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Summary: The CARMA1/CARD11-BCL10-MALT1 (CBM) complex bridges T and B cell antigen receptor (TCR/BCR) ligation to MALT1 protease activation and canonical nuclear factor κB (NF-κB) signaling. Using unbiased mass spectrometry, we discover multiple serine phosphorylation sites in the MALT1 C terminus after T cell activation. Phospho-specific antibodies reveal that CBM-associated MALT1 is transiently hyper-phosphorylated upon TCR/CD28 co-stimulation. We identify a dual role for CK1α as a kinase that is essential for CBM signalosome assembly as well as MALT1 phosphorylation. Although MALT1 phosphorylation is largely dispensable for protease activity, it fosters canonical NF-κB signaling in Jurkat and murine CD4 T cells. Moreover, constitutive MALT1 phosphorylation promotes survival of activated B cell-type diffuse large B cell lymphoma (ABC-DLBCL) cells addicted to chronic BCR signaling. Thus, MALT1 phosphorylation triggers optimal NF-κB activation in lymphocytes and survival of lymphoma cells. : Gehring et al. identify MALT1 phosphorylation as a process that bridges antigen receptor ligation to downstream signaling pathways in T cells, promotes T lymphocyte activation, and drives survival of B cell lymphoma tumor cells. Keywords: immune response, adaptive immunity, antigen receptor signaling, T cell activation, B cell lymphomas, CBM complex, phosphorylation, NF-kappa B, MALT1, casein kinase 1 alpha

Conventional ubiquitination regulates key cellular processes by catalysing the ATP-dependent formation of an isopeptide bond between ubiquitin (Ub) and primary amines in substrate proteins 1 . Recently, the SidE family of bacterial effector proteins (SdeA, SdeB, SdeC and SidE) from pathogenic Legionella pneumophila were shown to use NAD+ to mediate phosphoribosyl-linked ubiquitination of serine residues in host proteins2, 3. However, the molecular architecture of the catalytic platform that enables this complex multistep process remains unknown. Here we describe the structure of the catalytic core of SdeA, comprising mono-ADP-ribosyltransferase (mART) and phosphodiesterase (PDE) domains, and shed light on the activity of two distinct catalytic sites for serine ubiquitination. The mART catalytic site is composed of an α-helical lobe (AHL) that, together with the mART core, creates a chamber for NAD+ binding and ADP-ribosylation of ubiquitin. The catalytic site in the PDE domain cleaves ADP-ribosylated ubiquitin to phosphoribosyl ubiquitin (PR-Ub) and mediates a two-step PR-Ub transfer reaction: first to a catalytic histidine 277 (forming a transient SdeA H277–PR-Ub intermediate) and subsequently to a serine residue in host proteins. Structural analysis revealed a substrate binding cleft in the PDE domain, juxtaposed with the catalytic site, that is essential for positioning serines for ubiquitination. Using degenerate substrate peptides and newly identified ubiquitination sites in RTN4B, we show that disordered polypeptides with hydrophobic residues surrounding the target serine residues are preferred substrates for SdeA ubiquitination. Infection studies with L. pneumophila expressing substrate-binding mutants of SdeA revealed that substrate ubiquitination, rather than modification of the cellular ubiquitin pool, determines the pathophysiological effect of SdeA during acute bacterial infection. Structural and functional investigations demonstrate how bacterial enzymes ubiquitinate host proteins.

Organometallische Verbindungen sind in der Lage durch Ausweitung der Koordinationszahl im Vergleich zu rein organischen Verbindungen globuläre dreidimensionale Strukturen auszubilden. MEGGERS et al. nutzten diese Fähigkeit der Metallkomplexe, um das aktive Zentrum von Enzymen aus der Kinasefamilie optimal auszufüllen. In dieser Arbeit wurde das Design organometallischer Serinprotease-Inhibitoren enwickelt und untersucht. Das Metallzentrum hatte zum einen strukturgebende Aufgaben, zum anderen wurde auch die spezielle Reaktivität von Polypyridyl-Rutheniumkomplexen hinsichtlich ihrer Photochemie ausgenutzt. Verschiedene basische und nicht-basische Liganden wurden synthetisiert und in pseudo-oktraedrische sowie oktaedrische Metallkomplexe überführt. Aus verschiedenen basischen Komplexen wurde ein enantiomerenreiner Phenylpyridin-Iridiumkomplex mit einem IC50 für Trpysin von 1.01 μmol/L als potentester Inhibitor identifiziert. Unter Verwendung nicht-basischer Inhibitoren wurde mit einem Halbsandwichkomplex ein Inhibitor erhalten, der Thrombin mit einem IC50 von 40 μmol/L in der gleichen Größendordnung wie die basischen Amidininhibitoren hemmt. Der potenteste Inhibitor wurde unter Berücksichtigung der besonderen Reaktivität von Polypyridyl-Rutheniumkomplexen erhalten. Diese produzieren unter Belichtung Singulett Sauerstoff, der in der Lage ist bestimmte Aminosäuren unter physiologischen Bedinungen selektiv zu schädigen. Auf diese Weise konnte nach 120 min Belichtung ein Inhibitor mit einem IC50-Wert von 101 nmol/L erhalten werden.

