Publications

• Characterization of a defect in the pathway for converting 5'-deoxy-5'-methylthioadenosine to methionine in a subline of a cultured heterogeneous human colon carcinoma.

  Ghoda L.Y., Savarese T.M., Dexter D.L., Parks R.E. Jr., Trackman P.C., Abeles R.H.

  5'-Deoxy-5'-methylthioadenosine (methylthioadenosine) is cleaved to adenine and 5-methylthioribose-1-phosphate (methylthioribose-1-P). Methylthioribose-1-P is converted to 2-keto-4-methylthiobutyrate ( ketomethylthiobutyrate ) which is transaminated to methionine. We report that one subline of a h ... >> More

  5'-Deoxy-5'-methylthioadenosine (methylthioadenosine) is cleaved to adenine and 5-methylthioribose-1-phosphate (methylthioribose-1-P). Methylthioribose-1-P is converted to 2-keto-4-methylthiobutyrate ( ketomethylthiobutyrate ) which is transaminated to methionine. We report that one subline of a heterogeneous human colon carcinoma, DLD-1 Clone D, only forms methylthioribose-1-P from methylthioadenosine or 5'-deoxy-5'-methylthioinosine (methylthioinosine), a deaminated derivative of methylthioadenosine, whereas Clone A converts methylthioadenosine and methylthioinosine to methionine, as shown by growth studies in culture of Clone A and Clone D cells and radioactive studies utilizing [methyl-14C]methylthioadenosine or [methyl-14C]methylthioinosine in the presence of extracts of these cells lines. To characterize this defect, we utilized three protein fractions isolated from rat liver which together convert methylthioribose-1-P to ketomethylthiobutyrate . Addition of only Fraction A to Clone D sonicates restores its ability to convert methylthioadenosine to methionine. This fraction is responsible for converting methylthioribose-1-P to 5-methylthioribulose -1-phosphate; radioactive studies confirm this observation. Thus, Clone D is deficient in an enzyme contained in Fraction A; this represents a qualitative biochemical difference between the two clones derived from a single human tumor. << Less

  J Biol Chem 259:6715-6719(1984) [PubMed] [EuropePMC]

• Methionine synthesis from 5'-S-Methylthioadenosine. Resolution of enzyme activities and identification of 1-phospho-5-S methylthioribulose.

  Trackman P.C., Abeles R.H.

  5'-S-Methylthioadenosine is converted to methionine in mammalian systems, microorganisms and plants. 5'-S-Methylthioadenosine is first converted to 1-phospho-5-S-methylthioribofuranoside (1-PMTR) which is then converted to 2-keto-4-S-methylthiobutyrate, the precursor of methionine. We have now inv ... >> More

  5'-S-Methylthioadenosine is converted to methionine in mammalian systems, microorganisms and plants. 5'-S-Methylthioadenosine is first converted to 1-phospho-5-S-methylthioribofuranoside (1-PMTR) which is then converted to 2-keto-4-S-methylthiobutyrate, the precursor of methionine. We have now investigated the conversion of 1-PMTR to the keto acid. This conversion requires at least three protein fractions designated A, B, and C. Fraction A catalyzes an isomerization of 1-PMTR to form 1-phospho-5-S-methylthioribulose. The identification of this compound is based in part on the products obtained after NaIO4 oxidation, i.e. S-methylthioacetaldehyde, formate, and phosphoglycolic acid. When fractions A and B are added to 1-PMTR, two additional compounds, designated II and III, were detected. No O2 was consumed in the formation of compounds II and III. These compounds are, therefore, at the oxidation state of 5-S-methylthioribose. Compound II is phosphorylated as evidenced by its electrophoretic behavior before and after alkaline phosphatase treatment. Addition of fraction C to compounds II and III leads to O2 consumption and to the conversion of these compounds to 2-keto-4-S-methylthiobutyrate. Thus, compounds II and III are precursors of the keto acid. These compounds have not been fully characterized. << Less

  J Biol Chem 258:6717-6720(1983) [PubMed] [EuropePMC]

• Intermediates in the conversion of 5'-S-methylthioadenosine to methionine in Klebsiella pneumoniae.

  Furfine E.S., Abeles R.H.

