaitonde (11) as modified by Malloy et al. (12).
`[Cyst(e)ip.e refers to the mixture in any proportion
`of the sulfhydryl (cysteine) and the disulfide (cys(cid:173)
`tine) forms· of this compound.] Urine sulfate was
`measured by the method of Jackson and Mc(cid:173)
`Candless (13). Total nitrogen in the urine was de(cid:173)
`termined by Kjeldahl analysis, and nitrogen reten(cid:173)
`tion was calculated as nitrogen intake minus 24-h
`urine nitrogen output. Nitrogen intake was calcu(cid:173)
`lated on the basis of each 100 g of Amino syn being
`composed of 16% nitrogen.
`Analysis of the nitrogen retention, sulfate excre(cid:173)
`tion, plasma sulfur-containing amino acid, and urine
`sulfur-containing amino acid data was performed by
`two-way analysis of variance. For each variable
`measured the effect of cysteine supplementation or
`lack of supplementation, the effect of high or low
`nitrogen intake, and the interaction of cysteine and
`nitrogen intake were determined. The level of a sig(cid:173)
`nificant effect was set at a p value of <0.05 . Sig(cid:173)
`nificant differences between plasma amino acid
`concentrations at the low and high nitrogen intakes
`were determined by the Mann-Whitney test.
`
`RESULTS
`
`The addition of cysteine to TPN solutions did not
`cause the infants to gain weight more rapidly. The
`caloric intake of all the groups was low, and gains
`in weight were the exception (Table 1). Of the
`sulfur-containing amino acid concentrations mea(cid:173)
`sured in the plasma, cysteine supplementation had
`a significant effect only on free cyst(e)ine (p <
`0.0001) (Table 3). The concentration of half-cystine
`bound to plasma proteins was not affected by cys(cid:173)
`teine supplementation. Neither sulfate excretion
`nor nitrogen retention was affected by the addition
`of cysteine. Infants receiving cysteine supplemen(cid:173)
`tation did have significant increases in urine
`cyst(e)ine concentrations (p < 0.0001). Cysteine in(cid:173)
`take had no significant effect on the remainder of
`
`J Pediatr Gastroenterol Nutr, Vol. 3, No . 2, 1984
`
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`242
`
`M. H. MALLOY ET AL.
`
`TABLE 3. Effect of cysteine and nitrogen intake on sulfur-containing amino acid levels, nitrogen retention,
`and sulfate excretiona
`
`Amino acid,
`sulfate, or
`nitrogen
`
`Plasma concentration
`(µ.mol/dl)
`Methionine
`Cystathionine
`Free cyst(e)ine
`Bound half-cystine
`Total cyst(e)ine
`Taurine
`Urine concentration
`(µ.mol/dl)
`Methionine
`Cystathionine
`Free cyst( e )ine
`Taurine
`Sulfate excretion
`(mg/kg/day)
`Nitrogen retention
`(mg/kg/day)
`
`Group 1
`
`Group 2
`
`Group 3
`
`Group 4
`
`Cysteine Nitrogen
`effect
`effect
`p value
`p value
`
`Cysteine
`nitrogen
`interaction
`p value
`
`2.38 ± 0.66
`0.12 ± 0.27
`4.46 ± 1.13
`7.40 ± 3.20
`11.9 ± 3.7
`4.12 ± 1.99
`
`2.84 ± 2.31
`0.32 ± 0.44
`11.34 ± 3.38
`7.90 ± 2.80
`19.2 ± 5.9
`2.36 ± 1.34
`
`3.94 ± 2.19
`0.44 ± 0.87
`4.20 ± 1.34
`4.20 ± 2.10
`8.4 ± 3.1
`5.96 ± 3.89
`
`3.0 ± 3.4
`0.0
`14.48 ± 3.83
