Johannes Mårtensson

ASSOCIATION OF HIGH CYANIDE AND LOW SULPHUR INTAKE IN CASSAVA-INDUCED SPASTIC PARAPARESIS

Urinary excretion of sulphur compounds was studied in children from a population in Mozambique that had been affected, during a drought, by an epidemic of spastic paraparesis attributed to cyanide exposure from cassava. The children had increased thiocyanate and decreased inorganic sulphate excretion, indicating high cyanide and low sulphur-containing amino-acid intake. Children from a neighbouring cassava-eating area, where no cases of spastic paraparesis had occurred, had lower thiocyanate excretion but higher inorganic sulphate excretion. These results support the hypothesis that the epidemic was due to the combined effects of high dietary cyanide exposure and sulphur deficiency.

The effect of fasting on leukocyte and plasma glutathione and sulfur amino acid concentrations

Leukocyte and plasma concentrations of free glutathione, cysteine, methionine, and taurine, and total glutathione and cysteine concentrations were determined in healthy human subjects before and during a seven-day period of total energy deprivation. In leukocytes a progressive decline in total glutathione concentration was found during seven days of starvation due to a decrease in free glutathione content. An increased mixed protein-bound glutathione concentration was calculated, whereas the total cysteine level was unaltered. Fasting resulted in a decreased plasma concentration of free glutathione, whereas the total glutathione level remained unchanged. Free leukocyte concentrations of taurine and methionine were reduced, whereas plasma sulfur amino acid levels were essentially unaffected. These results probably reflect a limited availability of sulfur amino acids during fasting, when glutathione is used as cysteine reservoir for synthesis of other vital sulfur containing compounds. The potential use of leukocyte glutathione, methionine, and taurine concentrations as intracellular indicators of sulfur amino acid deficiency are stressed.

Splanchnic and peripheral release of 3-methylhistidine in relation to its urinary excretion in human infection☆

The present investigation was undertaken in order to determine the release of 3-methylhistidine (3MH) from the splanchnic region and from the leg, and the contributions these make to the increase in urinary 3MH excretion in infection. Thirteen febrile patients with infection were investigated. After an overnight fast, hepatic vein, femoral vein, and radial artery catheterizations were performed. Splanchnic and leg blood flows were determined by dye dilution technique. Plasma 3MH was analyzed by a modified HPLC method. The release of 3MH from the leg was 0.064 +/- 0.007 mumol/min (+/- SE) and from the splanchnic region 0.012 +/- 0.013 mumol/min. These releases of 3MH constitute 27% +/- 2% and 8% +/- 6% of the individual urinary excretions, respectively. With increasing degree of catabolism, measured as individual 3MH increase above baseline excretion or as the 3MH to creatinine ratio (3MH:Cr), the relative contribution to urinary excretion from the leg was increased (individual increase, P = 0.08; 3MH:Cr, P less than 0.01). Since this contribution was not decreased in the more catabolic patients, as would have been expected if the increase in urinary 3MH originated elsewhere, it is concluded that skeletal muscle is the source, and these results thus validate the use of urinary 3MH excretion as a marker of myofibrillar protein catabolism in infected patients.

Urinary excretion of carnitine and its derivatives in newborns

Abstract The inclusion of an SH-trapping compound in the radioenzymatic carnitine method based on the conversion of radioactive acetyl-CoA to acetylcarnitine in the presence of carnitine acetyltransferase results in linear standard curves. N-Ethylmaleimide was preferred since the amount of free carnitine was less overestimated when acetylcarnitine was present compared to tetrathionate. Urinary excretion of carnitine and its derivatives was determined in 13 healthy fullterm boys. On Days 3 and 6 after delivery, total carnitine excretion was similar, 7.5 μmol/24 hr ± 0.90 (SE) and 7.0 μmol 24 hr ± 1.16 (SE) despite the ingestion of more breask milk on Day 6. Regarding the distribution of free, acyl, and total carnitine, the variation between individuals was large. Weak but significant differences were noted pointing at a higher degree of carnitine acylation on Day 3. It was shown by a comparison of these variables between the newborns and healthy boys, 8–15 years, that the newborns had a markedly increased acylation degree of carnitine. The changes may be consistent with the fact that lipids are the major energy source in the neonatal period.

