Serin: the pathway in the body · Biomarker & Blood Analysis

Serin is part of the pathway “Glycine and serine”. This page shows the whole pathway; the station of Serin is highlighted.

Where this laboratory value sits: Serine — amino acid. The phosphatase PSPH removes the phosphate group, forming serine. Serine also comes from food and from the breakdown of the body’s own proteins. When little serine is available, the cell makes more itself. Source 1

In brief

Glycine and serine are amino acids that the body can also make itself. They supply one-carbon units and are building blocks of proteins, membranes and glutathione. Serine hydroxymethyltransferase links the two and so feeds the folate cycle.

The pathway step by step

Each station states what the compound does there. Three signs: ↑ supplies — builds up or makes available · ↓ depletes — inhibits, consumes or withholds · ↕ both, depending on amount. Behind it stands what the statement rests on: established physiology, observed in studies, or contested. The signs do not grade; they name the direction.

1. 3-Phosphoglycerate → 3-Phosphohydroxypyruvate PHGDH · NAD⁺ Phosphoglycerate dehydrogenase (PHGDH) turns the OH group into a keto group and transfers the hydrogen to NAD⁺. This step sets the pace of the serine pathway. Source 1↑ supplies The first step sets the pace of the whole serine pathway: PHGDH determines how much carbon from sugar breakdown goes towards serine. In the process NAD⁺ becomes NADH. established physiology Source 1
   ⚖ When the balance tips

   too much — If PHGDH makes a lot of 3-phosphohydroxypyruvate, PSAT1 passes it on quickly; the intermediate hardly accumulates, and the flow towards serine rises.

   too little — If little NAD⁺ is free or PHGDH works slowly, little 3-phosphohydroxypyruvate forms, and the whole serine pathway from sugar runs more slowly.

   established physiology · Source 1

2. 3-Phosphohydroxypyruvate → 3-Phosphoserine PSAT1 · Vitamin B6 (PLP), Glutamate The aminotransferase PSAT1 transfers an amino group from glutamate to the molecule. It works with pyridoxal phosphate, the active form of vitamin B6. The glutamate becomes α-ketoglutarate. Source 1↑ supplies PSAT1 swaps nitrogen: glutamate gives up its amino group and becomes α-ketoglutarate, an intermediate of the citric acid cycle. This step thus links serine formation and nitrogen balance. established physiology Source 1
   ⚖ When the balance tips

   too much — If a lot runs through PSAT1, a correspondingly large amount of glutamate is converted to α-ketoglutarate; the step thus ties serine formation to the glutamate pool.

   too little — If little vitamin B6 or glutamate is available, PSAT1 cannot keep up, and less 3-phosphoserine forms for the last step.

   established physiology · Source 1

3. 3-Phosphoserine → Serine PSPH · Magnesium The phosphatase PSPH removes the phosphate group, forming serine. Serine also comes from food and from the breakdown of the body’s own proteins. When little serine is available, the cell makes more itself. Source 1↑ supplies Serine is a distributor: it supplies the one-carbon unit for the folate cycle and the skeleton for glycine, cysteine and membrane lipids. In many cells it is the main source of one-carbon units. established physiology Source 2, 1
   ⚖ When the balance tips

   too much — If plenty of serine is available, it covers glycine formation and the folate cycle; a dehydratase breaks the excess down to pyruvate, which enters energy metabolism.

   too little — If little serine is available, less is ready for glycine, one-carbon units and sphingolipids; the cell then makes more serine itself from 3-phosphoglycerate.

   established physiology · Source 1, 3

4. Serine → Glycine SHMT · Vitamin B6 (PLP), THF (folate) Serine hydroxymethyltransferase (SHMT) removes a one-carbon unit from serine and transfers it to tetrahydrofolate. Glycine remains. The step is reversible. Source 2, 3↑ supplies The SHMT reaction is reversible: depending on conditions it turns serine into glycine and a one-carbon unit, or glycine back into serine. This links both pools closely. established physiology Source 2, 3
   ⚖ When the balance tips

   too much — If glycine builds up, the glycine cleavage system breaks down the excess in the mitochondrion, or SHMT turns it back into serine.

   too little — If little glycine is available, it is first distributed to the building-block pathways; according to calculations in the reviews, the body’s own production does not always fully cover the demand for collagen, glutathione and haem.

   observed in studies · Source 3, 4

5. Glycine → Glycine as a component Glycine is a building block of glutathione, haem and creatine and is also attached to bile acids. In the collagen of connective tissue, every third position in the chain is a glycine. This uses up glycine. Source 4, 3↑ supplies As a building block glycine is used up: with cysteine and glutamate it forms glutathione, with succinyl-CoA the precursor of haem, with arginine the precursor of creatine. established physiology Source 4, 3
   ⚖ When the balance tips

   too much — If plenty of glycine is available, these syntheses run up to the limit of their enzymes; whatever exceeds that is broken down by the glycine cleavage system.

   too little — If little glycine is available, collagen, glutathione, haem and creatine draw on the same pool; in studies less glutathione is then formed.

