Blood acetyl carnitine

Acyl coenzyme As are introduced into mitochondria following coenzyme A esterification in the cytoplasm. Mitochondrial entry depends upon a double membrane transport involving carnitine acyltransferases II and I. Excess acetyl CoA is used for KB synthesis. KBs are transported in the blood and ultimately metabolized via the Krebs cycle. KBs are necessary to provide energy to the brain during fasting, a true alternative substrate to glucose. 

Acetyl-L-carnitine can easily cross the blood-brain barrier, and it appears to be well tolerated and... 

D. Ketone bodies are synthesized in the liver from fatty acids derived from the blood. During the cytosolic activation of the fatty acid, ATP is converted to AMP. Carnitine is required to carry the fatty acyl group across the mitochondrial membrane. In the mitochondrion, the fatty acid is oxidized. Acetyl CoA and acetoacetyl CoA are produced and react to... 

B. After an overnight fast, fatty acids, released from adipose tissue, serve as fuel for other tissues. Carnitine is required to transport the fatty acids into mitochondria for P-oxidation. In the liver, P-oxidation supplies acetyl CoA for ketone body (acetoacetate and 3-hydroxybutyrate) synthesis. In a carnitine deficiency, blood levels of fatty acids will be elevated and ketone bodies will be low. Consequently, the body will use more glucose, so glucose levels will be decreased. 

Although the effects of insulin on postprandial metabolism are profound, other factors (e.g., substrate supply and allosteric effectors) also affect the rate and degree to which these processes occur. For example, elevated levels of fatty acids in blood promote lipogenesis in adipose tissue. Regulation by several allosteric effectors further ensures that competing pathways do not occur simultaneously for example, in many cell types fatty acid synthesis is promoted by citrate (an activator of acetyl-CoA carboxylase), whereas fatty acid oxidation is depressed by malonyl-CoA (an inhibitor of carnitine acyltransferase I activity). The control of fatty acid metabolism is described in Section 12.1. 

The rate of fatty acid oxidation is linked to the rate of NADH, FAD(2H), and acetyl CoA oxidation, and, thus, to the rate of oxidative phosphorylation and ATP utilization. Additional regulation occurs through malonyl CoA, which inhibits formation of the fatty acyl carnitine derivatives. Fatty acids and ketone bodies are used as a fuel when their level increases in the blood, which is determined by hormonal regulation of adipose tissue lipolysis. 

It may seem logical that a rise in fatty acid availability will cause an increase in the rate of fatty acid oxidation. However, the rate of oxidation of fuel is matched purely to the demand for ATP and if glucose oxidation provides sufficient ATP, the extra supply of fatty acids is not metabolized. Fatty acid oxidation can be regulated by controlling the rate at which the fatty acids enter the mitochondria, and this, in turn, is dependent on the activity of carnitine acyl transferase I. This transferase is inhibited by malonyl CoA, the production of which (by acetyl-CoA carboxylase) is stimulated by insulin. So, under conditions of hypo-insulinemia, malonyl-CoA concentrations fall and carnitine acyl transferase I is activated. This stimulates the uptake of fatty acids into the mitochondrial matrix and promotes P-oxidation. It is not so much the rise in fatty acids in the blood that stimulates P-oxidation, but the fall in insulin concentration. 

In 1990, Siliprandi et al. and Vecchiet et al. examined the effects of 2 g of oral carnitine in a single dose approximately 1 h prior to cycle ergometer exercise. Carnitine supplranmtation was reported to reduce blood lactate and increase VOj max post-exerdse. The authors claim that during this high-intensity exerdse the PDC is stimulated, thraeby reducing lactate production due to the alteration of the acetyl-CoA free CoA ratio. These findings, howevCT, were not supported, as Con-stantin-Teodosiu showed that full activity of the PDC was reached within a minute of activation and is independent of carnitine supplementation. 

Abdul Muneer PM, Alikunju S, Szlachetka AM et al (2011) Inhibitory effects of alcohol on glucose transport across the blood-brain barrier leads to neurodegeneration preventive role of acetyl-L-carnitine. Psychopharmacology 214 707-718... 

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