Transport of Fatty Acids into the Mitochondria
A fatty acid is first activated to acyl-CoA with ATP and CoA-SH (coenzyme A/ active vitamin B5). In order to poduce energy from the fatty acid, it needs to be metabolized in the β-oxidation or fatty acid oxidation inside the mitochondria. Short-chained fatty acids can pass into the mitochondria, but longer fats (long-and middle-chained fatty acids) need to bind to carnitine to enter the mitochondria:
Acyl-CoA + Carnitine -> Acyl-carnitine + CoA-SH
(enzyme: carnitine palmitoyltransferase)
Acyl-carnitine is transported into the mitochondria where carnitine is released and CoA-SH binds to the fatty acid to form Acyl-CoA again.
In the β-oxidation acetyl-CoA is broken down from the end of the long fatty acid chain. Apart from CoA-SH this requires FAD (active vitamin B2) and NAD+ (active vitamin B3), which are converted to FADH2 and NADH/H+. CoA-SH is bound in acetyl-CoA.
Can Stimulate the Pyruvate Dehydrogenase
Carnitine can bind to acetyl-CoA to form acetyl-carnitine and CoA-SH and this can increase the function of the pyruvate dehydrogenase (1). The pyruvate dehydrogenase is inhibited by high levels of acetyl-CoA, NADH or ATP and needs coenzyme A/CoA-SH as a cofactor. Carnitine binds acetyl-CoA, which reduces acetyl-CoA and increases CoA-SH and this stimulates the pyruvate dehydrogenase.
Carnitine and the Thyroid
Carnitine has an antagonistic effect on thyroid action. It can block the entry of triiodothyronine (T3) and thyroxine (T4) into the cell nuclei (2) and has been shown to have beneficial effects on serious hyperthyroidism.
Thyroid hormones in turn also seem to influence carnitine metabolism (3) and carnitine palmitoyltransferase activity is increased 3-4 fold in hyperthyroid rats, compared to hypothyroid rats (4).
L-carnitine can act as a calcium chelator and reduce free calcium levels (5).
Carnitine Biosynthesis and Supplements:
The body can synthesize carnitine from the amino acid lysine with S-adenosylmethionine and dependent on other cofactors like iron, vitamin C and vitamin B3.
Supplement forms of carnitine are carnitine tartrate, carnitine fumarate and acetyl-carnitine.
Acetyl-carnitine is a form that differs from carnitine found in foods a lot, because it contains acetyl-. This is thought to stimulate the energy metabolism by supporting the formation of acetyl-CoA.
Because acetyl-CoA already has acetyl- bound, it cannot bind any more acetyl-CoA like shown in the picture above. Binding acetyl-CoA and stimulating the pyruvate dehydrogenase might be an important function of carnitine, which acetyl-carnitine cannot fulfill. This could be a disadvantage of taking acetyl-carnitine over L-carnitine.
I prefer carnitine tartrate at the moment with doses up to 500mg. Normal diets contain 20-200mg carnitine and the body can synthesize 11-34mg daily. Carnitine is found in many foods and levels are by far the highest in red meats (6,7).
I’ve had mixed reactions to carnitine in the past.
Update: Currently not taking carnitine, it seemed to induce too much calcium deficiency. I’ll try supporting methylation, like with B2 and hydroxoB12, maybe that can support carnitine biosynthesis.
Carnitine stimulation of pyruvate dehydrogenase complex (PDHC) in isolated human skeletal muscle mitochondria.
Effects of carnitine on thyroid hormone action.
Urinary excretion of carnitine in patients with hyperthyroidism and hypothyroidism: Augmentation by thyroid hormone
The outer carnitine palmitoyltransferase and regulation of fatty acid metabolism in rat liver in different thyroid states
L-carnitine is a calcium chelator: a reason for its useful and toxic effects in biological systems