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

Arginin is part of the pathway “Arginine and nitric oxide”. This page shows the whole pathway; the station of Arginin is highlighted.

Where this laboratory value sits: Arginine — Amino acid. Argininosuccinate lyase splits off fumarate, leaving arginine. Arginine also comes from dietary protein and from the breakdown of the body's own proteins. It is the only starting material for NO. Source 2, 1

In brief

Nitric oxide (NO) is a short-lived gas that NO synthases form from the amino acid arginine. In the vessel wall it triggers relaxation of the muscle cells via the messenger cGMP; ADMA inhibits its formation. If NO meets superoxide, peroxynitrite forms.

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. Citrulline → Argininosuccinate ASS · Aspartate, ATP In the kidney, argininosuccinate synthetase links citrulline with the amino acid aspartate. This step uses ATP. It is the slowest step towards arginine. Source 1, 2↑ supplies Argininosuccinate is the intermediate through which citrulline receives a further nitrogen from aspartate. Its formation uses ATP and is the slowest step on the way to arginine. established physiology Source 2, 1
   ⚖ When the balance tips

   too much — If a lot of argininosuccinate forms, the lyase splits it quickly; more arginine and fumarate then result.

   too little — If little aspartate or ATP is available, the synthetase cannot keep pace, and less arginine forms from citrulline.

   established physiology · Source 2

2. Argininosuccinate → Arginine ASL Argininosuccinate lyase splits off fumarate, leaving arginine. Arginine also comes from dietary protein and from the breakdown of the body's own proteins. It is the only starting material for NO. Source 2, 1↑ supplies Arginine is the only starting material of NO synthase; arginase, protein synthesis and creatine synthesis also use it. Which pathway gets how much is decided within the individual cell. established physiology Source 2, 3
   ⚖ When the balance tips

   too much — If a lot of arginine is present, NO synthase is already working close to saturation and makes hardly any more NO; the excess goes mainly to arginase.

   too little — If little arginine is in the cell, for example because arginase draws off a lot of it, NO synthase makes less NO and, in studies, releases more superoxide.

   observed in studies · Source 2, 3

3. Arginine → Ornithine Arginase · Manganese Arginase splits arginine into ornithine and urea. It carries manganese in its active centre. Within the cell, arginase and NO synthase share the same arginine. What arginase splits is no longer available for NO. Source 2↓ depletes Arginase draws arginine away from NO synthase: what it splits into ornithine and urea is no longer available for NO. Ornithine itself is the starting material for polyamines and proline. established physiology Source 2
   ⚖ When the balance tips

   too much — If arginase is very active, arginine in the cell falls, and less starting material remains for NO synthase; in studies this goes along with lower NO formation.

   too little — If arginase is not very active, more arginine remains for NO synthase; at the same time less ornithine forms for polyamines and proline.

   observed in studies · Source 2, 3

4. Methylarginine → ADMA Protein breakdown When these proteins are broken down, the methylated arginine is released on its own: ADMA. It resembles arginine so closely that it fits into NO synthase and blocks it there. In this way it slows NO formation. Source 4, 5↓ depletes ADMA occupies the arginine binding site in NO synthase and so slows NO formation. How strongly it slows depends on its ratio to arginine in the cell, not on ADMA alone. established physiology Source 4, 5
   ⚖ When the balance tips

   too much — If ADMA builds up in the cell, for example because DDAH works more slowly, NO synthase makes less NO; in cell culture it also releases superoxide.

   too little — If little ADMA is present, arginine has the binding site of NO synthase largely to itself, and the brake on NO formation is weak.

   observed in studies · Source 4, 5

5. ADMA → Dimethylamine DDAH The enzyme DDAH splits ADMA into dimethylamine and citrulline. How much ADMA a cell contains therefore depends mainly on DDAH. This releases the brake on NO synthase. Source 4, 5↑ supplies With the breakdown by DDAH, the cell releases the brake on NO synthase. The citrulline set free can become arginine again. established physiology Source 4, 5
   ⚖ When the balance tips

   too much — If DDAH works very quickly, little ADMA remains, and NO synthase is hardly slowed.

   too little — If DDAH works slowly, ADMA accumulates in the cell and also passes into the blood; NO synthase is then slowed more strongly.

   observed in studies · Source 4, 5

6. Arginine → Nitric oxide NO synthase · BH4, NADPH NO synthase converts arginine to citrulline and releases NO. It needs oxygen, NADPH and the cofactor BH4; without enough BH4 it releases superoxide instead of NO. If NO meets superoxide, peroxynitrite forms. Source 3↕ both, depending on amount In small amounts NO is a signalling substance that widens vessels and keeps platelets quiet. If it meets superoxide, peroxynitrite forms, which oxidises proteins, fats and BH4. How much superoxide is present decides which route prevails. observed in studies Source 3
   ⚖ When the balance tips

   too much — If cells make a lot of NO, for example via inducible NO synthase in immune cells, and superoxide is present at the same time, more peroxynitrite forms, which alters proteins.

   too little — If little NO forms, for example because BH4 is scarce, guanylate cyclase in the vessel muscle stays less active, and the vessel widens less.

