8-OHdG: the pathway in the body · Biomarker & Urine Analysis

This page shows the biochemical pathway behind the laboratory value 8-OHdG (8-hydroxy-2'-deoxyguanosine): which stations follow one another, which enzymes carry out each step and which cofactors they use. Every statement has a source. The page describes general textbook knowledge and says nothing about any individual person.

In brief

8-OHdG is a fragment of the DNA base guanine that has been oxidised by oxygen radicals. Cells cut such building blocks out of DNA or remove them from the nucleotide pool; the fragments pass into the urine. Oxidised guanine readily pairs with adenine.

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. Oxygen → Superoxide Respiratory chain When oxygen picks up a single electron, superoxide forms – a radical, meaning a molecule with an unpaired electron. It attacks iron-sulphur centres in enzymes. Source 1↕ both, depending on amount Superoxide readily passes on its unpaired electron; it attacks iron-sulphur centres in enzymes and releases iron in the process. In small amounts it also serves as a signal via hydrogen peroxide. observed in studies Source 1, 2
   ⚖ When the balance tips

   too much — If superoxide builds up because the dismutases cannot keep pace, more iron-sulphur centres are attacked; the iron released becomes available for the Fenton reaction.

   too little — If little superoxide forms, little hydrogen peroxide arises either, which cells use in small amounts as a messenger.

   observed in studies · Source 1, 2

2. Superoxide → Hydrogen peroxide SOD1, SOD2 · Manganese, Copper and zinc The superoxide dismutases convert two superoxide molecules into hydrogen peroxide and oxygen. SOD2 works in the mitochondrion with manganese, SOD1 in the cytoplasm with copper and zinc. In small amounts it serves as a messenger. Source 2↕ both, depending on amount Hydrogen peroxide is not a radical and crosses membranes; in small amounts it serves as a messenger. If it meets free Fe²⁺, the hydroxyl radical forms; how much free iron is present decides which route prevails. observed in studies Source 2, 3
   ⚖ When the balance tips

   too much — If hydrogen peroxide builds up because catalase and glutathione peroxidase cannot keep pace, it spreads further through the cell, and more hydroxyl radicals form at free iron.

   too little — If little hydrogen peroxide is present, its signal is weaker, and hardly any hydroxyl radicals form at iron.

   observed in studies · Source 2, 3

3. Hydrogen peroxide → Water Catalase, GPx · Glutathione, Selenium Catalase and glutathione peroxidase break hydrogen peroxide down into water. Glutathione peroxidase carries selenium in its active site. It is then no longer available for the Fenton reaction. Source 2↓ depletes By breaking the peroxide down into water, the cell withdraws it from the Fenton reaction. Glutathione peroxidase uses up glutathione in the process, which the cell reduces again with NADPH. established physiology Source 2
   ⚖ When the balance tips

   too much — If catalase and glutathione peroxidase work very hard, the hydrogen peroxide that serves as a messenger is also intercepted, and more glutathione is oxidised.

   too little — If little selenium or glutathione is available, glutathione peroxidase breaks down less peroxide; more of it remains for the Fenton reaction.

   observed in studies · Source 2, 3

4. Hydrogen peroxide → Hydroxyl radical Fenton reaction · Iron (Fe²⁺) When hydrogen peroxide meets ferrous iron, the hydroxyl radical forms. It reacts at once with whichever molecule lies closest. This route is called the Fenton reaction. It oxidises fats, proteins and DNA. Source 3↓ depletes The hydroxyl radical reacts with almost any molecule close by: it removes electrons from fats, proteins and DNA or attaches to them. Because it reacts so quickly, it acts only where it forms. established physiology Source 3
   ⚖ When the balance tips

   too much — If many hydroxyl radicals form near DNA, more guanine building blocks are oxidised, and OGG1 and MTH1 have more to remove.

   too little — If few hydroxyl radicals form, for example because little free Fe²⁺ is present, DNA, fats and proteins remain largely unchanged.

