Anesthetic management of patients with carnitine deficiency or a defect of the fatty acid β-oxidation pathway

Abstract

Carnitine is essential for the transport of long-chain fatty acids from the cytoplasm to the mitochondrial matrix. The carnitine shuttle transports long-chain fatty acylcarnitine to the mitochondrial matrix. Subsequently, long-chain fatty acyl CoA, which is split from long-chain fatty acylcarnitine by carnitine palmitoyltransferase II, undergoes fatty acid β-oxidation. Acetyl CoA is produced from long-chain fatty acyl CoA via fatty acid β-oxidation and aids in the synthesis of adenosine triphosphate via the tricarboxylic acid cycle and electron transport chain. In addition, in the fasting state, it leads to ketone body production in the liver and glucose production via gluconeogenesis. However, patients with compromised fatty acid β-oxidation, owing to carnitine deficiency as well as defects in carnitine transport and the fatty acid β-oxidation pathway, develop hypoglycemia, cardiomyopathy, arrhythmia, and hypotonia. These conditions are attributed to the accumulation of released fatty acids and acylcarnitine. This review aimed to shed light on the anesthetic management of patients with compromised fatty acid β-oxidation undergoing various surgeries by assessing relevant case reports associated with fatty acid β-oxidation disorder in PubMed. Pre-anesthetic and intraoperative evaluation should include monitoring of glucose and carnitine levels and specific cardiac tests, such as echocardiography. Considering that propofol is dissolved in 10% long-chain fatty acids, propofol infusion should be avoided because of increased long-chain fatty acid loading in patients with compromised fatty acid β-oxidation. Thus, anesthesia using opioids (remifentanil and fentanyl), midazolam, dexmedetomidine, etomidate, and non-depolarizing neuromuscular blocking agents would be appropriate in such patients.

Lipid metabolism reprogramming in colorectal cancer

“…The origin of human FAs includes three metabolic pathways; de novo synthesis of FAs, exogenous FA uptake, and degradation of FAO. The de novo synthesis of FAs relies on enzymes such as ATP citrate lyase (ACLY), acetyl‐CoA carboxylase (ACC), FA synthase (FASN), and stearoyl‐CoA desaturase (SCD) 15 . However, in CRC cells, FASN, SCD, ACLY, and the key enzyme carnitine palmitoyltransferase (CPT1) in the FAO process are all upregulated, thereby promoting the production of FAs to provide the material basis for the growth of CRC cells 16 .…”

“…The de novo synthesis of FAs relies on enzymes such as ATP citrate lyase (ACLY), acetyl-CoA carboxylase (ACC), FA synthase (FASN), and stearoyl-CoA desaturase (SCD). 15 However, in CRC cells, FASN, SCD, ACLY, and the key enzyme carnitine palmitoyltransferase (CPT1) in the FAO process are all upregulated, thereby promoting the production of FAs to provide the material basis for the growth of CRC cells. 16 Furthermore, when the expression of FA de novo synthase (FASN) is inhibited, it was surprisingly found that CRC cells still grew at a non-attenuating rate due to intake of exogenous FAs that ensured their survival.…”

Mechanisms underlying lipid emulsion resuscitation for drug toxicity: a narrative review

“…However, currently, LE is additionally used as solvent of propofol and etomidate, and treatment of drug toxicity including LAST. Long-chain fatty acid is transported to cardiac mitochondria from cytoplasm using following three steps, and subsequently used to produce adenosine triphosphate (ATP) [7]. Long-chain fatty acyl-CoA is produced from long-chain fatty acid by long-chain fatty acyl-CoA synthase in cytoplasm [7].…”

“…Long-chain fatty acid is transported to cardiac mitochondria from cytoplasm using following three steps, and subsequently used to produce adenosine triphosphate (ATP) [7]. Long-chain fatty acyl-CoA is produced from long-chain fatty acid by long-chain fatty acyl-CoA synthase in cytoplasm [7]. First, This article is protected by copyright of Korean Journal of Anesthesiology.…”

“…All rights reserved. long-chain fatty acylcarnitine is produced from long-chain fatty acyl-CoA and carnitine in the cytoplasm by carnitine palmitoyltransferase I [7]. Second, long-chain fatty acylcarnitine is transported from cytoplasm to cardiac mitochondria by carnitine acylcarintine translocase [7].…”