Blei: the pathway in the body · Biomarker & Laboratory Analysis

Blei is part of the pathway “Blei”. This page shows the whole pathway; the station of Blei is highlighted.

Where this laboratory value sits: Lead in food and air — via gut and lung. Lead reaches the gut with food and drinking water, or the lung as fine dust. From the lung it passes quickly into the blood. More passes over from the lung than from the gut. Source 1, 2

In brief

Lead is a heavy metal with no known role in the body. It enters via gut and lung, is carried in the erythrocytes, stored in bone in place of calcium, and inhibits enzymes of haem formation. Haem precursors then build up.

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. Lead in food and air → Into the gut cell DMT1 In the gut, lead uses transport routes of other metals: the iron transporter DMT1 and uptake routes for calcium. This is called ionic mimicry. It thus competes with iron and calcium. Source 1↑ supplies DMT1 and calcium routes deliver lead into the gut cell because, as a divalent ion, it resembles iron and calcium. established physiology Source 1
   ⚖ When the balance tips

   too much — If there is a lot of lead in the gut, it uses these routes more and competes there with iron and calcium.

   too little — If there is little lead in the gut, the transporters carry almost only iron and calcium; if these two are scarce, more of the routes are made and they also absorb lead more readily.

   observed in studies · Source 1

2. Into the gut cell → Lead in blood In blood, lead sits almost entirely in the red blood cells (erythrocytes), mainly bound to the enzyme ALAD. Only a small part moves freely in plasma. Only the free part reaches the tissues. Source 2↑ supplies In the red blood cells lead binds to ALAD and is distributed around the body in this way; only the small free share in plasma reaches tissues and bone. established physiology Source 2
   ⚖ When the balance tips

   too much — If lead in the blood rises, the binding sites in the red blood cells become increasingly occupied, and the free share in plasma grows disproportionately.

   too little — If there is little lead in the blood, almost all of it is bound in the red blood cells, and only very little remains free in plasma.

   observed in studies · Source 2

3. Lead in blood → Bone · instead of calcium Lead is built into bone mineral in place of calcium. Bone is the largest store; during bone remodelling it slowly releases lead back into the blood. It thus keeps supplying lead for years. Source 3, 2↓ depletes Bone mineral withdraws lead from the blood and stores it for years; during bone remodelling it releases part of it again, so bone keeps resupplying lead for a long time. established physiology Source 3, 2
   ⚖ When the balance tips

   too much — If a lot of lead is stored in bone, more of it returns to the blood during bone remodelling, especially at times of increased remodelling.

   too little — If little lead is stored in bone, bone remodelling resupplies hardly any lead, and the amount in the blood mainly follows current intake.

   established physiology · Source 3

4. Lead in blood → Kidney From plasma, lead reaches soft tissues such as kidney and liver and binds to metallothionein there. It leaves the body mainly with the urine, a small part via the bile. Excretion is slow. Source 2, 7↓ depletes Metallothionein in kidney and liver binds part of the lead; it leaves the body via the urine and, to a small extent, via the bile. established physiology Source 2, 7
   ⚖ When the balance tips

   too much — If there is a lot of lead in kidney and liver, more metallothionein is occupied; unbound lead remains in the cells and binds to other sulphur groups.

   too little — If little lead is there, the existing metallothionein is enough to bind it, and excretion stays low.

   observed in studies · Source 2, 7

5. 5-Aminolevulinic acid → Porphobilinogen ALAD · Zinc ALA dehydratase (ALAD) joins two molecules of ALA into porphobilinogen. Lead inhibits exactly this step; ALA is then not converted further. Haem formation then stalls. Source 4, 8↑ supplies Porphobilinogen supplies the building blocks, four of which together form the haem ring. ALAD, which makes it, responds even to small amounts of lead. established physiology Source 4, 8
   ⚖ When the balance tips

   too much — If plenty of porphobilinogen is present, it is promptly processed further into protoporphyrin IX.

