Betaine aldehyde, choline dehydrogenase

Betaine, formation of, 260 Betaine aldehyde, choline dehydrogenase and, 261, 262... 

The oxidation of choline to betaine is catalyzed by two enzymes. First, choline is oxidized to betaine aldehyde by an enzyme which is found in mitochondria in membrane-bound form. This enzyme is believed to be a flavoprotein containing nonheme iron. Betaine aldehyde is then oxidized to betaine by a soluble enzyme, which is NAD-linked. Betaine aldehyde dehydrogenase appears to be present both in mitochondria and the soluble fraction of liver 243, 246). 

The existence of choline dehydrogenase was first demonstrated by Mann and Quastel in 1937 247, 248) in extracts of rat liver and kidney. These authors also obtained evidence that the first oxidation product of choline was betaine aldehyde. Others showed subsequently that choline oxidase activity resided in the mitochondrial fraction of rat liver and is linked to the respiratory chain 249, 250). Detergents 251, 252), solvent treatment of fragmented mitochondria 253), and venom phospholipase 254-256) have been used for extraction and solubilization of choline dehydrogenase. Among these, the best method reported to date appears to be the digestion of acetone-powdered mitochondria with venom phospholipase. Choline dehydrogenase, partially purified from phospholipase extracts of rat liver mitochondria, contains 1 mole of flavin and 4 g-atoms of nonheme iron per 850,000 g protein. The flavin is claimed to be acid-... 

Figure 14.4. Catabolism of choline. Choline dehydrogenase, EC 1.1.99.1 betaine aldehyde dehydrogenase, EC 1.2.1.8 and homocysteine methyltransferase, EC 2.1.1.5. Relative molecular masses (Mr) choline, 104.2 betaine, 117.2 dimethylglycine, 102.2 methylglycine, 88.2 and glycine, 74.2. THF, tetrahydrofolate.

Once choline has entered the cell, its normal fate is rapid phosphorylation by choline kinase (Fig. 3). In neurons choline is also converted to the neurotransmitter, acetylcholine. Choline can also be oxidized to betaine [-00C-CH2-N (CH3)3] in the liver and kidney. In liver, betaine is an important donor of methyl groups for methionine biosynthesis. Betaine is produced in mitochondria into which choline is transported by a specific transporter on the inner membranes. Next, choline is oxidized to betaine aldehyde by choline dehydrogenase on the inner leaflet of the mitochondrial inner membranes and the subsequent conversion to betaine is catalyzed by betaine-aldehyde dehydrogenase in the mitochondrial matrix. Betaine can be transported into kidney medulla by a betaine transporter. In renal medulla and many plants and organisms, betaine accumulates as an osmolyte (a small organic solute that accumulates in response to hypertonicity without adverse effects to the cell or organism) (J.S. Handler, 1992). Hypertonicity of the renal medulla is important for the kidney s ability to concentrate urine. 

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