Organometallic compounds are capable of shaping spatial globular structures by extension of the coordination number compared to organic substances. MEGGERS et al. used this capability to successfully fill in the chemical space in active sites of protein kinases. In this dissertation organometallic serine protease inhibitors were designed and examined. The metal center on one hand had structural properties to adjust the ligand sphere, but on the other hand photochemical features were used to develop CALI inhibitors (chromophore assisted light inactivation). Several basic and non-basic ligands were synthesized and transferred into metal complexes of octahedral and pseudo octahedral geometry. Out of a series of different designs of basic inhibitors an enantiomerically pure octahedral coordinated iridium phenylpyridine complex was found with an IC50 of 1.01 μmol/L for Trypsin. However, by using non-basic and less affine ligands out of a library a pseudo octahedral coordinated ruthenium cyclopentadienyl complex was identified as a Thrombin inhibitor with an IC50 of 40 μmol/L, showing no affinity for Trypsin in the studied concentration range. By using the CALI-technique where a chromophore attached to the inhibitor produces singlet oxygen the most potent inhibitors for trypsin were obtained. Several irradiation times were examined and after irradiaton for 120 min an IC50 of 101 nmol/L was determined for a bipyridine complex., Organometallische Verbindungen sind in der Lage durch Ausweitung der Koordinationszahl im Vergleich zu rein organischen Verbindungen globuläre dreidimensionale Strukturen auszubilden. MEGGERS et al. nutzten diese Fähigkeit der Metallkomplexe, um das aktive Zentrum von Enzymen aus der Kinasefamilie optimal auszufüllen. In dieser Arbeit wurde das Design organometallischer Serinprotease-Inhibitoren enwickelt und untersucht. Das Metallzentrum hatte zum einen strukturgebende Aufgaben, zum anderen wurde auch die spezielle Reaktivität von Polypyridyl-Rutheniumkomplexen hinsichtlich ihrer Photochemie ausgenutzt. Verschiedene basische und nicht-basische Liganden wurden synthetisiert und in pseudo-oktraedrische sowie oktaedrische Metallkomplexe überführt. Aus verschiedenen basischen Komplexen wurde ein enantiomerenreiner Phenylpyridin-Iridiumkomplex mit einem IC50 für Trpysin von 1.01 μmol/L als potentester Inhibitor identifiziert. Unter Verwendung nicht-basischer Inhibitoren wurde mit einem Halbsandwichkomplex ein Inhibitor erhalten, der Thrombin mit einem IC50 von 40 μmol/L in der gleichen Größendordnung wie die basischen Amidininhibitoren hemmt. Der potenteste Inhibitor wurde unter Berücksichtigung der besonderen Reaktivität von Polypyridyl-Rutheniumkomplexen erhalten. Diese produzieren unter Belichtung Singulett Sauerstoff, der in der Lage ist bestimmte Aminosäuren unter physiologischen Bedinungen selektiv zu schädigen. Auf diese Weise konnte nach 120 min Belichtung ein Inhibitor mit einem IC50-Wert von 101 nmol/L erhalten werden.

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Of 57 patients with clinically suspected mamma carcinoma 121 samples were analysed by in vitro 1H-NMR spectroscopy at 300 MHz and correlated with histological data. Within the relevant spectral region between 2.7 and 4.1 ppm strong signals were observed from fat, (phosphoryl-) choline, (phospho-) creatine, and carnitine. Furthermore, with high regularity, 8 weak, partly overlapping signals were resolved and attributed to glucose, glycine, threonine, serine, inositol, and sucrose. Their intensities were determined by an iterative fitness program. From the intensity ratios, different kinds of tissue could be distinguished based on spectroscopic criteria. Healthy or mastopathically modified tissue could be discriminated from more than 50% carcinoma affected tissue with a specificity of better than 99.5%. This fact is explained by the lower content of fatty acids in the malignant tissue. Differences between spectra of healthy of mastopathically affected tissue were only small.

