Many coenzymes (see pp. 104ff.) serve to activate molecules or groups that are poorly reactive. Activation consists of the formation of reactive intermediate compounds in which the group concerned is located at a higher chemical potential and can therefore be transferred to other molecules in an exer-gonic reaction (see p. 124). Acetyl-CoA is an example of this type of compound (see p. 12).
ATP and the other nucleoside triphosphate coenzymes not only transfer phosphate residues, but also provide the nucleotide components for this type of activation reaction. On this page, we discuss metabolites or groups that are activated in the metabolism by bonding with nucleosides or nucleotides. Intermediates of this type are mainly found in the metabolism of complex carbohydrates and lipids.
A. Activated metabolites 3
1. Uridine diphosphate glucose (UDPglucose)
The inclusion of glucose residues into polymers such as glycogen or starches is an ender-gonic process. The activation of the glucose building blocks that is required for this takes places in several steps, in which two ATPs are used per glucose. After the phosphorylation of free glucose, glucose 6-phosphate is isomer-ized to glucose 1-phosphate (a), reaction with UTP (b) then gives rise to UDPglucose, in which the anomeric OH group at C-1 of the sugar is bound with phosphate. This "energy-rich" compound (an acetal phosphate) allows exergonic transfer of glucose residues to glycogen (c; see pp. 156,408) or other acceptors.
2. Cytidine diphosphate choline (CDPcholine)
The amino alcohol choline is activated for inclusion in phospholipids following a similar principle (see p. 170). Choline is first phos-phorylated by ATP to form choline phosphate (a), which by reaction with CTP and cleavage of diphosphate, then becomes CDPcholine. In contrast to (1), it is not choline that is transferred from CDPcholine, but rather choline phosphate, which with diacylglycerol yields phosphatidylcholine (lecithin).
3. Phosphoadenosine phosphosulfate (PAPS)
Sulfate residues occur as strongly polar groups in various biomolecules—e.g., in gly-cosaminoglycans (see p. 346) and conjugates of steroid hormones and xenobiotics (see p. 316). In the synthesis of the "activated sulfate" PAPS, ATP first reacts with anorganic sulfate to form adenosine phosphosulfate (APS, a). This intermediate already contains the "energy-rich" mixed anhydride bond between phosphoric acid and sulfuric acid. In the second step, the 3'-OH group of APS is phosphorylated, with ATP being used again. After transfer of the sulfate residue to OH groups (c), adenosine-3',5'-bisphosphate remains.
4. S-adenosyl methionine (SAM)
The coenzyme tetrahydrofolate (THF) is the main agent by which C1 fragments are transferred in the metabolism. THF can bind this type of group in various oxidation states and pass it on (see p. 108). In addition, there is "activated methyl," in the form of S-adenosyl methionine (SAM). SAM is involved in many methylation reactions—e. g., in creatine synthesis (see p. 336), the conversion of norepi-nephrine into epinephrine (see p. 352), the inactivation of norepinephrine by methyla-tion of a phenolic OH group (see p. 316), and in the formation of the active form of the cytostatic drug 6-mercaptopurine (see p. 402).
SAM is derived from degradation of the proteinogenic amino acid methionine, to which the adenosyl residue of an ATP molecule is transferred. After release of the activated methyl group, S-adenosyl homocys-teine (SAH) is left over. This can be converted back into methionine in two further steps. Firstly, cleavage of the adenosine residue gives rise to the non-proteinogenic amino acid homocysteine, to which a methyl group is transferred once again with the help of N5-methyl-THF (see p. 418). Alternatively, homocysteine can also be broken down into pro-pionyl-CoA.
I— A. Activated metabolites b
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