   observed in studies · Source 3

7. Nitric oxide → cGMP Guanylate cyclase · Haem iron, GTP NO enters the muscle cell of the vessel wall and binds there to the haem iron of soluble guanylate cyclase. The enzyme then converts GTP to cGMP. This passes on the brief NO signal. Source 6, 3↑ supplies cGMP translates the brief NO signal into an effect: when NO binds to the haem iron, guanylate cyclase works many times faster. Phosphodiesterases break cGMP down again and so end the signal. established physiology Source 6
   ⚖ When the balance tips

   too much — If a lot of cGMP is present, protein kinase G stays switched on longer; the muscle cell stays relaxed until phosphodiesterases have broken down the messenger.

   too little — If little cGMP forms, for example because little NO arrives or the haem iron is oxidised and no longer binds NO, protein kinase G is hardly switched on.

   established physiology · Source 6

8. cGMP → Vascular muscle Protein kinase G cGMP switches on protein kinase G. It lowers free calcium in the muscle cell, the cell relaxes, and the vessel widens. In this way the vessel wall adjusts blood flow. Source 6, 3↑ supplies When the vessel muscle relaxes, the vessel widens, and blood flows through with less resistance. In this way the vessel wall continuously adjusts blood flow to the needs of the tissue. established physiology Source 6, 3
   ⚖ When the balance tips

   too much — If many vessel muscles relax at once, many vessels widen at the same time, and the pressure in the vessels falls.

   too little — If the vessel muscle relaxes little, the vessel stays narrower, and blood flows against a higher resistance.

   established physiology · Source 3, 6

Further stations

• Citrulline — from the gut Citrulline is an amino acid that is not built into proteins. Gut cells make it from glutamine and release it into the blood; the kidney captures it again. From it the kidney makes arginine. Source 1↑ supplies Citrulline is the precursor from which the kidney makes arginine for the whole body. Because the liver takes up hardly any of it, it travels from the gut to the kidney largely unchanged. established physiology Source 1
  ⚖ When the balance tips

  too much — If a lot of citrulline reaches the kidney, it makes more arginine from it and releases it into the blood.

  too little — If little citrulline comes from the gut, the kidney makes less arginine; the body then relies more on arginine from food and protein breakdown.

  established physiology · Source 1

• Methylarginine — in proteins, via PRMT The enzyme PRMT attaches methyl groups from SAM to arginine units within proteins. This is part of the everyday fine-tuning of many proteins. ADMA later arises from this. Source 4↕ both, depending on amount Methylation by PRMT helps control the work of many proteins. At the same time it is the source of ADMA: what is methylated here slows NO synthase once the proteins are broken down. established physiology Source 4
  ⚖ When the balance tips

  too much — If the PRMTs methylate a lot, more ADMA is later released when the proteins are broken down.

  too little — If little methylation takes place, less ADMA is released during protein breakdown; at the same time many proteins carry fewer of the methyl groups that help control their work.

  established physiology · Source 4

Cofactors in this pathway

• Arginine — Starting material from which NO synthase forms NO and citrulline; arginase also uses it up Source 3In the ORY catalogue as a laboratory value: Arginin
• Tetrahydrobiopterin (BH4) — Cofactor of NO synthase; with little BH4 it releases superoxide instead of NO Source 3
• Riboflavin (FAD, FMN) — As FAD and FMN, electron carriers within NO synthase from NADPH to the haem Source 3
• Niacin (NADPH) — NADPH supplies NO synthase with electrons for converting arginine Source 3
• Iron — Haem iron in NO synthase and in guanylate cyclase, to which NO binds; NO binding switches the cyclase on Source 3, 6In the ORY catalogue as a laboratory value: Eisen
• Calcium — Activates NO synthase via calmodulin, once calcium rises in the endothelial cell Source 3In the ORY catalogue as a laboratory value: Calcium (intrazellulär)
• Manganese — Metal centre of arginase, which splits arginine into ornithine and urea; arginase competes for arginine Source 2
• Methionine (SAM) — As S-adenosylmethionine, provides PRMT with the methyl groups for ADMA; ADMA later slows NO synthase Source 4In the ORY catalogue as a laboratory value: Methionin

What acts on this pathway

• Glyceryl trinitrate — Glyceryl trinitrate releases nitric oxide in the body, which switches on the same guanylate cyclase as the body's own NO. The prescribing information describes this mechanism. Source 7

Sources

1. Curis E, Nicolis I et al. Almost all about citrulline in mammals. Amino Acids 2005 · PubMed 16082501
2. Morris SM Jr. Enzymes of arginine metabolism. J Nutr 2004 · PubMed 15465778
3. Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J 2012 · PubMed 21890489
4. Pope AJ, Karuppiah K et al. Role of the PRMT-DDAH-ADMA axis in the regulation of endothelial nitric oxide production. Pharmacol Res 2009 · PubMed 19682581
5. Teerlink T, Luo Z et al. Cellular ADMA: regulation and action. Pharmacol Res 2009 · PubMed 19682580
6. Derbyshire ER, Marletta MA. Structure and regulation of soluble guanylate cyclase. Annu Rev Biochem 2012 · PubMed 22404633
7. US prescribing information Nitroglycerin (DailyMed), section Clinical Pharmacology, Mechanism of Action · Prescribing information

Whole pathway: Arginine and nitric oxide

Related pathways

• Nitrosative stress — nitric oxide
• Spermidine — ornithine
• Granulocytes in the gut wall — Eisen, Calcium (intrazellulär)
• Calprotectin — Eisen, Calcium (intrazellulär)
• Carnitine — Eisen, Methionin

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