`5.40 ± 2.40
`19.9 ± 6.0
`11.22 ± 7.07
`
`0.8221
`0.6054
`0.0001
`0.2500
`0.0005
`0 . .3664
`
`8.14 ± 2.29
`0.74 ± 0.70
`8.64 ± 2.66
`24.00 ± 15.85
`
`0.10 ± 0.22
`1.40 ± 2.55
`47.16 ± 23.75
`23.82 ± 27.04
`
`3.54 ± 3.5
`6.40 ± 5.99
`22.02 ± 17.9
`42.46 ± 47.92
`
`0.0
`2.08 ± 1.06
`83.70 ± 21.83
`43.7 ± 40.58
`
`0.0001
`0.2349
`0.0001
`0.9715
`
`0.4249
`1.0000
`0.2509
`0.0251
`0.2250
`0.0118
`
`0.0233
`0.0483
`0.0082
`0.2386
`
`15.84 ± 9.63
`
`21.22 ± 10.49
`
`52.48 ± 13.52
`
`59.08 ± 10.61
`
`0.2260
`
`0.0001
`
`114.00 ± 20.05
`
`150.20 ± 61.98 229.80 ± 34.24 291.60 ± 35.74
`
`0.4552
`
`0.001
`
`0.5146
`0.1790
`0.1787
`0.1376
`0.1115
`0.0807
`
`0.0288
`0.1125
`0. 1808
`0.9625
`
`0.8996
`
`0.2425
`
`a Values are means ± SD.
`
`the plasma or urine amino acid concentrations mea(cid:173)
`sured.
`Nitrogen intake had a significant effect on
`plasma-bound half-cystine and taurine concentra(cid:173)
`tions and on urine methionine, cystathionine, and
`free cyst(e)ine levels. Nitrogen intake also had a
`significant effect on a number of other plasma
`amino acid levels (Table 4).
`The urine methionine concentrations in the in(cid:173)
`fants receiving cysteine supplementation reported
`here are low. We are concerned that this is an ar(cid:173)
`tifact produced by a lack of peak separation by the
`amino acid analyzer. Half-cystine is eluted from the
`analyzer column just prior to the elution of methi(cid:173)
`onine. In the infants receiving supplementation the
`large half-cystine peaks measured in the urine may
`have incorporated the methionine peaks.
`We calculated the total sulfur intake, the total
`sulfur retained, and the percentage of the total
`sulfur intake retained (Table 5). Aminosyn contains
`sulfur in the form of methionine (21.5% sulfur) and
`the antioxidant perservative potassium metabisul(cid:173)
`fite which provides approximately 18 mg/dl of sulfur
`per deciliter of Aminosyn. In the infants receiving
`supplementation cysteine was· the only other major
`source of sulfur (26.5% sulfur). Although sulfur(cid:173)
`containing medications were given to all the infants,
`
`J Pediatr Gastroenterol Nutr, Vol. 3, No. 2, 1984
`
`TABLE 4. Effect of nitrogen intake on plasma
`amino acid levels
`
`Nitrogen intake
`240 mg/kg/daya
`(µmol/dl)
`n = 10
`
`Nitrogen intake
`400 mg/kg/dayh
`(µmol/dl)
`n = 10
`
`16.5 ± 7.8
`10.9 ± 8.1
`3.2 ± 2.0
`5.5 ± 3.6
`5.7 ± 1.6
`12.4 ± 7.7
`
`11.9 ± 8.0
`29.4 ± 12.3
`10.5 ± 3.0
`8.6 ± 4.0
`3.6 ± 2.9
`5.0 ± 2.5
`25.1 ± 12.3
`0.8 ± 0.6
`2.9 ± 1.9
`4.9 ± 1.3
`
`32.0 ± 13.9d
`17.2 ± 5.3d
`5.1 ± 1.8'
`8.8 ± 2.8'
`5.3 ± 2.0
`17.1 ± 9.9
`
`20.4 ± 7.4'
`65.3 ± 22.0d
`24.9 ± 10.3d
`17.6 ± 5.6d
`8.1 ± 4.9d
`9.1 ± 5.0
`38.6 ± 16.7
`0.6 ± 0.6
`2.3 ± 2.4
`6.6 ± 1.9
`
`Essential
`Threoninec
`Valine<
`Isoleucine<
`Leucine<
`Phenylalanine<
`Lysine<
`Nonessential
`Alanine<
`Glycine<
`Serine<
`Proline<
`Arginine<
`Ornithine
`Glutamate
`Aspartate
`Tyrosine<
`Histidinec
`
`a Mean ± SD of Group 1 and Group 2 concentrations. There
`were no differences between these two groups.
