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Methionine and Cysteine Kinetics at Different Intakes of Methionine and Cystine in Elderly Men and Women1–3

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Methionine and Cysteine Kinetics at Different Intakes of Methionine and Cystine in Elderly Men and Women1–3 Methionine and cysteine kinetics at different intakes of methionine and cystine in elderly men and women1–3 Naomi K Fukagawa, Yong-Ming Yu, and Vernon R Young See corresponding editorial on page 224. Downloaded from https://academic.oup.com/ajcn/article/68/2/380/4648746 by guest on 27 September 2021 ABSTRACT Earlier nitrogen balance studies led to the con- requirement for methionine. On the other hand, recent kinetic clusion that requirements for methionine in older individuals are studies by Fereday et al (6) imply that the protein requirements much higher than those in younger adults. Hence, we examined of healthy elderly, at least as assessed from tracer leucine bal- the kinetics of whole-body methionine, cysteine, and leucine ance studies, may not be any higher than those of younger adults. metabolism postabsorptively using a continuous intravenous Indeed, there is a great deal of uncertainty about the protein and 2 13 2 infusion of L-[C H3,1- C]methionine, L-[ H3]leucine, and [3,3- amino acid requirements of elderly subjects and the effects of 2 H2]cysteine in 12 elderly men (n = 5) and women (n = 7) given aging (7–9); therefore, further relevant studies in this age group as a 3-h infusion after a 12-h fast (study 1) and in 8 elderly men are highly desirable. In a review published previously (8), we (n = 4) and women (n = 4) as an 8-h infusion according to a 3-h concluded that amino acid requirements are similar in healthy fasted, 5-h fed protocol (study 2) for 6 d. Before tracer infusion, younger and older subjects. each of 3 L-amino acid diets supplying the following nominal, This article presents the results of 2 studies of plasma methion- but known, amounts (mg·kg21 ·d21) of methionine and cystine, ine and cysteine kinetics. Because no studies have been reported respectively, were used in study 2: diet 1: 13 and 0; diet 3: 6.5 on methionine kinetics in the elderly, the first study was carried and 5.2; and diet 5: 6.5 and 21. Studies 1 and 2 gave values for out to obtain initial data on the dynamic status of whole-body plasma methionine flux that agreed with the leucine flux data, methionine and cysteine metabolism postabsorptively in elderly which, in turn, also appeared to be comparable with findings in men and women and, in particular, its relation to plasma leucine healthy younger adults. In study 2, methionine oxidation rates kinetics. There are more extensive data on leucine kinetics in the were the same across all diets in the fasted state and the same elderly (10, 11) and so we considered it important to begin our with diets 1 and 3 in the fed state but lower with diet 5, suggest- investigation of sulfur amino acid metabolism in this age group. ing a modest sparing effect of dietary cystine on methionine oxi- In addition, we thought that this study would provide an addi- dation. Estimated daily methionine balance was at equilibrium tional means of judging the suitability of the correction factor for diet 1 and negative (significantly different from zero, that we used previously (1, 12, 13) and in this study (study 2) to P<0.05) with diets 3 and 5. The results were evaluated against estimate methionine oxidation. We examined the dynamic status our previous findings in younger adults. Am J Clin Nutr of methionine metabolism at different intakes of methionine and 1998;68:380–8. cystine in healthy elderly subjects. KEY WORDS Balance study, amino acid requirements, kinetics, oxidation, protein turnover, methionine, leucine, cys- SUBJECTS AND METHODS tine, elderly Subjects Two separate studies were conducted. In study 1 (postabsorp- INTRODUCTION tive), 5 elderly men and 7 elderly women in generally good We studied plasma methionine and cysteine kinetics previous- ly in healthy young adult men and women and found little evi- 1 From the University of Vermont, the Department of Medicine and the dence for a sparing effect of dietary cystine on the requirement Clinical Research Center, Burlington; the Laboratory of Human Nutrition, for dietary methionine, other than at an extremely low methion- School of Science and the Clinical Research Center, Massachusetts Institute ine intake (1–3). However, nitrogen balance studies by Tuttle et of Technology, Cambridge; and the Shriners Burns Institute, Boston. 