A novel side reaction in Fmoc-solid-phase synthesis, which occurs during removal of protecting groups and detachment from the resin, was elucidated by investigations on model peptides: During the cleavage of Pmc- or Mtr-protecting groups from arginine residues by trifluoroacetic acid in peptides with O-tert-butyl-protected aliphatic hydroxyamino acids, peptides containing O3-sulfo-serine and O3-sulfo-threonine are formed as side-products in high yields, if suitable scavengers are absent. Subsequent to their isolation and purification, the structures of these peptide sulfuric acid mono-esters could unequivocally be proven by chemical and spectroscopic (MS, NMR, IR) methods.

Free amino acids were determined quantitatively in cerebrospinal fluid of 80 boys and 69 girls (ages 1 month-14years). On the basis of the cliniclal criterions these children were considered to be ""healthy''. The total number of examined children was 2000. Cerebrospinal fluid was mixed with an equal volume of 5% sulphosalicylic acid and the amino acids were separated by ion exchange column chromatography.1. The sexspecific investigation of the 1 month -2 years old children showed that the boys had a statistical significant hgher concentration of lysine and that no statistical significant differences existed between the groups of 2-14 years old children. 2. The age specific comparison revealed that the amino acid concentrations ofaspartic acid, citrulline, histidine, lysine, serine, threonine and tyrosine were in the cerebrospinal fluid of the younger boys statistical significant higher as compared to the older boys and that the concentration of serine in the cerebrospinal fluid of the younger girls was statistical significant higher than in the group of older girls.

Urokinase was acylated at the active site serine hydroxyl using p-amidinophenyl benzoate or p-nitrophenyl p'-guanidinobenzoate. The enzymatically inactive acyl-urokinase was reactivated in buffer (pH 7.5) or plasma at 37 degrees C with a half-life of 11 min (benzoyl-urokinase) or 10 h (p-guanidinobenzoyl-urokinase). Upon administration (50,000 IU/kg) to rabbits, urokinase was more rapidly eliminated than either acyl-enzyme. The results suggest that urokinase is eliminated via the binding to plasma inhibitors.

The mechanism of growth inhibition by D-amino acids was studied. D-Serine at concentrations from 0.02-0.2 M was sufficient to cause partial growth inhibition in seven species of bacteria representing the four most common types of peptidoglycan. The inhibited cells displayed morphological alterations. In the nucleotide-activated peptidoglycan precursors of these cells, D-alanine residues in position 4 and/or 5 of the peptide moiety were partially or even completely replaced by D-serine. The peptidoglycan also contained D-serine instead of D-alanine, but the percentual content of D-serine was significantly lower than that in the precursors. In addition, the modified peptidoglycan was less cross-linked than the normal one. Four other D-amino acids (D-threonine, D-valine, D-leucine, D-methionine) at concentrations of about 0.2 M caused similar effects as did D-serine when applied to Corynebacterium callunae and Bacillus subtilis. Thus the mode of action of D-amino acids on peptidoglycan synthesis can be generally described as follows: in their presence, at growth inhibiting concentrations modified nucleotide-activated peptidoglycan precursors are formed in which D-alanine residues are replaced by the D-amino acids. They are less efficiently incorporated into peptidoglycan. A high percentage of the modified muropeptides remains non-cross-linked, since they are poor substrates for the transpeptidation reaction. In the majority of the organisms, cross-linking was decreased when D-alanine in position 4 of the peptide subunit was replaced, in two organisms (Corynebacterium insidiosum and Staphylococcus aureus) replacement in position 5 was most effective, however. The low extent of cross-linkage is consistent with the morphological aberrations of inhibited cells. In previous studies with glycine, results were described that were in close analogy to those obtained with D-amino acids. However, glycine can replace not only D-alanine residues in position 4 and 5 but also L-alanine in position 1 of the peptide subunit.

