Targets | Metabolic pathway | Activity | Drugs: inhibitors or activators | References |
---|---|---|---|---|
1 | Proteolysis/alanine/transaminase/pyruvate | increased |
aminooxacetic, 2PAM, D alanine, β chloro-L-alanine | [42, 43] |
2 |
Lactate dehydrogenase/pyruvate/lactate/NAD+ Malate dehydrogenase/OAA/malate/NAD+ Malic enzyme/malate/pyruvate/lactate/NAD+ |
increased
increased increased |
Br pyruvate, gossypol D malate, humic acid D malate | [44–46] |
3 | Glycolysis | increased | mannoheptulose, lodinamineepalresta, citrate | [47–49] |
4 |
PEP carboxykinase/PEP/OAA Pyruvate carboxylase/pyruvate/OAA |
increased
decreased |
Cl-PEP, β sulphopyruvate 3-hydroxybutyrate (ketone bodies will activate) |
[50, 51] [52] |
5 |
Pyruvate kinase (M2 bottleneck)/PEP/pyruvate Pyruvate dehydrogenase/pyruvate/acetylCoA |
decreased
decreased |
dihydroxyphenylethanol, polyethylene - glycol lipoic acid, kinase inhibitors (dichloroacetate, 2-chloropropionate) or PP2A agonists (xylulose5P, B12, choline) |
[53–55] [16, 17] |
6 |
Lipolytic fatty acid source of acetyl CoA Carnitine transporter | increased |
niacine, Growth hormone inhibitors Avoid oxfenicine or levofloxacin | [56, 57] |
7 | Citrate synthase (OAA+ acetylCoA)/citrate | increased |
Dserine, fluoroacetylCoA, carboxymethyl-CoA, citrate (via product inhibition), capsaicine (via electron transport inhibition and NADH increase) | [13] |
8 |
ATPcitrate lyase citrate/OAA+acetylCoA Triglycerides synthesis via acetyl CoA Other OAA sources |
increased
increased increased |
hydroxycitrate, fluorocitrate xanthohumol (removes triglycerides) D malate |
[58] [59] |
9 |
Choline dehydrogenase/methylation/lipotropic Choline kinase/phosphorylcholine/lecithin |
decreased
increased |
choline miltefosin, farnesol | [60, 61] |
10 | PP2A methylation (it counteracts signaling and enzyme kinases) | decreased | betaine, folate, B12, trimethylglycine (via SAM) | |
11 | Histone deacetylase (gene silencing) | increased | butyrate, valproate, benzamide, trichostatin | [62] |
12 |
Cytochrome P450 demethylase (hypomethylated promoters)HAT/hexokinase expression Histone acetylase |
increased
increased |
ketonazole, bergamottin, quinine anacardic acid, garcinol, curcumine |
[63–67] [66, 67] |
13 | Tyrosine kinase-signaling route (MAP kin, PI3 kin, PLCγ) | increased | imatinib mésilate (glivec chemotherapy) | |
14,15, 16 |
GH-IGF IGFBP |
increased
decreased |
octreotide, pegvisomant apigenin, casodex, omeprazol | [68–70] |
17 | Arginine dependency | increased |
arginine deprivation diet, pegylated arginine deiminase |
[18–20] [71–73] |
18 | Arginase/arginine/ornithine | increased | norvaline, N-omega-hydroxy-nor-arginine, boroargininre | [74–76] |
19 |
Polyamine pathway: Ornithine decarboxylase/putrescine SAM decarboxylase | increased |
DFMO (2-difluoromethylornithine), MGBG methylglyoxal bis (guanylhydrazone), 4-amidinoindan-1one-2'-amidinhydrazone(alfa-fluoromethylhistidine) | [77–79] |
20 | Glutaminase/glutamate | increased |
DON(6-diazo-5-oxo-l-norleucine), riluzole, naftazone | [80]. |
21 | Argininosuccinate synthetase | decreased | troglitazone | [81] |