Aicar vs L-Carnitine (Levocarnitine)

Aicar

AICAR, also called acadesine, is 5-aminoimidazole-4-carboxamide riboside: a synthetic nucleoside, not a peptide or an amino-acid derivative. Its monophosphate, ZMP, is a natural intermediate in the pathway cells use to build purine nucleotides. AICAR became a standard laboratory tool because cells convert it to ZMP, which mimics AMP and switches on AMP-activated protein kinase (AMPK). A large body of cell and rodent work has used it to study energy sensing, glucose uptake and fatty-acid metabolism. Human clinical work has been limited and has not centred on metabolism. A known weakness of the tool is that ZMP acts on other AMP-sensitive enzymes too, so not every effect attributed to AICAR runs through AMPK.

L-Carnitine (Levocarnitine)

L-carnitine is a small quaternary ammonium compound made in the liver and kidney from the amino acids lysine and methionine. It is not a peptide, and only the L-stereoisomer is recognised by the enzymes and transporters that handle carnitine. Most carnitine in the diet comes from meat and dairy foods, and the great majority of the body's store is held in skeletal and cardiac muscle. Its biochemistry has been worked out in detail, and there is a large human research literature, including work on inherited disorders of carnitine transport. Those human studies vary widely in design and quality, and their findings are often inconsistent.

How Aicar acts

AICAR enters cells through adenosine transporters and is phosphorylated by adenosine kinase to ZMP. ZMP binds the regulatory gamma subunit of AMPK at sites that normally sense AMP, and this allosteric activation, together with increased phosphorylation of the catalytic alpha subunit, raises the kinase's activity. Activated AMPK phosphorylates targets such as acetyl-CoA carboxylase, shifting cells away from lipid synthesis and toward processes that generate ATP. ZMP accumulates to high concentrations, however, and has been reported to affect other AMP-regulated enzymes, including fructose-1,6-bisphosphatase and glycogen phosphorylase. Studies that need to separate AMPK-dependent effects often pair AICAR with genetic knockout models.

How L-Carnitine (Levocarnitine) acts

Carnitine's best-characterised role is moving long-chain fatty acids into mitochondria. Carnitine palmitoyltransferase 1 (CPT1), on the outer mitochondrial membrane, transfers the fatty acyl group from coenzyme A to carnitine; carnitine–acylcarnitine translocase carries the acylcarnitine across the inner membrane; and CPT2 on the matrix side converts it back to acyl-CoA for beta-oxidation. CPT1 is inhibited by malonyl-CoA, a control point linking fatty acid and carbohydrate metabolism. Carnitine also accepts surplus acyl groups from coenzyme A, and the acylcarnitines formed can leave the cell, which is why blood acylcarnitine profiles are used in metabolic research and screening.

The records side by side

• Type: Aicar, Nucleoside analogue; L-Carnitine (Levocarnitine), Amino acid derivative (non-peptide)
• Molecular weight: Aicar, 258.23 g/mol; L-Carnitine (Levocarnitine), 161.20 g/mol
• Molecular formula: Aicar, C9H14N4O5; L-Carnitine (Levocarnitine), C7H15NO3

Reading a comparison

A comparison places two records side by side; it does not merge them. Each description above is drawn from that compound's own record, and the two were not necessarily characterised by the same methods, at the same time, or to the same level of detail. Before comparing any attribute, it is worth establishing that both records describe the substance you think they describe — names are not identifiers, and two entries sharing a name can differ in salt form, stereochemistry or the convention used to state a mass. Where a figure carries no method beside it, the comparison is between two reported numbers rather than between two measurements.