THE RELATION OF SULFUR METABOLISM TO ACID-BASE BALANCE AND ELECTROLYTE EXCRETION: THE EFFECTS OF DL-METHIONINE IN NORMAL MAN Jacob Lemann Jr., Arnold S. Relman J Clin Invest. 1959;38(12):2215-2223. https://doi.org/10.1172/JCI104001. Research Article Find the latest version: https://jci.me/104001/pdf THE RELATION OF SULFUR METABOLISM TO ACID-BASE BALANCE AND ELECTROLYTE EXCRETION: THE EFFECTS -OF DL-METHIONINE IN NORMAL MAN *t By JACOB LEMANN, JR. AND ARNOLD S. RELMAN WITH THE TECHNICAL ASSISTANCE OF HELEN P. CONNORS (From the Department of Medicine, Boston University School of Medicine, and the Evans Memorial Department, Massachusetts Memorial Hospitals, Boston, Mass.) (Submitted for publication June 15, 1959; accepted August 31, 1959) It has been known for many years that most of information about the interrelationships of changes the inorganic sulfate in the urine is derived from in systemic acid-base balance, urinary excretion the oxidation of sulfur-containing organic com- of acid and electrolytes and the metabolism of pounds. In the classical calculation of the "acid- organic sulfur is currently available. The present base balance" of food each Mole of sulfur in the work was therefore designed to clarify this prob- ash is assigned an acid equivalence of two, thus lem by carrying out balance studies of the effects assuming its quantitative conversion to sulfuric of large loads of DL-methionine in normal men. acid or to some other strong acid or acids which yield a total of two equivalents of hydrogen ion METHODS AND MATERIALS per Mole of sulfur (1). Five balance studies were performed on three healthy Until recently, however, there have been virtu- young adult males who carried on their usual daily ally no studies of the relationship of sulfur metabo- activities during the period of observation. Each study lism to acid-base balance. In 1956 Hunt (2) re- was preceded by a two to four day period of adaptation ported that the feeding of methionine or sulfur- to the standard diet. The balance then began with a control period, followed by a period of DL-methionine containing foods to man increased the excretion of loading, and a recovery period, each lasting five to six acid in the urine. He suggested that it is chiefly days. the oxidation of dietary sulfur that determines the Liquid formula diets were utilized, which provided urinary excretion of acid. Interest in the rela- 35 to 40 calories per Kg. body weight and 70 to 90 Gm. tion of sulfur metabolism to the acidification of the protein per day. A soybean flour'1 was used as the urine has also been stimulated by the observation protein source, and had the following composition: that administration of methionine is an effective Protein 50 per cent for maintaining an acid urine in some Fat 1 to 2 per cent technique Carbohydrate 30 to 35 per cent patients with chronic urinary tract infection (3). Calcium 0.2 to 0.4 per cent Small reductions in plasma CO2 content have Phosphorus 0.5 to 0.7 per cent been observed in subjects given large doses of Potassium 57 mEq. per 100 Gm. methionine (4), thus further suggesting a con- Sodium < 1 mEq. per 100 Gm. nection between the metabolism of organic sulfur Chloride < 1 mEq. per 100 Gm. and acid production. Corn oil and glucose served as sources of fat and car- bohydrate, respectively. In three balance studies 200 mEq. Although on theoretical grounds the release of sodium chloride was provided daily in the diet, while in two hydrogen ions would-appear to be an obliga- two studies no sodium chloride was added. The sub- tory consequence of the biological oxidation of jects drank a constant amount of tap water and took one methionine-sulfur to sulfate in an aqueous medium, multiple vitamin capsule each day. Some subjects took small amounts of instant coffee either mixed with the there is at present no experimental demonstration diet or in the supplementary water, and in these cases of this relationship. No detailed or quantitative the coffee was included in the diet analyses. Since the flour contained 0.7 Gm. methio- * Supported by Grant H-2767, National Heart In- soybean only stitute, United States Public Health Service. 