Serine metabolism in human pregnancy

Serine plays an important role in intermediary metabolism as a source of one carbon pool for nucleotide biosynthesis, as a precursor for glycine and glucose, and as a contributor to cysteine biosynthesis. A unique serine-glycine cycling between the liver and the placenta has been demonstrated in the sheep fetus. We hypothesized that, because of serine's role in growth and development, significant changes in serine metabolism will occur in pregnancy with advancing gestation. The rate of appearance (R(a)) of serine and its metabolism were quantified in healthy women longitudinally through pregnancy with a [2-(15)N(13)C]serine tracer. The contribution of serine N to urea and the rate of oxidation of serine were measured using the precursor-product relation. Plasma serine concentrations and serine R(a) were lower in pregnant (P) women, in both early and late gestation, compared with nonpregnant (NP) women [plasma serine: NP, 113 +/- 24.5; P early, 71.9 +/- 6.2; P late, 68.5 +/- 9.6 micromol/l; serine R(a): NP (n = 7), 152.9 +/- 42.8; P early (n = 12), 123.7 +/- 21.5; P late (n = 8), 102.8 +/- 18.2 micromol x kg(-1) x h(-1)]. Serine contributed approximately 6% to urea N and 15-20% to the plasma glycine pool, and oxidation of serine represented approximately 8% of R(a). There was no significant difference between P and NP subjects. Glucose infusion, at 3 mg x kg(-1) x min(-1) in P subjects, resulted in a decrease in serine R(a) and an increase in oxidation. The decrease in serine turnover in pregnancy may represent a decrease in alpha-amino nitrogen turnover related to a decreased rate of branched-chain amino acid transamination and caused by pregnancy-related hormones aimed at nitrogen conservation and accretion.     

Maturation-dependent changes of the rabbit reticulocyte energy metabolism

Rabbit reticulocytes were separated into four fractions of different maturity in order to investigate the changes of cellular respiration and glycolysis, adenine nucleotides, 2,3-biphosphoglycerate (2,3-BPG) as well as cyclic AMP level during the transition from the youngest to the most mature reticulocytes. A significant reduction of total oxygen consumption, mainly due to depression of coupled respiration was found. The decline of respiration was accompanied by a 2-fold increase of the rate of aerobic glycolysis indicating a reduced Pasteur effect during maturation. A decline of ATP and an increase of ADP concentration was found. The oxygen-delivery capacity of the red cells increased by about 26% caused by an increase of the 2,3-BPG level of about 2 mmol/l cells. Cyclic AMP level in the fraction of youngest reticulocytes was about 60-fold higher than that in mature rabbit erythrocytes. The biggest decline of cyclic AMP was registered during the transition from youngest to the intermediate stage of maturity.     

Serine metabolism in legume nodules: Purification and properties of phosphoserine aminotransferase

Plant cells excrete protons via an electrogenic proton pump, the K⁺-stimulated, Mg²⁺-dependent H⁺-ATPasc, located on the cytoplasmic side of the plasma membrane. Plasma membrane redox reactions are also coupled to proton excretion. Various inhibitors were used on carrot ( Daucus carola L.) cells in an attempt to distinguish between the two processes. Inhibitors of electron transport reactions in the plasma membrane (chloroquine, 8-hydroxyquinolinc, 4,7-dichloroquinolinc and retinoic acid) inhibited ferricyanide-induced proton excretion by 37–100%, while they inhibited potassium ferricyanide reduction, a measure of plasma membrane redox activity, by 42–100%. The above-mentioned quinolines and retinoic acid inhibited cell growth by 49–98%, with the exception of chloroquine, which stimulated carrot cell growth by 36%.     

Transferrin in the reticulocyte cytosol

Radioactive iodine-labeled iron-saturated human transferrin was shown to enter the cytosol of rabbit reticulocytes but not erythrocytes, and to be combined therein with a small “carrier” material not identical to the membrane transferrin receptor.     

Glycine Serine Interconversion in the Rooster

Serine was isolated by the column chromatography from the hydrolyzates of proteins of the serum, the liver and the pectoral muscle which were obtained from the roosters fed a diet containing 2-¹⁴C glycine for 16–17 days. The carbon chain of serine was cut off by treating with sodium periodate. The specific activity of each carbon (as barium carbonate) was estimated. Carboxyl carbon had little radioactivity. The specific activity of hydroxymethyl carbon was 10–19% of that of methylen carbon. Glycine isolated from the same hydrolyzates was degraded by ninhydrin oxidation. Formaldehyde produced from 2-C was oxidized to carbon dioxide by treating with mercuric chloride. Carboxyl carbon had little radioactivity. The specific activities of 2-C of glycine and 2-C of serine in the same tissue protein were compared. The ratio of serine 2-C/glycine 2-C was between 0.7 – 1.5. These results seem to indicate that glycine directly converts to serine in the rooster. The quantitative significance of the pathways of glycine (serine) biosynthesis is discussed.     

Evidence for the Involvement of Serine Transhydroxymethylase in Serine and Glycine Interconversions in SALMONELLA TYPHIMURIUM

Salmonella typhimurium can normally use glycine as a serine source to support the growth of serine auxotrophs. This reaction was presumed to occur by the reversible activity of the enzyme, serine transhydroxymethylase (E. C. 2. 1. 2. 1; L-serine: tetrahydrofolic-5, 10 transhydroxymethylase), which is responsible for glycine biosynthesis. However, this enzyme had not been demonstrated to be solely capable of synthesizing serine from glycine in vivo. The isolation and characterization of a mutant able to convert serine to glycine but unable to convert glycine to serine supports the conclusion that a single enzyme is involved in this reversible interconversion of serine and glycine. The mutation conferring this phenotype was mapped with other mutations affecting serine transhydroxymethylase (glyA) and assays demonstrated reduced activities of this enzyme in the mutant.     

Initiation reactions in the mRNA-dependent reticulocyte lysate

Reticulocyte lysates depleted of mRNA by digestion with micrococcal nuclease still show an unexpectedly high rate of formation of 80 S initiation complexes. Formation of these complexes is sensitive to all inhibitors of the normal protein synthesis initiation process tested. Such lysates contain high concentrations of mRNA fragments which can be utilized for initiation, with which exogenous mRNA must compete. As a consequence of this competition, mRNAs that are weak initiators may be translated poorly by this system even at low exogenous mRNA concentrations.