   observed in studies · Source 3, 4

5. Hydroxyl radical → 8-oxo-dG in DNA Of the four building blocks of DNA, guanine is the most easily oxidised. It becomes 8-oxo-dG, an altered base that the cell recognises as damage. During copying it readily pairs with adenine. Source 4↓ depletes When DNA is copied, 8-oxo-dG readily pairs with adenine instead of cytosine. If it stays in place, a wrong building block thus enters the new strand at the next copying. established physiology Source 4, 5
   ⚖ When the balance tips

   too much — If more 8-oxo-dG forms than OGG1 cuts out, it stays in the strand longer, and adenine mispairs enter new strands more often during copying.

   too little — If little 8-oxo-dG forms, OGG1 has little to cut out, and fewer fragments arise for the urine.

   observed in studies · Source 4, 5

6. 8-oxo-dGTP → 8-oxo-dGMP MTH1 (NUDT1) The enzyme MTH1 removes two phosphate groups from the oxidised building block. It then no longer fits into DNA and has left the pool. In this way it does not enter newly made DNA. Source 5↓ depletes With the cleavage by MTH1, the cell withdraws the oxidised building block from the pool before the polymerase builds it in. The cleaved form can no longer enter DNA. observed in studies Source 5
   ⚖ When the balance tips

   too much — If MTH1 splits a lot, the pool remains largely free of oxidised building blocks, and more 8-oxo-dGMP arises.

   too little — If MTH1 is not very active, more oxidised building blocks remain in the pool; in animal models without MTH1, more 8-oxo-dG is found in DNA.

   observed in studies · Source 5

7. 8-oxo-dGMP → 8-OHdG Nucleotidase A nucleotidase removes the last phosphate group. What remains is the nucleoside 8-OHdG, which the cell does not convert any further. It leaves the cell via the blood. Source 5, 4↓ depletes The last cleavage turns the oxidised building block into a nucleoside that the cell does not convert any further but releases into the blood. In this way the damage leaves the pool for good. observed in studies Source 5, 4
   ⚖ When the balance tips

   too much — If MTH1 and the nucleotidase break down many oxidised building blocks, more 8-OHdG arises, and more of it reaches the blood and the urine.

   too little — If few oxidised building blocks are broken down from the pool, little 8-OHdG arises, and correspondingly little reaches the urine.

   observed in studies · Source 5, 4

8. 8-OHdG → In urine Both fragments pass into the blood and are excreted via the kidneys. How much comes from the DNA strand and how much from the pool of building blocks has not been fully resolved. They enter no further reaction. Source 4, 5↓ depletes The fragments leave the body unchanged via the kidneys; they are neither broken down nor reused. established physiology Source 4
   ⚖ When the balance tips

   too much — If many fragments reach the blood, the kidneys excrete more of them; which of the two routes they come from cannot be separated in the urine.

   too little — If few fragments reach the blood, the urine contains correspondingly few; the kidneys excrete only what arrives in the blood.

   established physiology · Source 4

9. 8-oxoguanine → In urine via blood and kidney Both fragments pass into the blood and are excreted via the kidneys. How much comes from the DNA strand and how much from the pool of building blocks has not been fully resolved. They enter no further reaction. Source 4, 5↓ depletes The fragments leave the body unchanged via the kidneys; they are neither broken down nor reused. established physiology Source 4
   ⚖ When the balance tips

   too much — If many fragments reach the blood, the kidneys excrete more of them; which of the two routes they come from cannot be separated in the urine.

   too little — If few fragments reach the blood, the urine contains correspondingly few; the kidneys excrete only what arrives in the blood.

   established physiology · Source 4

Further stations

• Oxygen — in the mitochondria In the mitochondria, electrons flow through the respiratory chain. A small share of them meets oxygen directly along the way. At the end of the chain it becomes water. Source 1↑ supplies Oxygen is the final acceptor of electrons in the respiratory chain; water forms, and the mitochondria gain the energy for ATP. Only a small share of electrons meets oxygen prematurely. established physiology Source 1
  ⚖ When the balance tips

  too much — If plenty of oxygen is available and the respiratory chain is heavily loaded with electrons, more electrons meet oxygen prematurely, and more superoxide forms.