3-Mercaptolactate cysteine disulfiduria: Biochemical studies on affected and unaffected members of a family

Abstract Mercaptolactate cysteine disulfiduria (MCDU) was detected in an adult, mentally normal woman. Studies of family members revealed that her father also excreted increased amounts of mercaptolactate, although less than that of the propositus. An increased excretion of mercaptoacetate was also found in both subjects. Erythrocytes from the propositus were devoid of activity of the enzyme mercaptopyruvate sulfrutransferase (MST) and those from her father showed an abnormally low activity. Slightly reduced red cell MST activity together with a slightly increased urinary excretion of mercaptolactate was found in some of the family members and allowed the tentative classification of MCDU as an autosomal recessive hereditary disorder. An increased urinary excretion of mercaptopyruvate was demonstrated in the propositus but not in her father. The excretion of thiosulfate and thiocyanate from both subjects was within the normal range, indicating that significant amounts of these compounds are not formed in human beings through the action of MST.

Sulfur amino acid metabolism in juvenile-onset nonketotic and ketotic diabetic patients.

Sulfur amino acid metabolism was studied in non-fasting nonketotic and ketotic juvenile-onset diabetic children and the results were compared to age-matched healthy children on an ordinary diet. An increased excretion of total sulfur and inorganic sulfate was found in diabetic children, probably a result of a decreased protein-serum synthesis and/or increased endogenous protein catabolism, although as a result of hyperglycemia a decreased tubular reabsorption may also have contributed. All diabetics showed a normal excretion of methionine. For cyst(e)ine and taurine an increased excretion was seen in ketotic diabetics, probably also a consequence of an increased endogenous protein degradation. As a sign of the latter, an increased output of 3-methylhistidine was also observed, a confirmation of earlier reports. The increased output of mercaptolactate and mercaptoacetate found in ketotic patients, was probably also a result of enhanced endogenous protein degradation. An increased urinary excretion of N-acetylcysteine was seen in diabetic children, which may reflect an enhanced availability to acetyl coenzyme A.

Human β-mercaptopyruvate sulfurtransferase: Distribution in cellular compartments of blood and activity in erythrocytes from patients with hematological disorders

The distribution of mercaptopyruvate sulfurtransferase (EC 2.8.1.2) in human blood cell compartments has been studied. Almost all of the enzyme activity in whole blood was confined to erythrocytes, but the activity per litre cell volume was higher in platelets than in erythrocytes. Leukocytes contained very low concentrations of the sulfurtransferase and plasma was devoid of activity. The enzyme activity of blood hemolysates from normal subjects and patients with various erythrocyte disorders was also determined. Significantly higher sulfur transferase activity was found in male subjects in comparison with females. The enzyme activity per litre erythrocytes was increased in blood from patients with iron deficiency anemia, whereas less clear-cut differences with respect to normals were found in other diseases studied.

The excretion of sulfur compounds in the urine of newborn infants

The excretion of sulfur-containing compounds was determined on the third and sixth day of life in male infants and the results were compared with those previously obtained on fed and fasting men. The output of total sulfur and inorganic sulfate was very low on the third day of life but had increased by the sixth day to levels found in the fasting men, whereas the excretion of mercaptolactate in the newborns decreased from the third to the sixth day of life. These results may be explained by the initial fasting state of neonates followed by an anabolic phase. Neonates excreted acid-labile ester sulfate and mercaptoacetate at levels similar to those found in adults, but the neonatal urine also contained sulfate esters (probably steroid sulfates) that required more drastic acid conditions for hydrolysis. Raised concentrations of sulfur-containing amino acids (methionine, cystathionine, cyst(e)ine and taurine) were found in neonatal urine in confirmation of earlier reports. The excretion of thiosulfate could only be determined in newborns on the sixth day and was low in comparison with that of adults. High urinary thiocyanate concentrations were found in newborns fed by tobacco-smoking mothers, whereas the excretion of thiocyanate was low in other newborns. The possible medical hazards from the exposure of neonates to thiocyanate are emphasized.

Metabolic effects of a human milk adapted formula on sulfur amino acid degradation in full-term infants

The metabolic effects of formula feeding on sulfur amino acid degradation were studied in 6 full-term infants on the 6th day of life, and compared to corresponding data from breast-milk fed neonates. A normal excretion of total sulfur and inorganic sulfate was found, indicating an adequate intake of sulfur amino acids and a normal ability to oxidized these compounds to inorganic sulfate. A similar transaminative degradation of cysteine was observed in both groups. Formula-fed infants showed a normal output of methionine, whereas increased cystathionine and decreased taurine excretions were registered. The results were probably a combined effect of a limited intake of taurine, and a multiple immature enzymatic activity.

The decarboxylation of 3-mercaptopyruvate to 2-mercaptoacetate

Rat brain mitochondria were found to convert 3‐mercaptopyruvate to 2‐mercaptoacetate in the presence of NAD+ coenzyme A and thiamin pyrophosphate. The overall reaction probably consists of an oxidative decarboxylation of 3‐mercaptopyruvate with 2‐mercaptoacetyl CoA as a product which is then hydrolyzed to 2‐mercaptoacetate by acyl CoA hydrolase