Anabolic pathway

Anabolic Pathways Diverge, Synthesizing an Astounding Variety of Biomolecules from a Limited Set of Building Blocks... 

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. 

Gluconeogencsis (Section 29.8) The anabolic pathway by which organisms make glucose from simple precursors. 

The L-threonine (EC 4.1.2.5), D-threonine (EC 4.1.2.-) or L-allothreonine aldolases (EC 4.1.2.6 synonymous to S1IMT) can be used for resolution of racemic (allo)threonine mixtures by highly selective cleavage of the unwanted isomers42, but can also efficiently direct the anabolic pathways. The substrate spectrum includes propanal, butanal and dodecanal43. 

Figure 6.1 Scheme for catabolic and anabolic pathways (shown is their interrelation through ATP-ADP system and amphibolic metabolite cycle)... 

During catabolic and anabolic processes, a renovation of the molecular cellular components takes place. It should be emphasized that the catabolic and anabolic pathways are independent of each other. Be these pathways coincident and differing in the cycle direction only, the metabolism would have been side-tracked to the so-called useless, or futile, cycles. Such cycles arise in pathology, where a useless turnover of metabolites may occur. To avoid this undesirable contingency, the synthetic and degradative routes in the cell are most commonly separated in space. For example, the oxidation of fatty acids occurs in the mitochondria, while the synthesis thereof proceeds extramitochondrially, in the microsomes. 

Carbohydrate metabolism in the organism tissues encompasses enzymic processes leading either to the breakdown of carbohydrates (catabolic pathways), or to the synthesis thereof (anabolic pathways). Carbohydrate breakdown leads to energy release or intermediary products that are necessary for other biochemical processes. The carbohydrate synthesis serves for replenishment of polysaccharide reserve or for renewal of structural carbohydrates. The effectiveness of various routes of carbohydrate metabolism in tissues and organs is defined by the availability of appropriate enzymes in them. 

We will return to an overview of anabolic pathways shortly, but first we want to examine in more detail the two important catabolic pathways, glycolysis and the tricarboxylic acid cycle. 

Allosteric regulatory molecules are small molecular weight compounds which may be coenzymes (NAD+, ATP, etc.) or intermediate substrates, possibly generated by enzymes found within the same pathway as the regulated enzyme. Alternatively, the allosteric modulator may be generated within another, perhaps complementary, pathway. For example, a regulator may be stimulatory for a catabolic route and at the same time inhibitory for the opposing anabolic pathway. 

Distinct coenzymes are required in biological systems because both catabolic and anabolic pathways may exist within a single compartment of a cell. The nicotinamide coenzymes catalyze direct hydride transfer (from NAD(P)H or to NAD(P)+) to or from a substrate or other cofactors active in oxidation-reduction pathways, thus acting as two-electron carriers. Chemical models have provided... 

Anabolic metabolic pathways are the flip side of catabolic ones. Anabolic reactions are biosynthetic that is, they create complex molecules out of simpler ones. Anabolic pathways are reductive in nature and consume energy. In all these ways, anabolic pathways stand in contrast to catabolic ones. It is frequently the case that the end product of an anabolic pathway will inhibit the first enzyme in the same pathway. This makes a good deal of sense. Anabolic pathways require energy and if there is enough end product available there is little reason to keep making more of it. So an excess of the end product simply turns off the pathway by inhibiting the first enzyme ... 

While NADH exclusively supplies oxidative phosphorylation, NADPH+H" —a very similar coenzyme—is the reducing agent for anabolic pathways. NADPH + is mainly formed in the pentose phosphate pathway (PPP, 1 see p. 152). 

The tricarboxylic acid cycle also supplies important precursors for anabolic pathways. 

The intermediates of the tricarboxylic acid cycle are present in the mitochondria only in very small quantities. After the oxidation of acetyl-CoA to CO2, they are constantly regenerated, and their concentrations therefore remain constant, averaged over time. Anabolic pathways, which remove intermediates of the cycle (e.g., gluconeogenesis) would quickly use up the small quantities present in the mitochondria if metabolites did not reenter the cycle at other sites to replace the compounds consumed. Processes that replenish the cycle in this way are called anaplerotic reactions. 

I—lA Catabolic pathway I Anabolic pathway I % Anaplerotic reaction... 

The pentose phosphate pathway (PPP, also known as the hexose monophosphate pathway) is an oxidative metabolic pathway located in the cytoplasm, which, like glycolysis, starts from glucose 6-phosphate. It supplies two important precursors for anabolic pathways NADPH+H+, which is required for the biosynthesis of fatty acids and isopren-oids, for example (see p. 168), and ribose 5-phosphate, a precursor in nucleotide biosynthesis (see p. 188). 

Anabolic pathways are frequently stimulated under conditions of abundance (ie, high levels of cellular energy and availability of precursor molecules for the pathway) and inhibited when energy and precursors are low. 

The aroma of intact black currant fruit is mostly produced by anabolic pathways of the plant, and production of fruit volatiles occurs mainly during a short ripening period [112]. The aroma profile of black currant shares similarities with that of other berry fruits, although terpenes are more abundantly present in black currant [107]. Black currant is mainly used for the production of juice. Over 150 volatile compounds have been reported from either black currant berries and/or juice, of which the major groups are monoterpenes, sesquiterpenes, esters and alcohols [107]. Processing of berries to juice has been shown to lead to major changes in the aroma composition [113-118]. 

The bioavailability of azathioprine (80%) is superior to 6-MP (50%). After absorption azathioprine is rapidly converted by a nonenzymatic process to 6-MP. 6-Mercaptopurine subsequently undergoes a complex biotransformation via competing catabolic enzymes (xanthine oxidase and thiopurine methyltransferase) that produce inactive metabolites and anabolic pathways that produce active thioguanine nucleotides. Azathioprine and 6-MP have a serum half-life of less than 2 hours however, the... 

FIGURE 3 Energy relationships between catabolic and anabolic pathways Catabolic pathways deliver chemical energy in the form of ATP, NADH, NADPH, and FADH2. These energy carriers are used in anabolic pathways to convert small precursor moleculesinto cell macromolecules. 

Chapters 20 through 22 describe the major anabolic pathways by which cells use the energy in ATP to produce carbohydrates, lipids, amino acids, and nucleotides from simpler precursors. In Chapter 23 we step back from our detailed look at the metabolic pathways—as they occur in all organisms, from Escherichia coli to humans—and consider how they are regulated and integrated in mammals by hormonal mechanisms. 

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