Propionyl-L-carnitine: Biochemical significance and possible role in cardiac metabolism

Abstract

Propionyl-CoA is formed principally during amino acid catabolism. It is then converted chiefly to succinate in a described three-step sequence. Free propionate is formed from propionyl-CoA to a very limited extent, but this anion can participate in a futile cycle of activation and hydrolysis, which can significantly deplete mitochondrial ATP. Free CoA and propionyl-CoA cannot enter or leave mitochondria, but propionyl groups are transferred between separate CoA pools by prior conversion to propionyl-L-carnitine. This reaction requires carnitine and carnitine acetyl transferase, an enzyme abundant in heart tissue. Propionyl-L-carnitine traverses both mitochondrial and cell membranes. Within the cell, this mobility helps to maintain the mitochondrial acyl-CoA/CoA ratio. When this ratio is increased, as in carnitine deficiency states, deleterious consequences ensue, which include deficient metabolism of fatty acids and urea synthesis. From outside the cell (in blood plasma), propionyl-L-carnitine can either be excreted in the urine or redistributed by entering other tissues. This process apparently occurs-without prior hydrolysis and reformation. It is suggested that heart tissue utilizes such exogenous propionyl-L-carnitine to stimulate the tricarboxylic acid cycle (via succinate synthesis) and that this may explain its known protective effect against ischemia.

Changes in skeletal muscle histology and metabolism in patients undergoing exercise deconditioning: Effect of propionyl-L-carnitine

“…In effect, within the mitochondria, PLC is readily converted into free carnitine and propionyl CoA. 25 The increase in glycogen muscle content may be related to the metabolic action of propionyl-CoA rather than to the increased availability of free carnitine. In fact, an equimolar dose of L-carnitine increased free carnitine muscle content, but did not modify glycogen levels.…”

“…Propionyl-CoA may increase glycogen muscle content either by promoting glycogen synthesis or by blocking its utilization. In effect, propionyl-CoA is a gluconeogenic substrate, 25 and thus it can generate glucose-6-phosphate, which can become glycogen. Alternatively, propionyl-CoA, by entering into the Krebs' cycle as succinyl-CoA, 25 could provide additional substrates for energy metabolism through an anaplerotic mechanism 21 and thus lead to a glycogen sparing effect.…”

Insulin Exposure and Unifying Aging

“…Free radical damage in rodent heart ischemia/reperfusion model systems can be prevented by pretreatment (but not postischemic treatment) [44]) with ALCAR or the more efficiently transported [45] propionylcarnitine at 10-mM levels [46,47]. The huge reperfusion elevation of free radical damage is always proceeded by profound 10-25% decreases in cardiolipin levels [48][49][50][51] and 20-60% reduced magnitude of state 3 energy production capabilities [48,52] during the ischemic period which experiences little elevation of free radical damage.…”

“…Unlike the membrane-stabilizing and cardiolipin level elevation properties of ALCAR and other short-chain acylCAR [74] that improve mitochondrial function, higher levels of the long acyl chain carnitines destabilize membranes and must be catabolized or exchanged out of vigorously exercising muscle cells to avoid high (toxic) levels [75].…”

Preventive cytoprotection in social diseases

“…Комбинированный метаболический препарат, со-держащий в себе L-карнитин и пропионат, в условиях клеточной и тканевой гипоксии, вызванной ишемией ми-окарда, помогает осуществлению энергетических процес-сов цикла трикарбоновых кислот (цикла Кребса) за счет легко метаболизируемого пропионата, который быстро трансформируется в сукцинат, не требуя дополнительно-го энергообеспечения [15].…”