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an acetyl thioester

S-CoA

Figure 2.14 The final steps in the oxidation ofpyruvic acid with thiamine diphosphate and lipoic acid to give acetyl coenzyme A

2.2.5 Tetrahydrofolic Acid

The ultimate source of a one-carbon fragment is tetrahydrofolic acid, which obtains one carbon atom from formic acid, formaldehyde, or the amino-acids serine or glycine. The carbon atom from one of these sources becomes attached to N-5 of the folic acid and is reduced to methyl with the now familiar NADH (Figure 2.15).

cho ch2oh ch3

nadh nadh j^y-

Figure 2.15 The reduction of a one-carbon fragment attached to tetrahydrofolic acid to give the source of a methyl group. "C" represents one of several sources of a single carbon atom. This sequence of reactions can run in either direction, to give a methyl group from a formyl group, or to produce a formyl group from a methyl group as required

2.2.6 S-Adenosylmethionine

The methyl group attached to N-5 of tetrahydrofolic acid becomes transferred to S-adenosylhomocysteine and the S-adenosylmethionine thus formed is the compound that transfers methyl groups (for methyl esters and ethers, and N-methyl groups) in nature (Figure 2.16).

S-adenosylhomocysteine S-adenosylmethionine S-adenosylhomocysteine

Figure 2.16 Reaction between 5-methyltetrahydrofolic acid and S-adenosylhomocysteine gives S-adenosylmethionine which can react with an alcohol, phenol, or carboxylic acid to give a methyl ether, a phenolic methyl ether or a methyl ester respectively, regenerating S-adenosylhomocysteine

2.2.7 Pyridoxal Phosphate

Pyridoxal phosphate is the coenzyme that removes amine groups in metabolizing amino-acids (Figure 2.17). This is achieved by a series of reactions while the pyridoxal phosphate is bound to a transaminase

Figure 2.15 The reduction of a one-carbon fragment attached to tetrahydrofolic acid to give the source of a methyl group. "C" represents one of several sources of a single carbon atom. This sequence of reactions can run in either direction, to give a methyl group from a formyl group, or to produce a formyl group from a methyl group as required tetrahydrofolic acid tetrahydrofolic acid

n if

The overall reaction is: R C COO- + pyridoxal " R-C-COOH + pyridoxamine

NH3+

Figure 2.17 The removal of ammonia from an amino-acid by pyridoxal phosphate (PLP) and a transaminase enzyme. The PLP is held tightly to the enzyme by a lysine and ionic bonding of the phosphate group. B indicates some general base n if

The overall reaction is: R C COO- + pyridoxal " R-C-COOH + pyridoxamine

NH3+

Figure 2.17 The removal of ammonia from an amino-acid by pyridoxal phosphate (PLP) and a transaminase enzyme. The PLP is held tightly to the enzyme by a lysine and ionic bonding of the phosphate group. B indicates some general base enzyme by several interactions. Pyridoxal forms an imine with the amino-acid, and that is converted to an imine of pyridoxamine and a keto-acid. Hydrolysis of the imine gives an a-keto-acid and pyridoxamine which must be converted back to pyridoxal for re-use. In the metabolism of proteins the protein is first broken down to the individual amino-acids, which are de-aminated in this way. The carbon skeleton of the amino-acid (now as an a-keto-acid) is passed to the citric acid cycle (Figure 1.1) to be converted to energy. In fish the very toxic ammonia is usually excreted directly. In higher animals it is converted into harmless products, in insects uric acid is the important one. In mammals the amine group is transferred to the urea cycle and is excreted as urea.

Pyridoxal is also used to move amino groups between amino-acids and, with different enzymes takes part in a number of other reactions involving amino-acids. An example of the steps by which an amino-acid

Figure 2.18 The sequence of steps by which an amino-acid attached to pyridoxal and a decarboxylating enzyme is converted to an amine and C02

N CH3

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