Methionine

Powers methylation

Methionine is an essential amino acid. It's the first amino acid of every protein the body makes, and its sulfur-linked methyl group (–S–CH₃) makes it the source of the body's main methyl donor. The enzyme MAT attaches ATP to methionine to form S-adenosylmethionine (SAM), and the positive charge on its sulfur makes the methyl group easy to hand off. More than 200 methyltransferase enzymes take that methyl group and put it on something else, leaving S-adenosylhomocysteine (SAH) behind.¹

SAM's methyl groups go into:

• Creatine, made in the liver from guanidinoacetate. Together with phosphatidylcholine, it uses the largest share of the body's methyl groups. Eating creatine from meat spares that methyl demand.²
• Phosphatidylcholine, made in the liver by adding three methyls to phosphatidylethanolamine. The liver needs it to package fat into VLDL. That's why low methyl supply leads to fatty liver.
• DNA and histones: the epigenetic tags that keep genes silenced.
• Neurotransmitters and hormones: adrenaline, melatonin, and inactivating dopamine and oestrogens (through COMT).

SAH blocks most methyltransferases, so it has to be cleared, and it's broken down into homocysteine. The SAM:SAH ratio is the cell's "methylation capacity," and it falls when homocysteine can't be cleared.¹ Recycling homocysteine back to methionine needs folate and B12, or betaine (from choline) in the liver.

Feeds glutathione

Homocysteine sits at a fork. It can be recycled back to methionine, or sent one way down the transsulfuration pathway to make cysteine:¹

1. Cystathionine β-synthase (needs B6) joins homocysteine to serine, making cystathionine.
2. Cystathionine γ-lyase (also B6) splits cystathionine into cysteine and α-ketobutyrate.

Cysteine is the limiting building block for glutathione, and it also goes into taurine and sulfate. SAM itself steers the fork. When SAM is high, it switches on cystathionine β-synthase and switches off the recycling enzyme MTHFR. So surplus methionine flows to cysteine and glutathione, and a shortage is held back for methylation. In the liver, about half of glutathione's cysteine comes from methionine this way.¹

Needs glycine to stay balanced

The liver has a built-in overflow valve for excess methionine: glycine N-methyltransferase (GNMT). When SAM rises after a protein-heavy meal, GNMT dumps the extra methyl groups onto glycine, making sarcosine, which is harmlessly broken down again. GNMT is one of the most abundant proteins in liver, and it's the main way SAM levels are kept in check.³ Glycine is the substrate. If glycine runs short, the valve works less well.

Muscle meat is high in methionine and low in glycine. Glycine-rich collagen (skin, connective tissue, bones) mostly went missing from the modern diet. In rats fed extra methionine, adding glycine or serine to the same diet prevented the rise in blood homocysteine and the build-up of methionine products in the liver. When glycine was added to an ongoing high-methionine diet, homocysteine fell within a day.⁴ That's the basis for pairing a lot of muscle meat with glycine or collagen. See Glycine / Collagen.

Methionine restriction. Rats fed 80% less methionine lived about 30% longer.⁵ Similar effects have been seen in several other species. In a small human trial in 26 adults with metabolic syndrome, 16 weeks of severe methionine restriction increased fat burning and lowered liver fat compared with a control diet.⁶ The diet is hard to follow, needs specially formulated foods and has no long-term human outcome data. Raising glycine is the practical version of the same idea: it doesn't cut methionine, it improves how the body handles it.

Intake

The requirement for methionine plus cysteine together is about 15 mg/kg/day, roughly 1 g/day for a 70 kg adult. Any diet with enough protein covers it easily. Animal proteins have about twice the methionine of most legumes.

Top foods

• Salmon or tuna: about 0.6–0.8 g in 3 oz
• Beef: about 0.6–0.7 g in 3 oz
• Chicken thigh: about 0.6 g in 3 oz
• Eggs: about 0.2 g each
• Yogurt (Greek): about 0.3 g per 6 oz

Deficiency effects

Methionine deficiency on its own is essentially only seen with very low-protein diets or protein malnutrition, where it contributes to poor growth, muscle loss, fatty liver and poor tissue repair. In practice the more common imbalance is the other way round: a lot of methionine relative to glycine and to the folate, B12 and B6 needed to process it, which shows up as raised homocysteine.