Plasma and urinary amino acid levels were measured in four normal adult subject administered equimolar quantities (0.0605 mmol/kg body wt) of L-methionine, D-methionine and L-methionine-dl-sulfoxide in a randomized crossover design. Plasma total methionine concentrations increased significantly (P less than 0.05) over base line (3.7 +/- 1.2 mumol/dl; mean +/- SD) after loading with each compound. Mean peak plasma methionine levels were 9.8 +/- 1.1, 14.4 +/- 2.3 and 5.2 +/- 1.0 mumol/dl after loading with L-methionine, D-methionine and L-methionine sulfoxide, respectively. D-Methionine accounted for the increased plasma levels seen after D-methionine loading. None of the three compounds affected plasma cystine, cysteine or taurine concentrations. Plasma methionine sulfoxide concentrations were not affected by loading with D- or L-methionine but increased significantly after ingestion of L-methionine sulfoxide. Urinary methionine excretion was 20 times higher after ingestion of D-methionine than after ingestion of L-methionine or L-methionine sulfoxide, with the increase due to D-methionine excretion. Urinary excretion of methionine sulfoxide and its N-acetyl derivatives was not significantly higher after loading with methionine sulfoxide. The data indicate that adult humans do not utilize D-methionine efficiently as a methionine source but probably do utilize L-methionine-dl-sulfoxide.

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ExtractRates of urinary excretion of total hydroxyproline by 38 normal fullsize male infants were determined on 176 occasions. Each urine collection period was 72 hours. When the period of urine collection was begun between the fourth and eighth day of life, mean rate of excretion was 30.6 mg/day (standard deviation 6.9 mglday). Maximal rates of urinary excretion were observed between 21 and 60 days of age (mean: 48.1 mglday; standard deviation 9.7 mg/day). Between 121 and 582 days of age, mean rate of excretion had decreased slightly to 43 mglday.Eleven infants were each studied on at least five occasions between 20 and 120 days of age. Mean rate of urinary excretion of hydroxyproline by each infant was shown to be significantly correlated with rate of gain in length but not with rate of change in weight or surface area. SpeculationDuring normal infancy it seems probable that a major proportion of the hydroxyproline excreted in the urine is derived from collagen of bone. Rate of excretion probably parallels rate of bone growth. Thus, any disorder that depresses the normal rate of linear growth is likely to result in sharp diminution of urinary excretion of hydroxyproline. Such a biochemical index of growth may be clinically useful. Introductionuseful and may contribute to our understanding of growth. The nonessential amino acid, hydroxyproline, accounts Newly formed collagen is soluble in neutral salt solufor about 13 % by weight of collagen and about 1.5 % tions and is metabolically quite active, while mature colby weight of elastin [18]. Because hydroxyproline is not lagen is insoluble and metabolically relatively inert. Alfound in other body tissues and because the amount of though newly formed collagen accounts for only a small collagen in the body is so much greater than the amount percentage of total body collagen, its contribution to of elastin, urinary excretion of endogenous hydroxyurinary excretion of endogenous hydroxyproline is relaproline is derived almost entirely from collagen. A numtively great. In view of this considerable contribution ber of studies have suggested that rate of urinary excreof newly formed collagen to urinary excretion of hydrotion of hydroxyproline reflects rate of collagen metaxyproline, it is not surprising that rates of excretion, exbolism [2,6,7,8,9,11,13,15,17,18, 191. Studies of pressed as milligrams/day, have generally been reporthydroxyproline excretion may therefore be clinically ed to be somewhat greater in children than in adults.

Rats and chickens, unlike man, utilize D-methionine efficiently. We have studied urinary excretion of methionine isomers in young miniature pigs, adult rabbits, and adult dogs given D-methionine in an attempt to find an animal model that, like man, utilizes the D-isomer poorly. Six-week-old miniature pigs ingesting a protein-free diet were infused with 8.5% amino acid solutions differing only in methionine isomer content (L- vs DL-) to supply amino acid requirements. Each solution was infused for a 2- or 3-day period in a cross-over design. Plasma methionine levels were significantly higher (p = 0.01) during infusion of the solution providing DL-methionine, with 25% of total plasma methionine present as the D-configuration. However, urinary methionine excretion was similar with both solutions, with D-methionine utilization calculated as greater than 99%. Adult rabbits ingesting DL-methionine (0.14 g/100 g food) showed good utilization of D-methionine, excreting less than 1.3% D-isomer in the urine. Mixed breed dogs given 1.25 g D-methionine in their drinking water excreted less than 0.4% of ingested D-methionine in the urine. These data indicate that the pig, rabbit, and dog utilize D-methionine efficiently, behaving like the rat and chicken rather than man.

N-Acyl-methionine derivatives have been proposed as replacements for methionine in supplementing food products low in this amino acid. We studied the effects of N-acetyl-L-methionine, N-acetyl-D-methionine and L-methionine loads (2 mmol/kg body weight) on portal and vena caval plasma amino acid concentrations in young pigs (n = 4). L-Methionine loading significantly increased mean (+/- SD) portal and vena caval plasma methionine concentrations from baseline values of 6.44 +/- 1.03 and 6.63 +/- 0.99 mumol/100 ml, respectively, to mean peak values of 340 +/- 75.0 and 265 +/- 49.8 mumol/100 ml, respectively. N-Acetyl-L-methionine loading increased mean peak portal and vena caval plasma methionine concentrations to 291 +/- 85 and 220 +/- 51.6 mumol/100 ml, respectively. N-Acetyl-L-methionine could not be detected in either portal or vena caval plasma. In contrast, N-acetyl-D-methionine loading produced only a small rise in mean peak portal and vena caval plasma methionine concentrations (13.0 +/- 4.31 and 8.62 +/- 1.71 mumol/100 ml, respectively). Concentrations of N-acetyl-D-methionine increased from baseline values of 0 mumol/100 ml to mean peak values of 251 +/- 32.0 and 234 +/- 72.3 mumol/100 ml, respectively, in portal and vena caval plasma. These data explain the poor utilization of N-acetyl-D-methionine as a methionine source.