Gas-chromatographic measurement of 18 free amino-acids from about 500 specimens of amniotic fluid between the 10th and 41st week of pregnancy. Statistical methods showed different concentrations of amino-acids in amniotic fluid during pregnancy. Serine, cysteine, methionine and tryptophane show constant concentration. Valine tyrosine and hydroxyproline continuously decrease. The other amino acids tested here show a biphasic course of concentration, falling by about 40-70% between the 10th and the 30th week after which they remain stable. Alanin, threonine, glycine and ornithine show a clear increase of concentration. This diversity of concentration of amino-acids during pregnancy hints at the importance of various factors for the composition of amniotic fluid.

Free amino acids were determined quantitatively in serum from the fasting blood of healthy children from families with patients with endemic (Balkan) nephropathy. A group of healthy children of the same age served as controls. Compared with the boys from healthy families the healthy boys from families with patients of endemic (Balkan) nephropathy had statistically significantly higher concentrations of the following amino acids: alanin, citrulline, isoleucine, leucine, ornithine, phenylalanine, proline and serine. The healthy girls from families with patients with endemic (Balkan) nephropathy had statistically significantly higher concentrations of citrulline, cystine, glycine, isoleucine, methionine, ornithine, phenylalanine, proline and serine than girls in the control group.

Two groups of four pigs each were fed ad libitum with rations containing 70.7% barley, 7.7% fish meal, 0.7% Sussopan, 0.9% mixed minerals and 20% straw meal. Group 1 received partly hydrolysed straw meal, group 2 untreated straw meal. When those rations were given, weight increase performances of 767 g per animal and day in group 1 and 537 g per animal and day in group 2 were achieved in a preliminary 30-day feeding period. On the basis ofthe weight of the feed remnants, a consumption of 19.7% dry matter of the straw meal (group 1) resp. 18,5% (group 2) of the total intake of dry matter could be ascertained. At an average live weight of 93 kg (group 1) resp. 87.5 kg (group 2) the digestibility of both rations was examined. A significant difference was only found for the crude protein fraction with an apparent digestibility of 74.6% in group 1 and of 79.1% in group 2. Those pigs which received partly hydrolysed straw meal consumed 71.4 g N per animal and day, of which 25,4% were excreted in feces and 32.4% in urine. Those animals which were fed with untreated straw meal consumed 62.9 g N per animals and day of which 20.8% were excreted in feces and 49.7% in urine. The higher N-excretion in feces could also be proved for most amino acids the feeding with partly hydrolysed straw meal. For arginine, serine, glutamic acid, proline, isoleucine and Leucine these differences were significant. Differences concerning N-retention could not be found between the groups. 25% of the organic matter of the partly hydrolysed straw meal, 9.4% of the crude fibre and 44.2% of the N-free extractives were digestible. Of the untreated straw, 12.9% of the organic matter, 5.5% ofthe crude fibres and 21.7% of the N-free extractives were digestible. 193 EFpig were calculated for partly hydrolysed and 105 EFpig for untreated straw meal per kg dry matter. The result of substracting the CaCl2 of the partly hydrolysed straw meal is 205 EFpig per kg dry matter of the straw.

A 1.6-11.8% incorporation of labelled glycine and serine into ferrichrome, ferricrocin and ferrichrysin has been achieved with four strains of Aspergillus in vivo. Cell-free extracts of Aspergillus fumigatus and A. quadricinctus capable of cyclohexa-peptide biosynthesis have been prepared.

Special attention must be paid to the formation of secondary amines as precursors of nitrosamines as a possible consequence of the fumigation of foodstuffs with ethylene oxide. Investigations carried out in vitro show that secondary amines can result in various ways by reaction of the amine groups with ethylene oxide: 1. directly, by reaction of ethylene oxide with primary amines, 2. by reaction with amino acids followed by decarboxylation. Identification of the secondary amines produced by the reaction of ethylene oxide with primary amines or amino acids was carried out by means of thin layer chromatography. In this manner, the formation of methylamino ethanol, ethylamino ethanol and diethanolamine was demonstrated by the reaction of ethylene oxide with methylamine, ethylamine and ethanolamine. Furthermore, the reaction of ethylene oxide with glycine and serine followed by decarboxylation produced, depending upon the pH value, the compounds methylamino ethanol and diethanolamine.

