Choline and methionine are intricately linked in cellular metabolism, specifically within the one-carbon (1C) metabolism pathway, where they function together to regulate methionine synthesis, provide methyl groups, and influence energy metabolism (glucose and fatty acid oxidation).

Methionine Synthesis and the Role of Choline
Betaine Pathway: Methionine is regenerated from homocysteine (Hcy) via a reaction catalyzed by betaine-homocysteine methyltransferase (BHMT). Betaine is a derivative of choline.

Folate Pathway: Alternatively, methionine is regenerated via 5-methyltetrahydrofolate-homocysteine methyltransferase, which uses a 1-carbon unit generated from choline.

S-adenosylmethionine (SAM): Methionine is converted to SAM, the primary methyl donor for numerous methylation reactions.

Choline Synthesis: Choline can be synthesized from methionine via S-adenosylmethionine (SAM) through the phosphatidylethanolamine N-methyltransferase (PEMT) pathway.

Choline and Carboxylic Acids (Metabolism)
Choline & Fatty Acids: Choline is essential for synthesizing phosphatidylcholine (PC), a component needed for exporting triglycerides out of the liver via very-low-density lipoproteins (VLDL).

Carboxylic Acid Oxidation: Choline supplementation can reduce reactive oxygen species (ROS) caused by fatty acid (FA) oxidation.

Pyruvate: Choline has been shown to interact with pyruvate (a carboxylic acid) metabolism, specifically reducing the export of 3-hydroxybutyrate (BHB) from hepatocytes, likely by directing fatty acids into VLDL export rather than oxidation.

Glucose Metabolism and Choline/Methionine
Glucose Regulation: Supplemental choline and methionine are used to increase glucose supply for lactogenesis in dairy cows.

Choline & Glycogen: Increased choline supply can increase cellular glycogen in hepatocytes, possibly by shifting glucose-6-phosphate away from direct glycolysis.

Methionine as a Glucogenic Amino Acid: Methionine can be converted into succinyl-CoA and enter the TCA cycle, potentially contributing to gluconeogenesis.

Interdependence: Both nutrients are often studied together (methionine-choline-deficient or MCL diets) because their deficiency disrupts lipid metabolism and causes fatty liver.

Summary of Interconnections
Choline provides methyl groups to regenerate methionine via betaine.

Methionine provides methyl groups to synthesize choline.

Choline reduces hepatic triglyceride (carboxylic acid) accumulation by driving VLDL synthesis.

Choline and Methionine both support gluconeogenesis (glucose synthesis) to manage energy, particularly during metabolic stress.

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Choline and betaine are critical methyl (CH3) donors in one-carbon metabolism, crucial for producing S-adenosylmethionine (SAM). Choline is converted in the liver to betaine, which transfers a methyl group to homocysteine, forming methionine. Betaine (trimethylglycine) contains a carboxylic acid-derived group, while choline contains a hydroxyl group.

Choline's conversion to betaine is a vital metabolic pathway, particularly when folate-dependent methylation is limited, making betaine an efficient alternative methyl source.