  Extracts of Klebsiella pneumoniae oxidatively convert 1-phospho-5-S-methylthioribose (1-PMTR) to alpha-keto-gamma-methylthiobutyrate, a precursor of methionine, and to S-methylthiopropionate and formate. One equivalent of formate is produced per equivalent of alpha-keto-gamma-methylthiobutyrate an ... >> More

  Extracts of Klebsiella pneumoniae oxidatively convert 1-phospho-5-S-methylthioribose (1-PMTR) to alpha-keto-gamma-methylthiobutyrate, a precursor of methionine, and to S-methylthiopropionate and formate. One equivalent of formate is produced per equivalent of alpha-keto-gamma-methylthiobutyrate and two equivalents of formate per equivalent of methylthiopropionate. Two compounds were identified as intermediates in this reaction sequence: 1-phospho-5-S-methylthioribulose (1-PMT-ribulose) and 1-phospho-2,3-diketo-5-S-methylpentane. The enzyme, 1-PMTR isomerase, which converts 1-PMTR to 1-PMT-ribulose was highly purified. In addition, a protein fraction was isolated which converts 1-PMT-ribulose to the phosphodiketone. A second protein fraction was isolated that converts the phosphodiketone to an intermediate which has not been isolated so far. This intermediate is oxidatively converted to alpha-keto-gamma-methylthiobutyrate and S-methylthiopropionate by a third protein fraction. Methylthiopropionate is not derived from free alpha-keto-gamma-methylthiobutyrate. << Less

  J Biol Chem 263:9598-9606(1988) [PubMed] [EuropePMC]

  This publication is cited by 2 other entries.

• <i>Escherichia coli</i> possessing the dihydroxyacetone phosphate shunt utilize 5'-deoxynucleosides for growth.

  Huening K.A., Groves J.T., Wildenthal J.A., Tabita F.R., North J.A.

  All organisms utilize <i>S</i>-adenosyl-l-methionine (SAM) as a key co-substrate for the methylation of biological molecules, the synthesis of polyamines, and radical SAM reactions. When these processes occur, 5'-deoxy-nucleosides are formed as byproducts such as <i>S</i>-adenosyl-l-homocysteine, ... >> More

  All organisms utilize <i>S</i>-adenosyl-l-methionine (SAM) as a key co-substrate for the methylation of biological molecules, the synthesis of polyamines, and radical SAM reactions. When these processes occur, 5'-deoxy-nucleosides are formed as byproducts such as <i>S</i>-adenosyl-l-homocysteine, 5'-methylthioadenosine (MTA), and 5'-deoxyadenosine (5dAdo). A prevalent pathway found in bacteria for the metabolism of MTA and 5dAdo is the dihydroxyacetone phosphate (DHAP) shunt, which converts these compounds into dihydroxyacetone phosphate and 2-methylthioacetaldehyde or acetaldehyde, respectively. Previous work in other organisms has shown that the DHAP shunt can enable methionine synthesis from MTA or serve as an MTA and 5dAdo detoxification pathway. Rather, the DHAP shunt in <i>Escherichia coli</i> ATCC 25922, when introduced into <i>E. coli</i> K-12, enables the use of 5dAdo and MTA as a carbon source for growth. When MTA is the substrate, the sulfur component is not significantly recycled back to methionine but rather accumulates as 2-methylthioethanol, which is slowly oxidized non-enzymatically under aerobic conditions. The DHAP shunt in ATCC 25922 is active under oxic and anoxic conditions. Growth using 5-deoxy-d-ribose was observed during aerobic respiration and anaerobic respiration with Trimethylamine N-oxide (TMAO), but not during fermentation or respiration with nitrate. This suggests the DHAP shunt may only be relevant for extraintestinal pathogenic <i>E. coli</i> lineages with the DHAP shunt that inhabit oxic or TMAO-rich extraintestinal environments. This reveals a heretofore overlooked role of the DHAP shunt in carbon and energy metabolism from ubiquitous SAM utilization byproducts and suggests a similar role may occur in other pathogenic and non-pathogenic bacteria with the DHAP shunt.<h4>Importance</h4>The acquisition and utilization of organic compounds that serve as growth substrates are essential for <i>Escherichia coli</i> to grow and multiply. Ubiquitous enzymatic reactions involving S-adenosyl-l-methionine as a co-substrate by all organisms result in the formation of the 5'-deoxy-nucleoside byproducts, 5'-methylthioadenosine and 5'-deoxyadenosine. All <i>E. coli</i> possess a conserved nucleosidase that cleaves these 5'-deoxy-nucleosides into 5-deoxy-pentose sugars for adenine salvage. The DHAP shunt pathway is found in some extraintestinal pathogenic <i>E. coli</i>, but its function in <i>E. coli</i> possessing it has remained unknown. This study reveals that the DHAP shunt enables the utilization of 5'-deoxy-nucleosides and 5-deoxy-pentose sugars as growth substrates in <i>E. coli</i> strains with the pathway during aerobic respiration and anaerobic respiration with TMAO, but not fermentative growth. This provides an insight into the diversity of sugar compounds accessible by <i>E. coli</i> with the DHAP shunt and suggests that the DHAP shunt is primarily relevant in oxic or TMAO-rich extraintestinal environments. << Less

  Microbiol Spectr 12:e0308623-e0308623(2024) [PubMed] [EuropePMC]

  This publication is cited by 3 other entries.