Short-chain fatty adds metabolism

Carnitine is required for transport of longoxidative metabolism as well as in the formation of ketone bcidies, The concentration of free carnitine in muscle is about 4,0 mmol/kg. The concentration of carnitine bound to long-chain fatty adds (fatty acyl-camitine) is lower, about 0,2 mmol/kg. Short-chain fatty adds, including acetic, are also esterified to carnitine, but the functions of these complexes are not clear. There is some indication that keto forms of BCAAs (BCKAs) can also be esterified to carnitine. These complexes can then be transported into the mitochondria for complete oxidation of the BCKAs, The importance of this mode of BCKA transport is not dear (Takakura et ai., 1997). 

Wegener, W.S., H.C. Reeves, R. Rabin, and S.J. Ajl. 1968. Alternate pathways of metabolism of short-chain fatty adds. Bacteriol. Rev. 32 1-26. 

Various pathways are employed for the degradation of branched-chain fatty acids, some of which arise from the metabolism of the branched-chain amino acids (see Leucine). Short-chain fatty adds are converted to their feitty acyl derivatives within the mitochondria, but long-chain fatty adds can be activated only by the endoplasmic reticulum and outer mi-tochondritd membrane. Long-chain acyl-CoA caimot penetrate the itmer mitochondrial membrane, and must be transported into the mitochondria as acyl-camitine (Fig. 3). 

In order to be metabolized, long-chain fatty acids must first undergo conjugation to carnitine for transport by the acylcamitine-camitine carrier across the mitochondrial inner membrane [139]. Short-chain fatty acids enter the mitochondria through monocarboxylic acid transporters [139]. Studies were carried out to assess the effects cephaloridine, cephaloglydn and cephalexin on the mitochondrial oxidative metabolism of fatty adds such as butyrate and pahnitate [67]. 

Kabir and Kimura fmther investigated the tissue distribution of C-octacosanol in liver and muscle of rats after a series of administrations. They found the highest amoimt of radioactivity in the liver (9.5% of administered dose), followed by the digestive tract (8.2% of administered dose) and the muscle (3.5% of administered dose). Interestingly enough, the radioactivity in the liver disappeared rapidly, while the muscle seemed to be able to store a considerable amount in response to the dose administered. More recently, Menendez et al. demonstrated that octacosanoic acid, as well as short-chain saturated and unsaturated fatty acids, are formed after an oral dosing of policosanol in rats and monkeys. These results reinforce the idea that octacosanol metabolism is linked to fatty add metabolism via P-oxidation. ... 

In mitochondria, there are four fatty acyl CoA dehydrogenase species, each of which has a specificity for either short-, mediurr-long-, or very-long-chain fatty acids. MCAD deficiency, an autos mal, recessive disorder, is one of the most common inborn errors of metabolism, and the most common inborn error of fatty add oxidation, being found in 1 in 12,000 births in the west, and 1 in 40,000 worldwide. It causes a decrease in fatty acid oxidation and severe hypoglycemia (because the tissues cannot obtain full ener getic benefit from fatty acids and, therefore, must now rely on glu cose). Treatment includes a carbohydrate-rich diet. [Note Infants are particularly affected by MCAD deficiency, because they rely for their nourishment on milk, which contains primarily MCADs. 

---