Fig. 1 Regulation of the intracellular spermidine pool.

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Fig. 1 Regulation of the intracellular spermidine pool. Regulation of the intracellular spermidine pool. Major routes and enzymes of mammalian polyamine metabolism. The cytosolic spermidine pool results from uptake, biosynthesis, catabolism, and transport. Spermidine is formed from its precursor putrescine or by degradation from spermine. Polyamine biosynthesis connects to arginine and NO metabolism via ornithine (as part of the urea cycle). Spermidine catabolism is mainly mediated through acetylation and subsequent oxidation reactions. Through the cofactors dcSAM (polyamine biosynthesis) and acetyl-CoA (polyamine catabolism), polyamine metabolism interrelates to protein/DNA methylation and protein acetylation, respectively, and thus indirectly influences epigenetic regulation of gene expression. ACLY, ATP-citrate synthase; ACSS2, acetyl-coenzyme A synthetase, cytoplasmic; AMD1, S-adenosylmethionine decarboxylase proenzyme; ARG1, arginase-1; ATP, adenosine triphosphate; CoA, coenzyme A; dcSAM, decarboxylated S-adenosylmethionine; MAT1/2A, S-adenosylmethionine synthase isoform type 1/2; NAA, N-acetylaspartate; NAT8L, N-acetylaspartate synthetase; NO, nitric oxide; ODC1, ornithine decarboxylase; PAOX, peroxisomal N(1)-acetyl-spermine/spermidine oxidase; SAM, S-adenosylmethionine; SMO, spermine oxidase; SAT1, spermidine/spermine N(1)-acetyltransferase 1; SMS, spermine synthase; Spd, spermidine; Spm, spermine SRM, spermidine synthase; VPAT, vesicular polyamine transporter. Frank Madeo et al. Science 2018;359:eaan2788 Copyright © 2018, The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works