2 al (4) led them to suggest that methionine and lysine require- Supported by NIH grants AG 00599, DK15856, DK42101, RR00088, and RR00109, and by grants from the Shriners Hospital for Crippled Chil- ments in older individuals are much higher than those estab- dren. Ajinomoto Inc, Teaneck, NJ, donated the amino acids. lished, with similar procedures, in young adults. Hence, in com- 3 Address reprint requests to NK Fukagawa, University of Vermont, Col- parison with the young, it is possible that older individuals lege of Medicine, Given Building, Room C-207, Burlington, VT 05405-0068. would also have higher requirements for the sulfur amino acids E-mail: [email protected]. as judged from methionine tracer balance studies (5) and might Received September 19, 1997. be more sensitive to a sparing effect of dietary cystine on the Accepted for publication February 23, 1998. 380 Am J Clin Nutr 1998;68:380–8. Printed in USA. © 1998 American Society for Clinical Nutrition METHIONINE KINETICS 381 TABLE 1 for blood sampling. The isotope tracers were given as a primed, Composition of the L-amino acid mixtures used (expressed as nominal continuous intravenous infusion, as described previously (1). intakes) to study methionine and cysteine kinetics in elderly subjects The bicarbonate pool was primed with 0.8 mmol [13C]sodium Diet bicarbonate/kg (99 atom%; Cambridge Isotope Laboratories, Amino acid 1 3 5 Inc) before the continuous isotope infusion began. The known mean infusion rates for methionine, cysteine, and leucine were mg·kg21 ·d21 1.7, 0.7, and 5.1 mmol·kg21 ·h21, respectively. Blood and L-Methionine 13 6.5 6.5 expired breath samples were obtained at timed intervals L-Cystine 0 5.2 20.9 between 120 and 180 min of the tracer infusion for determina- L-Tryptophan 6.0 6.0 6.0 tion of plasma methionine, cysteine, leucine, and a-ketoiso- L-Threonine 15.0 15.0 15.0 caproic acid (KIC) isotopic enrichments and for 13C enrichment L-Isoleucine 23.0 23.0 23.0 in expired carbon dioxide. Total carbon dioxide production and L-Leucine 40.0 40.0 40.0 L-Lysine·HCl 30.0 30.0 30.0 oxygen consumption were measured with a ventilated-hood sys- L-Phenylalanine 25.9 25.9 25.9 tem (Delta-Trac Metabolic Monitor; Sensor Medics Corp, Yorba Downloaded from https://academic.oup.com/ajcn/article/68/2/380/4648746 by guest on 27 September 2021 L-Tyrosine 13.0 13.0 13.0 Linda, CA) as described previously (1). L-Valine 20.0 20.0 20.0 Study 2 L-Histidine HCl·H2O 12.0 12.0 12.0 L-Arginine·HCl 73.5 73.5 73.5 The diets used in this study were semisynthetic and the pro- L-Alanine 124.4 124.4 122.7 tein component was supplied as a mixture of L-amino acids. The L-Aspartic acid 185.8 185.8 183.4 major proportion of energy intake, other than that supplied by L-Glutamic acid 205.4 205.4 202.6 the amino acid mixture and beet sucrose, was provided as pro- Glycine 104.8 104.8 103.4 tein-free, wheat-starch cookies. Vitamins were supplied as a L-Proline 160.6 160.6 158.5 L-Serine 146.7 146.7 144.7 daily supplement to meet recommended dietary allowances (14) Total amino acids 1198.4 1197.1 1200.1 and safe intakes. Macromineral supplements provided sodium, Total nitrogen intake 160 160 160 potassium, calcium, and phosphate at amounts within the range (mg N·kg21 ·d21) of recommended dietary allowances (14). A trace mineral mix- ture, provided as a capsule, supplied magnesium and those trace minerals not present in the vitamin and mineral supplements. health, as assessed by a medical history, physical examination, Choline was added as a supplement to provide an intake of 500 and routine blood and urine tests, participated. Their mean mg/d. The basic diet was described previously (1). (±SD) age was 74 ± 2 y (range: 66–92 y) and they weighed Three diets based on different formulations of the L-amino 68 ± 11 kg (range: 49–85 kg). None were taking medications and acid mixture were used (Table 1). They are designated as diets all consumed regular “house” diets supplying ≥ 1 g 1, 3, and 5 because they were the same as those used in our pre- protein·kg21 ·d21 and energy estimated to be adequate for vious studies in young adults (1). Each diet was offered to the weight maintenance. Subjects were studied as inpatients in the subjects in random order and each began after 7–14 d of a break Clinical Research Center (CRC) of the Massachusetts Institute between the diets, during which subjects ate usual foods. The of Technology (MIT). Written informed consent was obtained in control, amino acid mixture supplied 13.2 mg methio- accordance with the protocol approved by the MIT Committee nine·kg21 ·d21 (87 mmol·kg21 ·d21) and no cystine (diet 1) dur- on the Use of Humans as Experimental Subjects and the CRC ing the 6 d before the tracer studies. This amino acid mixture was Scientific Advisory Committee. similar to that used in a previous tracer-metabolic study (1) but In study 2 (which involved methionine and cystine intakes), 8 it supplied a somewhat lower daily intake of methionine than we normal-weight (64 ± 3 kg), elderly men (n = 4) and women had used in our initial series of studies of methionine kinetics (3, (n = 4) aged 79 ± 7 y (range: 71–92 y) participated.
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