   too little — If little porphobilinogen forms because lead inhibits ALAD, haem formation stalls at this point, and ALA is left over.

   established physiology · Source 4, 8

6. Porphobilinogen → Protoporphyrin IX several enzymes Several enzymes build the ring protoporphyrin IX from porphobilinogen. The last steps run in the mitochondrion. The ring is the framework of haem. Source 8↑ supplies Protoporphyrin IX is the finished ring into which only the metal still has to be inserted; it supplies the framework of haem. established physiology Source 8
   ⚖ When the balance tips

   too much — If protoporphyrin IX builds up because ferrochelatase is inhibited or little iron is available, zinc is inserted more often.

   too little — If little protoporphyrin IX forms, ferrochelatase makes little haem, even when iron is plentiful.

   established physiology · Source 8, 5

7. Protoporphyrin IX → Haem Ferrochelatase · Iron Ferrochelatase inserts iron into protoporphyrin IX; this forms haem, the pigment of haemoglobin. Lead also inhibits this enzyme. Haem slows its own formation. Source 8, 4↑ supplies Haem is the centre of haemoglobin, which binds oxygen, and of many enzymes such as the cytochromes; at the same time it slows its own formation at ALA synthase. established physiology Source 8, 4
   ⚖ When the balance tips

   too much — If plenty of haem is present, it throttles ALA synthase, and the cell makes fewer new precursors.

   too little — If little haem forms, for example because lead inhibits ALAD and ferrochelatase, ALA synthase is slowed less, and precursors build up before the inhibited steps.

   established physiology · Source 8, 4

8. Protoporphyrin IX → Zinc protoporphyrin Ferrochelatase · Zinc When ferrochelatase does not work with iron, it inserts zinc into protoporphyrin IX. This forms zinc protoporphyrin, which stays in the red blood cells. It does not bind oxygen. Source 5↓ depletes Zinc protoporphyrin does not bind oxygen; every molecule of it is protoporphyrin IX that does not become haem. It stays in the red blood cells for their lifetime. established physiology Source 5
   ⚖ When the balance tips

   too much — If a lot of zinc protoporphyrin forms, it accumulates in the red blood cells and stays there until they are broken down after a few months.

   too little — If little zinc protoporphyrin forms, almost every protoporphyrin IX has been completed with iron to form haem.

   established physiology · Source 5

Further stations

• Lead in food and air — via gut and lung Lead reaches the gut with food and drinking water, or the lung as fine dust. From the lung it passes quickly into the blood. More passes over from the lung than from the gut. Source 1, 2↑ supplies Food, drinking water and inhaled dust supply lead; from the lung it passes into the blood faster and more completely than from the gut. established physiology Source 1, 2
  ⚖ When the balance tips

  too much — If more lead arrives, the amount in the red blood cells rises with it within weeks; part of it moves on into bone.

  too little — If little lead arrives, the amount in the blood falls over weeks; lead from bone then continues to be resupplied slowly.

  established physiology · Source 2

• Lead in the cell — binds to SH groups Inside the cell, lead binds to sulfhydryl groups (SH groups) of proteins and of glutathione. It also occupies binding sites that normally hold zinc or calcium. Less glutathione is then available. Source 6, 1↓ depletes Lead occupies SH groups of proteins and glutathione as well as binding sites for zinc and calcium; the proteins concerned then work differently, and less glutathione is available. observed in studies Source 6, 1
  ⚖ When the balance tips

  too much — If there is a lot of lead in the cell, more glutathione is bound; in studies the balance shifts towards oxidised forms, and reactive oxygen species increase.

  too little — If there is little lead in the cell, glutathione and the binding sites for zinc and calcium remain mostly free for their own tasks.

