Encephalopathies brain energy metabolism

Mahoney CA, Samacki P Arieff Al. (1984). Uremic encephalopathy Role of brain energy metabolism. Am J Physiol 247 (Reneil Fluid Electrolyte Physiol. 16), F527-F532. 

Defects of energy metabolism cause profound disturbances in the function of muscle and brain. Such defects may present as a myopathy, encephalopathy or encephalo-myopathy. Clinical features are best appreciated by understanding the preferred oxidizable substrates for brain and muscle. 

Rao K. V. and Norenberg M. D. (2001). Cerebral energy metabolism in hepatic encephalopathy and hyperammonemia. Metab Brain Dis. 16 67-78. 

The brain has an absolute dependence on the blood for its immediate supply of oxygen and energy substrates. Interruption of oxygen or substrate supply by compromise of pulmonary or cardiovascular function or metabolic factors results in encephalopathy and, if prolonged, neuronal cell death. The brain uses approximately 20% of the total oxygen supply of the body. While glucose remains the primary energy substrate for the brain, alternative substrates maybe used under certain circumstances (see Ch. 31). 

Primary carnitine deficiency is caused by a deficiency in the plasma-membrane carnitine transporter. Intracellular carnitine deficiency impairs the entry of long-chain fatty acids into the mitochondrial matrix. Consequently, long-chain fatty acids are not available for p oxidation and energy production, and the production of ketone bodies (which are used by the brain) is also impaired. Regulation of intramitochondrial free CoA is also affected, with accumulation of acyl-CoA esters in the mitochondria. This in turn affects the pathways of intermediary metabolism that require CoA, for example the TCA cycle, pyruvate oxidation, amino acid metabolism, and mitochondrial and peroxisomal -oxidation. Cardiac muscle is affected by progressive cardiomyopathy (the most common form of presentation), the CNS is affected by encephalopathy caused by hypoketotic hypoglycaemia, and skeletal muscle is affected by myopathy. 

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