Introduction
Betaine, also known as glycine betaine and N,N,N trimethyl glycine, is
an osmolyte found across animals, plants, and microorganisms. It is a
zwitterionic amino acid derivative that can be endogenously produced by
the oxidation of choline[1 ],
and exogenously absorbed as a dietary nutrient. The name betaine comes
from its discovery from beta vulgaris (beets) in the 1860s, but
later it was found at high concentration in other dietary sources like
wheat bran, spinach, and
seafood[2-4 ]. In mammals, from
the physiological point of view, betaine serves primarily two roles: as
one of the major osmolytes accumulated in the tissues for cell volume
regulation, mainly in kidney, and as a methyl donor for the toxic
metabolite, homocysteine (Hcy), to convert it into methionine
[1 ,4 ].
The daily betaine uptake in human diet ranges from 1-2.5g/day, based on
individual consumption. The study on red blood cell physiology at high
betaine doses showed mild perturbance and suggested safe daily betaine
intake was 9-15g/day [2 ]. The
active absorption of betaine across the enterocytes is thought to be via
sodium/chloride dependent amino acid transport system (SLC36A1,
SLC36A2), and also passive sodium independent
[1 ,2 ,5 ,6 ].
A rapid adsorption and distribution up to 1-3mM within 1-2h of intake
was recorded in human studies on betaine supplementation
[2 ,7 ].
However, the tissue concentration for an osmolyte, as expected, is
higher than plasma concentration
[8 ]. Apart from diet and
supplementation, betaine can be synthesized via a two-step irreversible
process using choline in mitochondria (see figure 1). Firstly, the
enzyme choline dehydrogenase oxidates choline into betaine aldehyde. And
then, betaine aldehyde is converted to betaine by the same enzyme in the
presence of nicotinamide adenine dinucleotide (NAD+).
This betaine is catabolized via transmethylation reactions involved in
vital biological processes [2 ].
This transmethylation is catalysed by betaine-homocysteine
methyltransferase (BHMT), which detoxifies Hcy by converting it into
methionine and producing S-adenosylmethionine (SAM).