  observed in studies · Source 6

• Zinc — cofactor of ALAD The enzyme ALAD carries zinc in its active site, bound to cysteines. Lead takes this place, and the enzyme then stops working. With little zinc present, lead manages this more easily. Source 4, 8↑ supplies Zinc in the active site makes ALAD functional; it holds the cysteines in the shape in which the enzyme joins two ALA molecules. established physiology Source 4, 8
  ⚖ When the balance tips

  too much — If plenty of zinc is present, it occupies the binding site more often, and lead displaces it less easily; in laboratory assays zinc partly restores ALAD activity.

  too little — If little zinc is present, the binding site is empty more often, and lead can occupy it more easily.

  observed in studies · Source 4

• 5-Aminolevulinic acid — ALA, first haem precursor ALA synthase joins succinyl-CoA and glycine to form 5-aminolaevulinic acid (ALA). This is the first step of haem formation; vitamin B6 is the cofactor. If ALA builds up, it passes into the urine. Source 8↑ supplies ALA supplies the building block from which all further stages of haem arise; ALA synthase sets how much of it is made. established physiology Source 8
  ⚖ When the balance tips

  too much — If ALA builds up because ALAD is inhibited, it passes into the blood and is excreted in the urine.

  too little — If little ALA forms, for example because vitamin B6 is scarce, less haem is made as well.

  established physiology · Source 8, 4

Cofactors in this pathway

• Zinc — Cofactor of ALAD; lead takes its place in the active site; this is easier when zinc is scarce Source 4, 8In the ORY catalogue as a laboratory value: Zink
• Iron — Ferrochelatase inserts iron into protoporphyrin IX; lead inhibits this step; zinc is then inserted Source 8, 5In the ORY catalogue as a laboratory value: Eisen
• Glutathione — Binds lead via its SH group inside the cell and is then unavailable for other tasks Source 6In the ORY catalogue as a laboratory value: Glutathion (GSH)
• Calcium — Lead uses uptake routes for calcium and takes its place in bone; it stays there for years Source 1, 3In the ORY catalogue as a laboratory value: Calcium (intrazellulär)
• Vitamin B6 — Cofactor of ALA synthase, which joins succinyl-CoA and glycine to form ALA; without ALA, no haem Source 8In the ORY catalogue as a laboratory value: Vitamin B6
• Glycine — Building block of 5-aminolaevulinic acid, the first precursor of haem Source 8In the ORY catalogue as a laboratory value: Glycin

Sources

1. Bridges CC, Zalups RK. Molecular and ionic mimicry and the transport of toxic metals. Toxicol Appl Pharmacol 2005 · PubMed 15845419
2. Barbosa F Jr, Tanus-Santos JE et al. A critical review of biomarkers used for monitoring human exposure to lead: advantages, limitations, and future needs. Environ Health Perspect 2005 · PubMed 16330345
3. Rabinowitz MB. Toxicokinetics of bone lead. Environ Health Perspect 1991 · PubMed 2040248
4. Warren MJ, Cooper JB et al. Lead poisoning, haem synthesis and 5-aminolaevulinic acid dehydratase. Trends Biochem Sci 1998 · PubMed 9644976
5. Labbé RF, Vreman HJ et al. Zinc protoporphyrin: A metabolite with a mission. Clin Chem 1999 · PubMed 10585337
6. Ahamed M, Siddiqui MK. Low level lead exposure and oxidative stress: current opinions. Clin Chim Acta 2007 · PubMed 17573057
7. Wong DL, Merrifield-MacRae ME et al. Lead(II) Binding in Metallothioneins. Met Ions Life Sci 2017 · PubMed 28731302
8. Ajioka RS, Phillips JD et al. Biosynthesis of heme in mammals. Biochim Biophys Acta 2006 · PubMed 16839620

Whole pathway: Blei

Related pathways

• Cadmium — Zink, Eisen
• Nickel — Zink, Eisen
• Quecksilber — Zink, Glutathion (GSH)

As of 2026-09-18. Draft, written by Claude to schema v2; sources checked in PubMed; expert approval pending
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