`b Mean ± SD of Group 3 and Group 4 concentrations. There
`were no differences between these two groups.
`c Present in amino acid solution.
`d p < 0.01, e p < 0.05. The amino acid concentration at an
`intake of 400 mg/kg/day nitrogen was significantly different from
`the amino acid concentration at 240 mg/kg/day nitrogen.
`
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`CYSTEINE-SVPPLEMENTED TOTAL PARENTERAL NUTRITION
`
`243
`
`TABLES. Comparison of total sulfur intake and
`total sulfur retaineda
`
`Group no.
`
`1
`2 ( + cysteine)
`3
`4 ( + cysteine)
`
`Total sulfur
`intake
`(mg/kg/day)h
`
`Total sulfur
`retained
`(mg/kg/day)'
`
`Retention
`(%)
`
`18.l ± 3.2
`38.2 ± 3.4d
`31.6 ± 4.3
`50.1 ± 3.6
`
`12.0 ± 5.2
`29.5 ± 2.lf
`12.4 ± 6.7
`27.2 ± 5.5
`
`65 ± 20
`77 ± 6'
`38 ± 20
`54 ± 9
`
`a Values are means ± SD.
`b Total sulfur intake was calculated as the sum of the sulfur
`contained in the amino acid solution (Aminosyn) in the form of
`methionine and potassium metabisulfite. The quantity of sulfur
`in cysteine has been added for those groups receiving cysteine.
`c Total sulfur retained was calculated as the total sulfur intake
`minus the total sulfur excreted (total sulfur excreted = urine
`sulfur in the form of methionine + cysteine + cystathionine +
`taurine + sulfate).
`d p < 0.05, • p < 0.005 ,f p < 0.0005. Group 2 was significantly
`different from Group 3.
`
`the quantity of sulfur intake from this source has
`been estimated to be low (14). Our calculations
`show little absolute increase in sulfur retention with
`an increase in sulfur intake when Group 1 is com(cid:173)
`pared to Group 3 (12.0 ± 5.2 vs. 12.4 ± 6.7 mg/kg/
`day) or when Group 2 is compared to Group 4 (29.5
`± 2.1 vs. 27.2 ± 5.5 mg/kg/day). The addition of
`cysteine, however, appears to enhance sulfur reten(cid:173)
`tion. Although the total sulfur intakes of Group 2
`(38.2 ± 3.4 mg/kg/day, cysteine supplementation)
`and Group 3 (31.6 ± 4.3 mg/kg/day, no supplemen(cid:173)
`tation) are not exactly comparable, the absolute
`quantity of sulfur retained by Group 2 is more than
`twofold greater than that retained by Group 3 (29.5
`± 2.1 vs. 12.4 ± 6.7 mg/kg/day, p < 0.0005).
`
`DISCUSSION
`
`Our data show no significant enhancement of ni(cid:173)
`trogen retention when TPN solutions are supple(cid:173)
`mented with cysteine at nitrogen intakes of approx(cid:173)
`imately 240 and 400 mg/kg/day. These results
`concur with the findings of Zlotkin and Anderson
`(8). Our data differ from their data in that we ob(cid:173)
`served a more obvious effect of cysteine supple(cid:173)
`mentation on plasma cyst(e)ine concentrations. We
`attribute this observation to the method we used for
`measuring cyst(e)ine that measures both the sulfby(cid:173)
`dryl and disulfide forms of this compound. We dem(cid:173)
`onstrated previously that a significant quantity of
`cysteine infused parenterally remained in the
`sulfbydryl form in the plasma and urine and that
`
`automated amino acid analysis could not measure
`accurately free cyst(e)ine in the plasma or urine
`(15) .
