Novel method for l-methionine determination using l-methionine decarboxylase and application of the enzyme for l-homocysteine determination

Biosci Biotechnol Biochem. 2020 May;84(5):927-935. doi: 10.1080/09168451.2020.1715781. Epub 2020 Jan 20.

Abstract

For many years, clinical studies have suggested that blood levels of l-methionine and L-homocysteine correlate with health status or homocystinuria/hypermethioninemia. l-Methionine in a solution containing 0%, 10%, or 20% human serum was detected in 10-200 µM using l-methionine decarboxylase (MetDC). Spike and recovery tests showed that the enzymatic assay could accurately and reproducibly determine the increases in l-methionine in serum samples. These results suggest that our enzymatic method using MetDC is useful for primary screening of hypermethioninemia or homocystinuria based on serum l-methionine concentration. Additionally, we confirmed that l-methionine (100 nmol) in solution was degraded to less than the detection limit by incubation at 37ºC for 10 min using 2 U of MetDC. Therefore, l-homocysteine in serum samples can be detected with equivalent sensitivity using l-methionine γ-lyase (MGL), in solutions that either did not contain l-methionine or contained l-methionine preincubated with MetDC.Abbreviations: DTT: dithiothreitol; IPTG: isopropyl-β-d-thiogalactopyranoside; KPB: potassium phosphate buffer; MBTH: 3-methyl-2-benzothiazolinonehydrazone; mdc: the gene coding l-methionine decarboxylase; MetDC: l-methionine decarboxylase; mgl: the gene coding l-methionine γ-lyase; MGL: l-methionine γ-lyase; PLP: pyridoxal 5'-phosphate.

Keywords: L-methionine; hypermethioninemia; l-homocysteine; l-methionine decarboxylase; l-methionine γ-lyase.

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / blood
  • Amino Acid Metabolism, Inborn Errors / diagnosis
  • Carbon-Sulfur Lyases / metabolism*
  • Carboxy-Lyases / metabolism*
  • Enzyme Assays / methods*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Glycine N-Methyltransferase / blood
  • Glycine N-Methyltransferase / deficiency
  • Homocysteine / blood*
  • Homocystinuria / blood
  • Homocystinuria / diagnosis
  • Humans
  • Methionine / blood*
  • Plasmids / genetics
  • Pseudomonas putida / enzymology*
  • Pseudomonas putida / genetics
  • Spectrophotometry / methods
  • Streptomyces / enzymology*
  • Streptomyces / genetics

Substances

  • Homocysteine
  • Methionine
  • Glycine N-Methyltransferase
  • Carboxy-Lyases
  • methionine decarboxylase
  • Carbon-Sulfur Lyases
  • L-methionine gamma-lyase

Supplementary concepts

  • Hypermethioninemia