The mouse Gm853 gene encodes a novel enzyme: Leucine decarboxylase

TY - JOUR

T1 - The mouse Gm853 gene encodes a novel enzyme

T2 - Leucine decarboxylase

AU - Lambertos, Ana

AU - Ramos-Molina, Bruno

AU - Cerezo, David

AU - López-Contreras, Andrés J.

AU - Peñafiel, Rafael

PY - 2018/3

Y1 - 2018/3

N2 - Ornithine decarboxylase (ODC) is a key enzyme in the biosynthesis of polyamines. ODC-antizyme inhibitors (AZINs) are homologous proteins of ODC, devoid of enzymatic activity but acting as regulators of polyamine levels. The last paralogue gene recently incorporated into the ODC/AZINs family is the murine Gm853, which is located in the same chromosome as AZIN2, and whose biochemical function is still unknown. By means of transfection assays of HEK293T cells with a plasmid containing the coding region of Gm853, we show here that unlike ODC, GM853 was a stable protein that was not able to decarboxylate L-ornithine or L-lysine and that did not act as an antizyme inhibitor. However, GM853 showed leucine decarboxylase activity, an enzymatic activity never described in animal cells, and by acting on L-leucine (Km = 7.03 × 10− 3 M) it produced isopentylamine, an aliphatic monoamine with unknown function. The other physiological branched-chain amino acids, L-valine and L-isoleucine were poor substrates of the enzyme. Gm853 expression was mainly detected in the kidney, and as Odc, it was stimulated by testosterone. The conservation of Gm853 orthologues in different mammalian species, including primates, underlines the possible biological significance of this new enzyme. In this study, we describe for the first time a mammalian enzyme with leucine decarboxylase activity, therefore proposing that the gene Gm853 and its protein product should be named as leucine decarboxylase (Ldc, LDC).

AB - Ornithine decarboxylase (ODC) is a key enzyme in the biosynthesis of polyamines. ODC-antizyme inhibitors (AZINs) are homologous proteins of ODC, devoid of enzymatic activity but acting as regulators of polyamine levels. The last paralogue gene recently incorporated into the ODC/AZINs family is the murine Gm853, which is located in the same chromosome as AZIN2, and whose biochemical function is still unknown. By means of transfection assays of HEK293T cells with a plasmid containing the coding region of Gm853, we show here that unlike ODC, GM853 was a stable protein that was not able to decarboxylate L-ornithine or L-lysine and that did not act as an antizyme inhibitor. However, GM853 showed leucine decarboxylase activity, an enzymatic activity never described in animal cells, and by acting on L-leucine (Km = 7.03 × 10− 3 M) it produced isopentylamine, an aliphatic monoamine with unknown function. The other physiological branched-chain amino acids, L-valine and L-isoleucine were poor substrates of the enzyme. Gm853 expression was mainly detected in the kidney, and as Odc, it was stimulated by testosterone. The conservation of Gm853 orthologues in different mammalian species, including primates, underlines the possible biological significance of this new enzyme. In this study, we describe for the first time a mammalian enzyme with leucine decarboxylase activity, therefore proposing that the gene Gm853 and its protein product should be named as leucine decarboxylase (Ldc, LDC).

KW - Amino acid decarboxylases

KW - AZIN2 paralogue

KW - Enzyme catalysis

KW - Gm853

KW - Isopentylamine

KW - Ornithine decarboxylase antizyme inhibitor

KW - Polyamine

KW - Protein evolution

KW - Testosterone

U2 - 10.1016/j.bbagen.2017.11.007

DO - 10.1016/j.bbagen.2017.11.007

M3 - Journal article

C2 - 29108956

AN - SCOPUS:85036513252

SN - 0304-4165

VL - 1862

SP - 365

EP - 376

JO - Biochimica et Biophysica Acta - General Subjects

JF - Biochimica et Biophysica Acta - General Subjects

IS - 3

ER -