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Table 4 Metabolite-enzyme links as identified in the DKD molecular model and description of assigned reactions and transport function

From: Serum metabolites predict response to angiotensin II receptor blockers in patients with diabetes mellitus

Metabolite-enzyme link

Description

Metabolite

Enzyme

ADMA

NOS2, NOS3

Produces nitric oxide (NOS) which is a messenger molecule with diverse functions throughout the body. In macrophages, NO mediates tumoricidal and bactericidal actions. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2

ADMA is an endogeous inhibitor of eNOS (NOS3) function

Aspargine Glutamine

ASNS

Asparagine Synthase: Adenosine triphosphate + l-Aspartic acid + l-Glutamine + Water → Adenosine monophosphate + Pyrophosphate + l-Asparagine + l-Glutamic acid

Asparagine

SLC1A1

Solute carries family member 1, l-Asp cotransporter

Glutamine

TGM2

Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins

Citrulline

NOS1, NOS2, NOS3

l-Arginine + NADPH + Oxygen → Citrulline + Nitric oxide + NADP + Water

NADPH + N-(o)-Hydroxyarginine + Oxygen + Hydrogen Ion → NADP + Nitric oxide + Citrulline + Water

l-Arginine + Oxygen + NADPH + Hydrogen Ion → Nitric oxide + Citrulline + NADP + Water

lysoPC a C16:0

lysoPC a C16:1

PC aa C36:0

PC aa C42:2

PLA2G1B

PA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides

PC aa C36:0

ATP8A1

ATP10A

PLSCR1

Transport of aminophospholipids

Tryptophan

IDO1

Catalyzes the cleavage of the pyrrol ring of tryptophan and incorporates both atoms of a molecule of oxygen