25.6 the Key Intermediote-Acetyl

Home , Carbohydrate metabolism, Citric acid cycle, Fatty acid metabolism, Lipid metabolism

25.6 The Key Intermediate-AcetylCoA 77t

tributes to energy production by entering glycolysis as dihydroxyacetone phosphate.

25.6 Thekey intermediote-acetylCoA AIMS: Toname the shoredintermediote of both carbohydrote ond fotty ocid metobolism,To list four fotes of ocetylCoA in the liver.

Now that we have seen how the body oxidizes fatty acids, we can form an Focus overall picture of the various parts of fatty acid metabolism. We can exam- Fatty acid metabolism and ine the relationships between carbohydrate metabolism and fatty acid carbohydrate metabolism metabolism at the same time. Since the liver conducts more carbohydrate intersect at acetyl CoA. metabolism and fatty acid metabolism than any other organ, this discus- sion will focus on it. Figure 25.4 showsthe relationships we will be examining in the remainder of this chapter. Refer to it often as you read on. The figure shows that

Figure25.4 Themajor pathways of lipidmetab- olismin the liverand their relation- shipto carbohydratemetabolism. 774 CHAPTER25 Lipid Metabolism

fatty acids entering the liver from the blood may be reslmthesizedinto triglycerides and stored in the adipose tissue there. Alternatively, fatty acids may be broken do',nmto aceryl CoA. Glucose is also broken do',nmto acetyl CoA. If you are beginning to suspect that aceryl CoA must be a key compound in the metabolic interplay between carbohydrate and fatty acid metabolism, you are certainly correct. Four possible fates await the acetyl CoA produced from fatty acids or glucose in the liver: 1. The acetyl CoA in the mitochondria may be oxidized to carbon dioxide and water in the citric acid cycle and respiration. This pathway, which is used if the liver cells need to generateenergy through respiration, makes it clear that the citric acid cycle is shared by both glucose metabolism and fatty acid metabolism. 2. The acetyl CoA in mitochondria may be used to synthesizethe sub- stancescalled ketonebodies.Some ketone bodies are oxidized for energy production by the liver. The remainder are transpofted to other tissues that can use them for energyproduction. Extensiveproduction of ketone bodies from acetyl CoA occurs only when no glucose is available, as in starvation or diabetes. When no glucose is available to starving brain cells, for example, they adapt to the use of ketone bodies as an energy sourcein about 48 hours. 3. The cltoplasmic acetyl CoA may be used to resynthesizefatty acids. Since some of the acetyl CoA may have come from glucose,this means that carbohydrates may be converted to fatty acids. 4. The acetyl CoA may be used to slnthesize cholesterol in the cellular cytoplasm. As with other synthetic processes,the slnthesis of fatty acids and cholesterol occurs when the body is well supplied with energy. Cells other than liver cells can carry out most of these four functions. However, only the liver adds significant quantities of ketone bodies to the bloodstreamfor transport to other tissues.

PRACTICEEXERCISE 25.5 \Mhat is the fate of acetyl CoA when the body needs energy?\Mhat is its fate when energy needs are met?

25.7Fatty ocid synthesis AIM: To exploin the odvontogesof lipid energystoroge over corbohydrateenergy storage. .1i ;! \- Carbohydratescan be convertedto fats.The key.";$;;"i,hat links@. bohydrate metabolism to fatty acid synthesisis acetyl CoA.lVhen body cells Converting carbohydrates to have more glucose than they require to meet their energy needs, they can fatty acids is an efficient way to divert some of the acetyl CoA produced by glucose catabolism to the syn- store energy. thesis offatty acids. Fatty acid synthesis and fatty acid oxidation are not the reverse of one another, though both processesdo occur in cycles.In fatty acid slmthesis,a 25.7 Fatty Acid Synthesis 775

two-carbon fragment is added to the growing fatty acid chain in each turn of the cycle rather than being removed, as it is in fatty acid oxidation. More- over, the synthesis and degradation of fatty acids involve different sets of en4lmes. The cellular locations of the two processesare different as well: Fatty acid synthesis occurs in the cytoplasm; fatty acid oxidation takes place in the mitochondria. Like most slnthetic or anabolic pathways, the slmthesis of fatty acids requires the expenditure of cellular reducing power and ATP This requirement is clearly shorrrmby the overall equation for the slnthesis of palmitic acid. o o 8CH3C-S-CoA + TATP + 14NADH ------CHS-eCHTJFC-OH + TADP + 14NAD+ + 8CoA + 6H2O + 7R Acetyl CoA Palmitic acid

The newly synthesized fatty acids are incorporated into triglycerides and are stored as depot fat in adipose tissues. The amount of energy that is re- Lipids are a concentrated storageform of energy compared with carbo- leasedupon complete oxidation of hydrates. There are two reasons for this. First, fatty acids are in a more a fuel can be measuredinabomb reduced state than carbohydrates;the carbon chains offatty acids are gen- calorimeter. Aweighed sample of a erally saturated hydrocarbons, whereasthe carbon chains of most carbohy- fuel is burned in a closedchamber drates are already partially oxidized to alcohols. Thus the bonds of fatty situated in a water-filled, insulated acidshave more energyto releaseupon completeoxidation to carbon diox- container. The heat given off is ide and water than the calculated from the measured bonds of carbohydrates.This is why I g of fat increasein the temperature of the releases9 kcal of energy but I g of carbohydrate releasesonly 4 kcal. Sec- knor,rmmass of water. ond, fats are stored in a nearly anhydrous, or dry state. In contrast, for each gram of carbohydrate stored as glycogen,nearly 2 g of water is carried along. A reasonableamount of body fat is necessaryand beneficial, but main- taining proper body weight is a problem for many people. From the metabolic point of view dieting consists of reducing caloric intake so that stored fats must be degraded to meet energy needs. Some people try to reduce by eliminating all fatty foods from their diets. By eliminating foods that con- tain fats, however, one runs the risk of also eliminating essential vitamins and minerals contained in these foods. Moreover,if the decreasedfat intake is more than compensatedby an increasedintake of carbohydrates-in starchy foods, sweets, soda, and so forth-a person not only fails to lose weight but actually gains. Human beings convert carbohydratesto fats, but people do not convert fats to carbohydrates. Human cells have no en4lrne that can catalyze the conversion of acetyl CoA to pyruvate, a compound required for gluconeo- genesis.Some bacteria, however,do have such an enzymq they convert fats to carbohydrates as part of their normal metabolism.

PRACTICEEXERCISE 25-4 A personhas a basalmetabolism of 1800Calories per day.Calculate (a) the weight of fat that must be oxidized to CO2and H2O to provide this amount of energy and (b) the weight of glucose that must be metabo- lized to releasethis amount of energy.