Concentrations of 17 free amino acids were measured in the serum of 15 healthy pregnant women at the end of pregnancy in intervals of 4--5 h. A circadian rhythm with its concentration peak at 5 p.m. could be observed for Ser, Val, Met, Ile, Leu, His, Lys and Arg. Exogenic and endogenic synchronizators are being discussed as possible causes for these fluctuations during the day. The rhythm of the free amino acids makes it necessary that only fasting blood is examined and that the time of day is always registered when the blood specimen is taken.

Amino acids constitute the main substrate of the reticulocyte. The amino acid pool of reticulocytes represents a characteristic selection. The composition of the amino acid pool is dependent on maturation. From the preferential oxidation of short-chain amino acids one would expect a ratio about of 5:1 between the oxygen consumption and ammonia formation. If one corrects for NH3-formation by the deamination of nucleotides the ratio between the oxygen consumption and NH3-formation is about an order of magnitude higher than the theoretical ratio. The small liberation of NH3 in energy production from amino acids results from the re-utilization of their alpha-NH2-group for the synthesis of serine and glycine, while the C-skeleton stems from glucose. Serine is formed via OH-pyruvate and OH-pyruvate. Serine and glycine serve preferentially for synthesis of hemoglobin. In reticulocytes there exists a compartmentation of glycine which accounts for differences between serine and glycine in isotopic experiments. From the time dependent change of the specific activities of pulse-labelled serine and glycine one may calculate that the serine synthesis amounts to 15--30% of the glucose utilization.

The results of treatment of iron deficiency anemia in 217 children and infants (aged 8 months to 12 years) with ferrosulfate serin complex are demonstrated: 208 children with simple iron deficiency anemia with hemoglobin 9.1 g/100 ml before treatment had in the first 4 weeks a daily increase of 0.082 g/10000 ml hemoglobin; in 3 children with severe anemia of chronic blood loss the daily increase was 0.21 mg/100 ml and in 6 children with hypoxic polycythemia with congenital heart disease and so called latent iron deficiency anemia the increse was 0.16 g/100 ml. Through the better absorption of this serin-ferrosulfate complex the required dosis is only 3 mg/kg/d. The benefit of this small dosis is the low rate of side effects.

Report about a very well tolerated new contrast medium Myelografin. The side-effects are being decoded and compared with the side-effects of other contrast-media for lumbar myelography. Spinal or cerebral irritating effects have never been recorded. Due to the low neurotoxicity the patient can be put in supine position immediately after the examination. Therefore the side-effects are diminished and the examination is more tolerable for the patient.

In the presence of silver carbonate-silver perchlorate and dichloromethane-toluene as solvent, 3,4,6-tri-O-acetyl-2-azido-2-deoxy-beta-D-galactopyranosyl chloride, and derivatives of L-serine and -L-serine and -L-threonine, gave, with high stereoselectivity, the benzyl esters of N-(benzyloxycarbonyl)-3-O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-alpha-D-galactopyranosyl)-L-serine (7) and -L-threonine (22), which were hydrogenolyzed and deblocked to give 3-O-(2-acetamido-2-deoxy-alpha-D-galactopyranosyl)-L-serine and -L-threonine, respectively, corresponding to the hapten of the Tn-antigen. Reduction of the azido group of 7, followed by selective O-deacetylation and benzylidenation, gave a derivative that was glycosylated with 2,3,4,6-tetra-O-acetyl-alpha-D-galactopyranosyl bromide to yield a disaccharide. A similar sequence of reactions, starting from 22, gave the L-threonine analog. Removal of the protecting groups from both compounds afforded O-beta-D-galactopyranosyl-(1 to 3)-O-(2-acetamido-2-deoxy-alpha-D-galactopyranosyl)-L-serine and -L-serine and -L-threonine, respectively, the hapten of the T-antigen.

Investigations on the role of alterations in hepatic carbohydrate metabolism in so-called pseudodiabetes of uremic subjects are reported. All experiments were carried out in acutely uremic rats produced by bilateral nephrectomy. The results are summarized in Fig. 5. From this follows that by some still unknown mechanism an altered hormonal equilibrium seems to develop. From a stimulation of endogenous hepatic proteolysis, acceleration of amino acid transport into the liver cell, and activation of L-serine-dehydratase and other key enzymes of amino acid metabolism, an increased supply of substrate for gluconeogenesis can be expected, thus leading to enhanced formation of glucose by the liver in acute uremia.