   observed in studies · Source 4, 3

6. Glycine cleavage system → 5,10-Methylene-THF Glycine cleavage · THF (folate), NAD⁺ The one-carbon unit is now attached to tetrahydrofolate. From there it is used to build DNA components and to form methyl groups. Both routes draw on the same unit. Source 2↑ supplies 5,10-Methylene-THF is a switch point: thymidylate synthase builds the unit into DNA components, and MTHFR turns it into 5-methyl-THF for making methionine and methyl groups. established physiology Source 2
   ⚖ When the balance tips

   too much — If plenty of methylene-THF is available, DNA component synthesis and methylation run side by side; via SHMT the unit can also be transferred back to glycine, forming serine.

   too little — If little methylene-THF is available, DNA components and methyl groups draw on the same unit; less thymidine forms, and uracil is more likely to be built into DNA in its place.

   established physiology · Source 2

Further stations

• 3-Phosphoglycerate — from sugar breakdown The breakdown of glucose yields 3-phosphoglycerate. Part of it is diverted and serves as the starting material for serine. How much is diverted is set mainly by the first enzyme, PHGDH. Source 1↑ supplies 3-Phosphoglycerate is the branch point from sugar breakdown: what goes into the serine pathway here becomes the carbon skeleton for serine, glycine and one-carbon units instead of energy. established physiology Source 1
  ⚖ When the balance tips

  too much — If a lot of 3-phosphoglycerate arrives, most of it continues in sugar breakdown; how much branches into the serine pathway is set mainly by the amount of PHGDH.

  too little — If little 3-phosphoglycerate is available, the cell makes less serine itself and relies more on serine from food and from the breakdown of the body’s own proteins.

  established physiology · Source 1

• Sphingolipids — membrane components Serine is a building block of phosphatidylserine and, together with a fatty acid, the starting material for sphingolipids. Via cystathionine it also leads to cysteine. With little serine, fewer of them form. Source 1, 3↑ supplies Serine supplies the backbone of sphingolipids and the head group of phosphatidylserine; both are part of cell membranes. Via cystathionine it also passes its carbon skeleton on to cysteine. established physiology Source 1, 3
  ⚖ When the balance tips

  too much — More serine does not bring unlimited membrane lipids; the pace is set by the enzymes that link serine with fatty acids and head groups.

  too little — If little serine is available, fewer sphingolipids and less phosphatidylserine form, and less serine flows via cystathionine to cysteine.

  established physiology · Source 1, 3

• Glycine cleavage system — in the mitochondrion A complex of four proteins splits glycine into carbon dioxide, ammonia and a one-carbon unit. It works with vitamin B6, lipoic acid and tetrahydrofolate. It is the main breakdown route for glycine. Source 3, 2↑ supplies The cleavage system uses up glycine and in return supplies a one-carbon unit to tetrahydrofolate; carbon dioxide and ammonia are released, and NAD⁺ becomes NADH. established physiology Source 3, 2
  ⚖ When the balance tips

  too much — If the cleavage system is very active, more glycine is broken down and more ammonia is released, which the liver disposes of via the urea cycle.

  too little — If the cleavage system is barely active, glycine builds up in blood and tissue, because its main breakdown route hardly runs.

  established physiology · Source 4, 3

Cofactors in this pathway

• Vitamin B6 (PLP) — Cofactor of PSAT1, serine hydroxymethyltransferase and the glycine cleavage system; with little PLP, the pathway stalls Source 1, 2In the ORY catalogue as a laboratory value: Vitamin B6
• Folate (THF) — As tetrahydrofolate, accepts the one-carbon unit from serine and glycine; without THF no glycine from serine Source 2In the ORY catalogue as a laboratory value: Folsäure
• NAD⁺ — Accepts hydrogen at PHGDH and in the glycine cleavage system and becomes NADH in the process Source 1, 2In the ORY catalogue as a laboratory value: NAD⁺ (Nicotinamidadenindinukleotid)
• Glutamate — Donates the amino group for 3-phosphoserine at PSAT1 and becomes α-ketoglutarate Source 1In the ORY catalogue as a laboratory value: Glutamat
• Magnesium — Metal ion of the phosphatase PSPH, which turns 3-phosphoserine into serine; without it, the phosphate stays attached Source 1In the ORY catalogue as a laboratory value: Magnesium
• Lipoic acid — Bound to a protein of the glycine cleavage system, where it passes on intermediates; without it glycine breakdown stalls Source 3

Sources

1. Murtas G, Marcone GL, Sacchi S et al. L-serine synthesis via the phosphorylated pathway in humans. Cell Mol Life Sci 2020 · PubMed 32594192
2. Ducker GS, Rabinowitz JD. One-Carbon Metabolism in Health and Disease. Cell Metab 2017 · PubMed 27641100
3. Holeček M. Glycine as a conditionally essential amino acid and its relationship to l-serine. Metabolism 2025 · PubMed 40527450
4. Wang W, Wu Z, Dai Z et al. Glycine metabolism in animals and humans: implications for nutrition and health. Amino Acids 2013 · PubMed 23615880

Whole pathway: Glycine and serine

Related pathways

• Folic acid — 5,10-methylene-thf
• Methylation: methionine and homocysteine — 5,10-methylene-thf
• Alanine — Vitamin B6, NAD⁺ (Nicotinamidadenindinukleotid)
• GABA, glutamate and glutamine — Vitamin B6, NAD⁺ (Nicotinamidadenindinukleotid)
• Dopamine, noradrenaline, adrenaline — Vitamin B6, NAD⁺ (Nicotinamidadenindinukleotid)

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
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