Catabolism oxidative pathway

Look al the catabolism of my fistic acid shown in Figure 29.4 to see the overall results of the /3-oxidation pathway. The first passage converts the 14-carbon myristoyl CoA into the 12-carbon lauroyl CoA plus acetyl CoA, the second passage converts lauroyl CoA into the 10-carbon caproyl CoA plus acetyl CoA, the third passage converts caproyl CoA into the 8-carbon capryloyl CoA, and so on. Note that the final passage produces two molecules of acetyl CoA because the precursor has four carbons. 

Figure 29.4 Catabolism of the 14-carbon myristicacid by the 0-oxidation pathway yields seven molecules of acetyl CoA after six passages.

As a rule, the anabolic pathway by which a substance is made is not the reverse of the catabolic pathway by which the same substance is degraded. The two paths must differ in some respects for both to be energetically favorable. Thus, the y3-oxidation pathway for converting fatty acids into acetyl CoA and the biosynthesis of fatty acids from acetyl CoA are related but are not exact opposites. Differences include the identity of the acvl-group carrier, the stereochemistry of the / -hydroxyacyl reaction intermediate, and the identity of the redox coenzyme. FAD is used to introduce a double bond in jS-oxidalion, while NADPH is used to reduce the double bond in fatty-acid biosynthesis. 

CoA (see Table 17-1). A similar calculation can be made for the ATP yield from oxidation of each of the amino acids (Chapter 18). Aerobic oxidative pathways that result in electron transfer to 02 accompanied by oxidative phosphorylation therefore account for the vast majority of the ATP produced in catabolism, so the regulation of ATP production by oxidative phosphorylation to match the cell s fluctuating needs for ATP is absolutely essential. 

In the ruminant mammary tissue, it appears that acetate and /3-hydroxybutyrate contribute almost equally as primers for fatty acid synthesis (Palmquist et al. 1969 Smith and McCarthy 1969 Luick and Kameoka 1966). In nonruminant mammary tissue there is a preference for butyryl-CoA over acetyl-CoA as a primer. This preference increases with the length of the fatty acid being synthesized (Lin and Kumar 1972 Smith and Abraham 1971). The primary source of carbons for elongation is malonyl-CoA synthesized from acetate. The acetate is derived from blood acetate or from catabolism of glucose and is activated to acetyl-CoA by the action of acetyl-CoA synthetase and then converted to malonyl-CoA via the action of acetyl-CoA carboxylase (Moore and Christie, 1978). Acetyl-CoA carboxylase requires biotin to function. While this pathway is the primary source of carbons for synthesis of fatty acids, there also appears to be a nonbiotin pathway for synthesis of fatty acids C4, C6, and C8 in ruminant mammary-tissue (Kumar et al. 1965 McCarthy and Smith 1972). This nonmalonyl pathway for short chain fatty acid synthesis may be a reversal of the /3-oxidation pathway (Lin and Kumar 1972). 

A natural question is "Why has this complex pathway evolved to do something that could have been done much more directly " One possibility is that the presence of too much malonyl-CoA, the product of the P oxidation pathway of propionate metabolism (Fig. 17-3, pathways a and c), would interfere with lipid metabolism. Malonyl-CoA is formed in the cytosol during fatty acid biosynthesis and retards mitochondrial P oxidation by inhibiting carnitine palmitoyltransferase i.46 70a 75 However, a relationship to mitochondrial propionate catabolism is not clear. 

Somewhat surprisingly, within the mitochondria the ratio [NAD+]/[NADH] is 100 times lower than in the cytoplasm. Even though mitochondria are the site of oxidation of NADH to NAD+, the intense catabolic activity occurring in the (3 oxidation pathway and the citric acid cycle ensure extremely rapid production of NADH. Furthermore, the reduction state of NAD is apparently buffered by the low potential of the (3-hydroxybutyrate-acetoacetate couple (Chapter 18, Section C,2). Mitochondrial pyridine nucleotides also appear to be at equilibrium with glutamate dehydrogenase.169... 

Catabolism involves pathways composed of enzymes and chemical intermediates that are involved primarily in the breakdown of large molecules into small molecules, often by oxidation processes. Anabolism is the collection of the enzymes and chemical intermediates involved in the biological synthesis of larger molecules from smaller molecules. Anabolism often involves reduction processes. 

Know pathways of triglyceride biosynthesis and catabolism, the /3-oxidative pathway, and pathways for the degradation of pro-pionyl-CoA, branched fatty acids, and unsaturated fatty acids identify cofactors required calculate ATP yields for fatty acid oxidation know the identity of key enzymes in each pathway. 

Fatty acids are utilized as fuels by most tissues, although the brain, red and white blood cells, the retina, and adrenal medulla are important exceptions. Catabolism of fatty acids requires extramitochondrial activation, transport into mitochondria, and then oxidation via the /3-oxidative pathway. The initial step is catalyzed by fatty acyl-CoA synthetase (also called thiokinase and fatty acyl-CoA ligase), as shown in Equation (19.5). The product, fatty acyl-CoA, then exchanges the CoA for carnitine, as shown in Equation (19.6) ... 

The catabolic oxidation of glucose, to provide cellular energy, occurs principally through three linked catabolic pathways ... 

Apart from the relatively small amounts that are required for synthesis of the neurotransmitter serotonin (5-hydroxytryptamine), and for net new protein synthesis, essentially the whole of the dietary intake of tryptophan is metabolized by way of the oxidative pathway shown in Figures 8.4 and 9.4, which provides both a mechanism for total catabolism by way of acetyl coenzyme A and a pathway for synthesis of the nicotinamide nucleotide coenzymes (Section 8.3). 

How many molecules of acetyl CoA are produced by catabolism of the following laity acids, and how many passages of the /3-oxidation pathway are needed ... 

In catabolic reactions complex substances are broken down to simpler compounds with a concomitant release of free energy. The released free energy during these catabolic reactions is conserved in the form of ATP or NADPH. The major nutrients such as carbohydrates, lipids and proteins are converted to common intermediate and further metabolised in a central oxidative pathway. 

The fatty acid oxidation pathway comprises a sequence of steps frequently encountered in biology (1) oxidation of an alkane to produce an alkene (2) hydration of the alkene to form a hydrojcyl group and (3) oxidation of the hydroxyl group to form a kelo group. This three-step sequence is also found in the Krebs cycle and the isoJeucine catabolic pathway. 

As a nile, the anabolic pathway by which an organism makes a substance is not the reverse of the catabolic pathway by which the organism degrades the same substance. For exampie, the /S-oxidation pathway foi fatty acid degradation (Figure 29.2) and the cycle for fatty acid synthesis (Figure 29.8) are dearly related, but one is not the exact reverse of the other. Fatty acid synthesis involves carboxylation and decarboxylation reactions, for example, but jS-oxidation does not. 

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