The covalent fixation of the phosphinoyl residues in the active site of alpha-chymotrypsin is proved by the application of the fluorescent phosphinoyl fluorides 1 [( 5-(dimethylamino)-1-naphthyl]phenylphosphinoyl-fluoride) or 4 [(5-methoxy-1-naphthyl)phenyl-phosphinoylfluoride]. The differences in the rates of the phosphinoylation of alpha-chymotrypsin and "methyl-alpha-chymotrypsin" as compared to 1 agree with model reactions. In both enzymes the serine-OH in the active site is phosphinoylated. The non-fluorescent 4-nitrophenyl [5-(dimethylamino)-1-naphthyl]phenylphospinate (3) and the corresponding non-fluorescent 5-methoxynaphthyl derivative 5 inhibit alpha-chymotrypsin far more slowly than the corresponding fluorides 1 and 4. The phosphinoyl residues of the nitrophenyl esters 3 and 5 are covalently linked in a yield of 80% to the active site of the enzyme with evolution of fluorescence. 20% of the nitrophenyl ester inhibits the enzyme by adsorption.

Ontogenetic changes of the activity and isoenzymes of the aminotransferases of branched chain amino acids, glycine and serine in the rat organs have been studied by quantitative histochemical method and by electrophoresis. An increase of the enzymatic activity with the 3 branched chain amino acids has been observed up to the 7th day after birth. Thereafter the changes with leucine and isoleucine are rather similar. The intensity of the specific leucine aminotransferase isoenzymes in the liver and the brain gradually increase in the development. Despite this, the nonspecific isoenzymes are available only in the embryonic and early postnatal stages. Glycine- and serine aminotransferases show relatively similar pattern of activity and more prominent change between the 7th and 14th postnatal day. The variant pattern of the aminotransferase activity in the growing rats is discussed with regard to the metabolic, structural and hormonal changes in the development. The differences in the activity of one and the same aminotransferase or its isoenzymes in the organs are most probably related to the functional differentiation.

Several inhibitors for trypsin and chymotrypsin were detected in seeds of Vicia faba by isoelectric focussing. Their isoelectric points are at pH 8.5 (main peak with shoulder), at pH 9.1 (minor peak with shoulder) and in the range of pH 9.1-6.4 (several minor peaks with significant lower activities). From the mixture of inhibitors obtained by affinity chromatography on carrier bound trypsin, three inhibitors were isolated by preparative electrophoresis in polyacrylamide gel. On electrophoresis these inhibitors behaved uniformly at pH 9.2 and at pH 4.0. Their molecular weights are about 6000 daltons. The amount of basic amino acids is high, while methionine and isoleucine are absent. Beside of trypsin and chymotrypsin some serine proteinases of microbiol origin are inhibited. The thermal stability is quite high. The Vicia inhibitors therefore differ significantly from the Phaseolus inhibitors in several properties.

Blood-borne free amino acids of 100 mothers were tested immediately after birth. Fifty of the probands had diabetes, while the other 50 were metabolically intact. Amino acid imbalance was recorded by means of multidimensional variance analysis from the diabetics and found to have been largely associated with glutamic acid threonine, alanine, glycine-serine, and glutamine.--A formula, derived from the aforementioned relevant amino acid concentrations, is given in this paper together with a nomogram (which might be used instead of the formula) for determination of diabetes-caused alterations in the amino acid spectrum

Experimental rats were fed a basal diet containing about 10% of crude protein from casein which was supplemented with 5 g DL methionine per 100 g of food. Simultaneously, either threonine, serine, glycine or glutamic acid were added in amounts of 5 gms. After a 7-day feeding period the experimental animals were injected 35S-methionine. The animals were killed after an incorporation period of 24 hrs and the 35S activity measured in different organs and in the excreta. The pattern of body weight gains, and the values for 35S activity showed that glycine had reduced the toxic action of methionine. Threonine was shown to have a similar effect while, under the prevailing conditions, serine augmented the symptoms of toxocity. Definitely higher levels of 35S activity found in the residual carcasses after methionine or serine supplementation seem to suggest an increase in cystein formation in intermediary metabolism. This, in turn, delays the elimination of SH groups from the body so that as a result of this, a higher toxocity is observed.

The wholebody retention of an 59iron-sulphate-DL-serin combination (group B) was compared to that of 59iron-sulphate in healthy female volunteers. Mean 59Fe-retention of group B(n = 9) was found to be 40% higher than that of group A(n = 10); however, this difference was mathematically statistically not significant--especially because of the high standard deviation of group B.