  too little — If little oxygen is available, fewer molecules accept electrons at the end of the chain, and the mitochondria gain less energy for ATP.

  observed in studies · Source 1

• 8-oxo-dGTP — free building block, oxidised Loose building blocks in the cell fluid are oxidised too. If 8-oxo-dGTP were built in, the damage would sit directly in the newly made DNA. MTH1 intercepts such building blocks beforehand. Source 5↓ depletes DNA polymerase can insert oxidised free building blocks opposite adenine. In this way the damage enters newly made DNA directly. observed in studies Source 5
  ⚖ When the balance tips

  too much — If more oxidised building blocks arise than MTH1 can split, more of them are built into newly made DNA.

  too little — If little of the pool is oxidised, the pool of building blocks remains largely undamaged, and MTH1 has little to split.

  observed in studies · Source 5

• 8-oxoguanine — excised base The enzyme OGG1 recognises the altered base in the DNA strand and cuts it out. Other enzymes fill the gap with an undamaged building block. In this way the DNA strand is restored. Source 4↑ supplies Excision by OGG1 starts base excision repair: a polymerase then fills the gap with guanine, and a ligase closes the strand again. established physiology Source 4
  ⚖ When the balance tips

  too much — If OGG1 cuts out many bases, more 8-oxo-guanine reaches the blood and the urine.

  too little — If OGG1 is not very active, 8-oxo-dG stays in the DNA strand longer, and adenine mispairs enter new strands more often during copying.

  observed in studies · Source 4, 5

Cofactors in this pathway

• Selenium — Component of glutathione peroxidase, which breaks hydrogen peroxide down to water before the Fenton reaction uses it Source 2In the ORY catalogue as a laboratory value: Selen
• Glutathione — Supplies glutathione peroxidase with the electrons used to break down peroxides; it is itself oxidised in the process Source 2In the ORY catalogue as a laboratory value: Glutathion (GSH)
• Manganese — Metal at the centre of SOD2, which converts superoxide in the mitochondrion; this yields hydrogen peroxide Source 2
• Copper — Metal at the centre of SOD1, which converts superoxide in the cytosol; this yields hydrogen peroxide Source 2In the ORY catalogue as a laboratory value: Kupfer (Cu)
• Zinc — Second metal of SOD1; holds the structure of the enzyme; so SOD1 can convert superoxide Source 2In the ORY catalogue as a laboratory value: Zink
• Iron — Haem iron of catalase; free Fe²⁺ forms hydroxyl radicals in the Fenton reaction; these oxidise guanine Source 2, 3In the ORY catalogue as a laboratory value: Eisen
• Vitamin C — Water-soluble antioxidant that intercepts radicals by donating electrons; it is itself oxidised in the process Source 2In the ORY catalogue as a laboratory value: Vitamin C (Ascorbinsäure)

Sources

1. Murphy MP. How mitochondria produce reactive oxygen species. Biochem J 2009 · PubMed 19061483
2. Jomova K, Alomar SY, Alwasel SH et al. Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants. Arch Toxicol 2024 · PubMed 38483584
3. Wardman P, Candeias LP. Fenton chemistry: an introduction. Radiat Res 1996 · PubMed 8619017
4. Cooke MS, Olinski R, Loft S. Measurement and meaning of oxidatively modified DNA lesions in urine. Cancer Epidemiol Biomarkers Prev 2008 · PubMed 18199707
5. Nakabeppu Y, Ohta E, Abolhassani N. MTH1 as a nucleotide pool sanitizing enzyme: Friend or foe? Free Radic Biol Med 2017 · PubMed 27833032

Related pathways

• Antioxidant capacity — superoxide
• Glutathione — hydrogen peroxide
• Selenium — hydrogen peroxide
• Copper — Glutathion (GSH), Zink
• Vitamin C — Selen, Glutathion (GSH)

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