`Nitrogen intake had a significant effect on
`plasma-bound half-cystine and taurine and urine
`methionine, cystathionine, and free cyst(e)ine con(cid:173)
`centrations. The effect on these sulfur-containing
`amino acid levels observed after an increase in ni(cid:173)
`trogen intake is likely to be the effect of methionine
`intake which increases concomitantly with nitrogen
`intake. The decrease in the concentration of
`plasma-bound half~cystine with an increase in ni(cid:173)
`trogen intake is an observation for which we have
`no ready explanation. The fact that plasma taurine
`and urine cyst(e)ine concentrations increased at the
`higher nitrogen intake suggests that the metabolic
`pathway from methionine to taurine is active. This
`observation supports the reports of Gaull et al. (4)
`and Zlotkin and Anderson (5) that the activity of
`hepatic cystathionase, the rate-limiting enzyme in
`the synthesis of cysteine from cystathionine, ma(cid:173)
`tures rapidly with postnatal age.
`Sulfate excretion in the urine was not affected by
`cysteine intake but was significantly affected by an
`increase in nitrogen intake (p < 0.0001).
`We observed a greater retention of sulfur in in(cid:173)
`fants receiving cysteine supplementation, as did
`Zlotkin and Anderson (14). As the requirements for
`sulfur-containing amino acids or inorganic sulfur
`are met , however, the percentage of additional
`sulfur retained decreases. The surplus sulfur is ex(cid:173)
`creted, primarily in the form of sulfate. Previous
`investigators have correlated sulfur intake with sul(cid:173)
`fate excretion (16, 17).
`Cysteine supplementation had no significant ef(cid:173)
`fect on the other plasma amino acid levels that we
`measured. The increase in nitrogen intake from 240
`mg/kg/day to 400 mg/kg/day, however, resulted in
`concentration increases in a number of plasma
`amino acids. Based on weight gain there appears to
`be no particular advantage in infusing more nitrogen
`when the caloric intake is low. Based on nitrogen
`retention data the infusion of more nitrogen results
`in enhanced nitrogen retention even at low caloric
`intakes. The advantages of the higher nitrogen re(cid:173)
`tention and the fate of the retained nitrogen are un(cid:173)
`certain.
`Whether or not cysteine can be considered an
`essential amino acid for the newborn, in particular
`the preterm infant, is from our perspective still un(cid:173)
`certain. Data from our studies and from Zlotkin's
`observations indicate that cysteine does not en-
`
`. J Pediatr Gastroenterol Nutr, Vol. 3, No . 2, 1984
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`244
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`M. H. MALLOY ETAL.
`
`hance nitrogen retention. Based on sulfur retention
`data, however, cysteine appears to be preferentially
`retained. We suggest that cysteine is probably re(cid:173)
`tained in the form of hepatic glutathione. The liver
`of an adult human contains large quantities of glu(cid:173)
`tathione ('y-glutamyl-cysteinyl-glycine) which has
`been proposed as a reservoir for cysteine (18).
`The lack of effect of cysteine supplementation on
`nitrogen balance may be closely related to the con(cid:173)
`centration of cysteine held in reserve in the liver as
`glutathione. Over a short period of time it seems
`likely that, in the absence of an exogenous source
`of cysteine, glutathione may be an adequate source
`of cysteine for growth so that the nitrogen balance
`may not be affected. Whether or not the addition
`of cysteine to TPN solutions offers advantages in
`enhancing glutathione metabolism in the human in(cid:173)
`fant remains unknown.
`
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`J Pediatr Gastroenterol Nutr, Vol. 3, No. 2, 1984
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`6 of 6
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