Table 1.

“Classic” metabolic intermediates that have been recognized as “signal transducers”

Metabolic intermediates	Regulatory effects
Fatty acids	Activation of PPARs,145 modulation of ion channels by palmitoylation.146
Acylcarnitines	Activation of Ca+ channels,147 induction of insulin resistance.15
Ceramides	Activation of PP2A, PKCζ → inhibition of insulin signaling,14 induction of mitochondrial and ER stress and apoptosis.148
Pyruvate	Stimulation of mitochondrial biogenesis,149 regulation of PGC−1α expression.150
Acetyl-CoA	Induction of cell growth and proliferation by promoting the acetylation of histones.151
Hexosamine	Multiple cellular effects via O-GlcNAcylation of regulatory proteins.152
NAD(P)+/NAD(P)H	Modulation of activity of metabolic enzymes, numerous additional effects via regulation of redox state and sirtuins.31, 36
ROS	Regulation of redox state, enzyme activity, high levels induce apoptosis, hypertrophy, inflammation.36, 153
AMP	Diverse effects on metabolism and cell growth through activation of AMPK.45
BCAA	Stimulation of protein synthesis154 and various additional effects via activation of mTOR and inhibition of autophagy.155

PP2A: protein phosphatase; PKC: protein kinase C; ER: endoplasmic reticulum; BCAA: branched-chain amino acids