1 "Toasted Soy Protein" granular flour, kindly made t Presented in part at the Annual Meeting of The available by Soybean Division, General Mills, Inc., Min- American Physiological Society, April, 1959. neapolis, Minn. 2215 2216 JACOB LEMANN, JR. AND ARNOLD S. RELMAN > b UV e z U4 4 - 0 dr 0 C,) - oOaaON O* o*ka a o0 oo o o o M~~~~~~~C4oo" C4~bC4 4 a0e 0%0aeneneM MCee a n 0o000N000 aq C! la Sft~~O W)N In;; a~eeoooo(4 at-v) 0 0C4-0 C4 O4O4.r N0r ee e0 ao Pt.fiN Oe _ t'e VN) b b0 + £ o 0 b 0 0 _ NN-N- __NN_ -_S_ : d ~~~N00 w1 r O N' u~ U) ' UN - U) '0") uN N (4 W W)_o t )_Noc -4 0%C z ^ . ao r 0o*,rr o 0 00 rv ?s S e e O ON _O bN N b O z '0rz))00U)_-U-s tv) 00'0U?P )N . _Nt9_S_~~*4~0s____NNN 0 la 1~~~~~~~~~~~~~~~~~04 4o 04OU)'0>04 '0 U )0004c eP 0 * s40,-N 0W oo. 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DL-methionine per day was added to the basic diet dur- sodium or chloride. Potassium concentration de- ing the period of methionine loading. creased by 0.3 and 0.7 mEq. per L. in the two Urine was collected under mineral oil using thymol balances without added salt. and phenyl mercuric nitrate as preservatives. Excretion of inorganic sulfate increased rapidly Diets were analyzed for total nitrogen, sodium, potas- from control levels of 33 to 49 mEq. per day up to sium, chloride and phosphorus. The methods for these determinations, as well as those employed for the analy- 150 to 179 mEq. per day by the second or third ses of blood, urine and stool have been previously reported day of methionine administration. The maximum (5) with the following exceptions: urinary ammonia daily increments above the average control rates was determined by Conway's micro-diffusion method ranged from 110 to 130 mEq. per day. Excre- (6), ethereal sulfates in urine were determined gravi- tion of ethereal sulfate was measured in two bal- metrically as barium sulfate (7) and chloride in se- rum, urine, stools, and diet was determined by a po- ances and did not change (Table I). tentiometric titration (8). Urine pCO2 and bicarbonate Associated with the sulfate diuresis was a were calculated from the total CO2 content and pH of prompt fall in the pH of the 24 hour urine collec- the urine. Net urinary excretion of acid (referred to as tions to the range of 4.7 to 5.2 (starting from con- "net acid") was calculated as the sum of ammonia plus trol values of 5.8 to 7.0). The pH of individual titratable acid minus bicarbonate. freshly voided specimens varied from 4.5 to 5.5 throughout the day. There was also an immedi- RESULTS ate and progressive rise in ammonium excretion Analytical data from a representative balance on starting from control rates of 19 to 37 mEq. per one subject (J. L.) are presented in Table I, and day and rising gradually to levels of 92 to 115 some of the pertinent results from the other bal- mEq. per day by the fourth or fifth day of load- ances are shown in Figures 1 through 4. ing. Titratable acid increased by an average of 15 to 22 mEq. per day and remained fairly con- I. Effects of methionine loading stant throughout the period of loading. The ex- In each of the balance studies the administration cretion of "net acid" rose gradually and then of DL-methionine produced an immediate though leveled off after two or three days. As shown modest drop in serum CO2 content (Figure 1), in Figures 2 through 4, the increments in "net 2218 JACOB LEMANN, JR. AND ARNOLD S. RELMAN 1.0 _ Serum COz URINE 330 pH ImM./L. 6.0 F- - 5.0 24 120 soo 60 - NemN Aci 40 V IG 26SBETP.LWSDIMITK 20 Canba Ay.