Fatty acids, as fuel

The reaction involves biotin as a carrier of activated HCO3 (Fig. 14-18). The reaction mechanism is shown in Figure 16-16. Pyruvate carboxylase is the first regulatory enzyme in the gluconeogenic pathway, requiring acetyl-CoA as a positive effector. (Acetyl-CoA is produced by fatty acid oxidation (Chapter 17), and its accumulation signals the availability of fatty acids as fuel.) As we shall see in Chapter 16 (see Fig. 16-15), the pyruvate carboxylase reaction can replenish intermediates in another central metabolic pathway, the citric acid cycle. 

Increases ATP production in muscle Increases availability of fatty acids as fuel... 

Tissues that cannot use fatty acids as fuel, and why... 

Answer Muscle proteins are selectively degraded by proteases in myocytes, and the resulting amino acids move, in the bloodstream, from muscle to liver. In the liver, glucogenic amino acids are the starting materials for gluconeogenesis, to provide glucose for export to the brain (which cannot use fatty acids as fuel). 

The Utilization of Fatty Acids as Fuel Requires Three Stages of Processing... 

Both muscle and liver use fatty acids as fuel when the hlood-glucose level drops. Thus, the blood-glucose level is kept at or above 80 mg/dl by three major factors (1) the mobilization of glycogen and the release of glucose by the liver, (2) the release offatty acids by adipose tissue, and (3) the shift in the fuel usedfrom glucose to fatty acids by muscle and the... 

The enzymes in the pathways of fatty acid activation and p-oxidation (the synthetases, the carnitine acyltransferases, and the dehydrogenases of p-oxidation) are somewhat specific for the length of the fatty acid carbon chain. The chain length specificity is divided into enzymes for long-chain fatty acids (C20 to approximately C12), medium-chain (approximately C12 to C4), and short-chain (C4-C2). The major lipids oxidized in the liver as fuels are the long-chain fatty acids (palmitic, stearic, and oleic acids), because these are the lipids that are synthesized in the liver, are the major lipids ingested from meat or dairy sources, and are the major form of fatty acids present in adipose tissue triacylglycerols. The liver, as well as many other tissues, uses fatty acids as fuels when the concentration of the fatty acid-albumin complex is increased in the blood. 

Fatty acids appear in the bloodstream in one of two forms as non-esterified fatty acids (NEFA) or in lipoproteins. NEFA have a very short half-life in the blood. The bulk of circulating NEFA arise from the hydrolysis of triacylglycerols stored within adipose tissue and are released into the bloodstream, where their transport is facilitated by albumin, which has multiple binding sites for fatty acids (Frayn, 2003). Plasma NEFA are destined to be used mainly as energy sources (see Section E.l on fatty acids as fuels). 

There is a continuous release of non-esterified fatty acids from adipose tissue. In the fed state most of the fatty acids are taken up by the liver, re-esterified to form triacylglycerol and exported in VLDL (section 5.6.2.2). This apparently futile (and ATP-expensive) cycling between lipolysis in adipose tissue and re-esterification in the liver permits increased utilization of fatty acids as fuel in muscle by increasing the rate of fatty acid uptake into muscle without the need to increase the rate of lipolysis. As discussed in section 10.6, the extent to which muscle utilizes fatty acids is determined to a considerable extent by the intensity of physical activity, rather than by their availability. 

The following cells can utilize fatty acids as fuels... 

HMG is an important intermediate in cholesterol biosynthesis and this pathway provides a link between fatty acid and cholesterol metabolism. Ketone bodies are also excellent fuels for the liver and even brain during starvation, even though brain cannot utilize long chain fatty acids as fuels. 

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