Blood fatty acid concentration

The rate of ketogenesis increases in proportion to the blood fatty acid concentration. It increases during fasting and especially in uncontrolled type 1 diabetes (diabetic ketoacidosis (DKA)). 

Figure 7.14 Regulation of rate of fatty acid oxidation in tissues. Arrows indicate direction of change (i) Changes in the concentrations of various hormones control the activity of hormone-sensitive lipase in adipose tissue (see Figure 7.10). (ii) Changes in the blood level of fatty acid govern the uptake and oxidation of fatty acid, (iii) The activity of the enzyme CPT-I is controlled by changes in the intracellular level of malonyl-CoA, the formation of which is controlled by the hormones insulin and glucagon. Insulin increases malonyl-CoA concentration, glucagon decrease it. Three factors are important TAG-lipase, plasma fatty acid concentration and the intracellular malonyl-CoA concentration.

It can be considered that the saturated long chain fatty acid concentration in blood can act as a messenger for its oxidation. An increase in concentration increases rate of oxidation. 

Because insulin normally inhibits lipolysis, a diabetic has an extensive lipolytic activity in the adipose tissue. As is seen in Table 21.4, plasma fatty acid concentrations become remarkably high. /3-Oxidation activity in the liver increases because of a low insulin/glucagon ratio, acetyl-CoA carboxylase is relatively inactive and acyl-CoA-camitine acyltransferase is derepressed. /3-Oxidation produces acetyl-CoA which in turn generates ketone bodies. Ketosis is perhaps the most prominent feature of diabetes mellitus. Table 21.5 compares ketone body production and utilization in fasting and in diabetic individuals. It may be seen that, whereas in the fasting state ketone body production is roughly equal to excretion plus utilization, in diabetes this is not so. Ketone bodies therefore accumulate in diabetic blood. 

There is debate over the association between caffeine intake and cardiovascular disease. Increases in mean blood pressure, blood glucose and free fatty acid concentrations, and urinary catecholamine excretion have been... 

Susheela, A. K., Free fatty acid concentrations in normal and diseased human muscle and in blood sera from patients with neuromuscular disease. Clin. Chim. Acta 22, 219-222 (1968). 

It is unlikely that PUFAs do not reach the brain, because they can pass the blood-brain barrier rapidly. Thus, it seems more likely that they are quickly stored somewhere, so that the free concentration in the extracellular space remains too low, at least initially, to interact with ion channels. From these stores, they can be released more slowly, accounting for a delayed effect. One possibility is that they are incorporated in neuronal membranes and later liberated by activity-dependent lipase (Dumuis, Sebben, Haynes, Pin Bockaert, 1988). Alternatively, astroglial cells may buffer the rapid rise in fatty acid concentration and later release them at a much slower rate to the immediate vicinity of the neurons. 

Caffeine is also of great use for people on the anabolic diet. It has lipolytic, fat-burning properties that result in an increase in free fatty acid concentration in blood BUT ONLY ON THE HIGH FAT DIET. A high carbohydrate diet negates the fat-burning effects of caffeine (ref.7). 

After several days of starvation, the rate of fatty acid release from adipose tissue reaches its maximum. Tissues such as muscle and liver oxidize fatty acids and produce ATP, but its rate of production may not change or it can become lower as a consequence of increased efficiency in starvation. Therefore the fatty acid concentration in the blood rises as the rate of release of fatty acids from adipose tissue exceeds that of tissue usage. In contrast to other tissues, the hver continues to perform (3-oxidation even if the resulting acetyl-CoA is not consumed by the Krebs cycle. It is this feature of its metabolism that gives rise to the production of ketone bodies which serve as an alternative fuel for the brain and other tissues. 

How does a rise in fatty acid concentration in the blood lead to the stimulation of fatty acid oxidation in skeletal myocytes ... 

Determination of Volatile Fatty Acid Concentrations in Blood and Their Chromatographic Analysis... 

Free Fatty Acid Concentration and Composition in Arterial Blood Am. J. Physiol. 203 306-310 (1962) ... 

The decrease of free fatty acid concentration after administration of ketone bodies is accompanied by a fall in the concentrations of glucose and glycerol in the blood (Balasse and Ooms, 1968). Further work is required before the relative importance of the modification of the supply of metabolic fuels by ketone bodies can be correctly assessed. 

All the factors which increase free fatty acid concentrations in blood in vivo have also been shown to increase the release of the acid from the tissue into an albumin medium in vitro. These factors therefore, must exert their regulatory effect by direct action on adipose tissue. 

Animal cells can modify arachidonic acid and other polyunsaturated fatty acids, in processes often involving cyclization and oxygenation, to produce so-called local hormones that (1) exert their effects at very low concentrations and (2) usually act near their sites of synthesis. These substances include the prostaglandins (PG) (Figure 25.27) as well as thromboxanes (Tx), leukotrienes, and other hydroxyeicosanoic acids. Thromboxanes, discovered in blood platelets (thrombocytes), are cyclic ethers (TxBg is actually a hemiacetal see Figure 25.27) with a hydroxyl group at C-15. 

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