Solid model representations of a multimeric protein.

placed on the oxidation of choline to betaine via betaine aldehyde which is catalysed by the choline oxidase system. Recent research has indicated that this pathway may indeed be very important for the scavenging of methyl groups from choline 12 I. T h e catabolism of betaine produces one-carbon fragments ;IS ;I result of the sequential demethylation o f betaine to form glycine. T h e first step provides an active methyl group in the form of dimethylglycine and is the only alternative reaction to the folate route for the production of mcthionine from homocysteinc via betaine-homocystcine methyltransferasc 13 I. Using I H 1i.m.r. spectroscopy, we have previously observed the excretion o f relatively large amounts o f betaine (up to I mol/mol o f creatinine) in the urine of human nconatcs and young rats 141. T h e origin o f urinary betaine was further investigated by administering doses of choline chloride ( I ? g/kg body wt.) to weanling rats (age 25 days) housed in metabolic cages and by monitoring their urinary metabolite pattern using ' H n m r . analysis. T h e latter was carried out on either a Bruker WM400 or Jeol GSXSOO spectrometer using ii single pulse sequence with pulse angle 35" and a pulse recycle time o f 2 s. 'Typically 100-400 acquisitions were collected per spectrum t o provide a sufficiently high signal-to-noise ratio. T h e administration o f choline by either intraperitoneal injection or intragastric tube induced large increases in the excretion of betainc and trimethylamine-N-oxide (Fig. 1 ( I and h). Rats dosed with oral choline also excreted elevated amounts of trimethylamine and dimethylamine, probably a s via i.p. injection was excreted unchanged. To elucidate whether the increase in urinary betainc was a by-product o f microbial enzyme activity, we treated weanling rats with the broad-spectrum antibiotic neomycin sulphate for 4 days before administering a dose of oral choline (2 g/kg body wt.). A s expected, the levels of urinary trimethylamine and trimethylamine-N-oxide were substantially reduced; however, betaine output in the urine was even higher. These results suggest that the gut mucosa may be a major site o f betaine synthesis from dietary choline and that a larger proportion of the cholinc administered is oxidized to betaine under conditions where the intestinal microbial flora are significantly reduced. Acid-soluble extracts of liver and kidney tissue from newly weaned rats were also examined by ' H n.m.r. spectroscopy. Relatively large amounts of betaine were measured in the liver compared with the kidney. This accumulation of betaine in young rat liver may be a mechanism in the neonatal animal for removing excess choline from the portal circulation and simultaneously scavenging methyl groups for the consequent formation of one-carbon units and methionine.