Fasting fatty acid transport

Interconversion between ACAC and is dependent upon the NADiNADH ratio. Hydroxybutyrate dehydrogenase (HBDH) is localised mainly in the mitochondria. During fasting, fatty acids are transported to the liver to undergo beta oxidation. 

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. 

Extracellular anandamide, after it serves its function, is rapidly taken up by neuronal and non-neuronal cells by a high-affinity carrier-mediated transport mechanism. This mechanism meets key criteria of carrier-mediated transport, such as fast rate (t, of approximately 4 min), temperature dependence, satura-bility, and substrate selectivity (Beltramo et ah, 1997 Hillard et al., 1997). Furthermore, the transportation of anandamide is independent of sodium ions and is not affected by metabolic inhibitors. The second endogenous camiabinoid, 2-AG, competes for uptake with anandamide. It has been variously reported to exhibit a 2-fold higher affinity for the anandamide transporter than anandamide (Jarrahian et al, 2000), or equal affinity (Piomelli et al, 1999). The molecular structure of this hypothetical anandamide transporter remains unknown. However, it is selective for fatty acid amides or esters, and it is not a fatty acid transporter (Piomelli et al, 1999 Jarrahian et al, 2000). Very recent results indicate that anandamide uptake is a process driven by metabolism and other downstream events, rather than by a specific membrane-associated anandamide carrier (Glaser et al, 2003). 

The regulation of fat metabolism is relatively simple. During fasting, the rising glucagon levels inactivate fatty acid synthesis at the level of acetyl-CoA carboxylase and induce the lipolysis of triglycerides in the adipose tissue by stimulation of a hormone-sensitive lipase. This hormone-sensitive lipase is activated by glucagon and epinephrine (via a cAMP mechanism). This releases fatty acids into the blood. These are transported to the various tissues, where they are used. 

Carnitine is a vitamin-like quaternary ammonium salt, playing an important role in the human energy metabolism by facilitating the transport of long-chained fatty acids across the mitochondrial membranes. An easy, fast, and convenient procedure for the separation of the enantiomers of carnitine and 0-acylcarnitines has been reported on a lab-made teicoplanin-containing CSP [61]. The enantioresolution of carnitine and acetyl carnitine was enhanced when tested on a TAG CSP, prepared in an identical way [45]. Higher a values were reached also in the case of A-40,926 CSP [41]. 

As the fast progresses, more of the adipose-derived fatty acids are transported in the bloodstream as complexes with albumin and taken up by the liver. 

Individuals with either type of diabetes are unable to take up glucose efficiently from the blood recall that insulin triggers the movement of GLUT4 glucose transporters to the plasma membrane of muscle and adipose tissue (see Fig. 12-8). Another characteristic metabolic change in diabetes is excessive but incomplete oxidation of fatty acids in the liver. The acetyl-CoA produced by JS oxidation cannot be completely oxidized by the citric acid cycle, because the high [NADH]/[NAD+] ratio produced by JS oxidation inhibits the cycle (recall that three steps convert NAD+ to NADH). Accumulation of acetyl-CoA leads to overproduction of the ketone bodies acetoacetate and /3-hydroxybutyrate, which cannot be used by extrahepatic tissues as fast as they are made in the liver. In addition to /3-hydroxybutyrate and acetoacetate, the blood of diabetics also contains acetone, which results from the spontaneous decarboxylation of acetoacetate ... 

Liquid fuels play a key role in modem lifestyles. Their liquid nature offers convenience in being transportable and easy to use. Diesel, spark-ignition and Jet engines are the result of this convenience. Unfortunately, the hydrocarbons, which play the major role as liquid fuel are finite, and upon combustion contribute to the accumulation of carbon dioxide in the atmosphere. It is not surprising that alternate renewable liquid fuels are receiving attention. These include ethanol, methanol, fatty acid methyl esters and fast pyrolysis oils. All can be produced from renewable resources. Ethanol may be formed by fermentation of sugars and thereby indirectly from cellulose and starches. Methanol can be produced from carbon monoxide and... 

One molecule of oxygen accepts two pairs of electrons, one from palmitoyl-CoA and the other from NADPH or NADH. The electrons NAD(P)H are transported via cytochrome-bs reductase to cytochrome bs (microsomal electron transport Chapter 14). An enzyme-bound superoxide radical is responsible for the oxidation of acyl-CoA. Four desaturases specific for introducing cis double bonds at C9, Ca, C5, and C4, respectively, are known. If the substrate is saturated, the first double bond introduced is C9. With an unsaturated substrate, other double bonds are introduced between the carboxyl group and the double bond nearest the carboxyl group. Desaturation yields a divinylmethane arrangement of double bonds (—CH=CH—CH2—CH=CH—). Usually desaturation alternates with chain elongation. Desaturation is inhibited by fasting and diabetes. The oxidation of unsaturated fatty acids occurs in mitochondria. 

Fatty acids released from adipose tissue are the source of ketone bodies (Figure 22-22). Fasting, high levels of glucagon and catecholamine, and a low level of insulin result in rapid lipolysis and ready availability of fatty acids. Fatty acids, after being converted to CoA thioesters, are oxidized in the mitochondria. The rate-limiting step in the oxidation process is the transport of fatty acyl-CoA... 

The liver also plays a central role in lipid metabolism. When excess fuel is available, the liver synthesizes fatty acids. These are used to produce triglycerides that are transported from the liver to adipose tissues by very low density lipoprotein (VLDL) complexes. In fact, VLDL complexes provide adipose tissue with its major source of fatty acids. This transport is particularly active when more calories are eaten than are burned During fasting or starvation conditions, however, the liver converts fatty acids to acetoacetate and other ketone bodies. The liver cannot use these ketone bodies because it lacks an enzyme for the conversion of acetoacetate to acetyl CoA. Therefore the ketone bodies produced by the liver are exported to other organs where they are oxidized to make ATP. 

---