Definition
Description
Top Gene Interactions
Related Pathways
General Information
- Metabolism: Lead is absorbed following inhalation, oral, and dermal exposure. It is then distributed mainly to the bones and red blood cells. In the blood lead may be found bound to serum albumin or the metal-binding protein metallothionein. Organic lead is metabolized by cytochrome P-450 enzymes, whereas inorganic lead forms complexes with delta-aminolevulinic acid dehydratase. Lead is excreted mainly in the urine and faeces. (L136)
- Uses/Sources: Lead is used extensively in building construction and can also be found in batteries, ammunition, non-Western cosmetics, solder, and pipes. Old paints and ceramic products may also contain lead, though recent legislation has banned its use. (L136)
- Health Effects: Lead is a neurotoxin and has been known to cause brain damage and reduced cognitive capacity, especially in children. Lead exposure can result in nephropathy, as well as blood disorders such as high blood pressure and anemia. Lead also exhibits reproductive toxicity and can results in miscarriages and reduced sperm production. (L21)
- Symptoms: Symptoms of chronic lead poisoning include reduced cognitive abilities, nausea, abdominal pain, irritability, insomnia, metal taste in the mouth, excess lethargy or hyperactivity, chest pain, headache and, in extreme cases, seizures, comas, and death. There are also associated gastrointestinal problems, such as constipation, diarrhea, vomiting, poor appetite, weight loss, which are common in acute poisoning. (A2, L21)
- Treatment: Lead poisoning is usually treated with chelation therapy using DMSA, EDTA, or dimercaprol. (L21)
- Route of Exposure: Oral (L136) ; inhalation (L136) ; dermal (L136)
Toxicity
- Carcinogenicity: 2B, possibly carcinogenic to humans. (L135)
- Toxicity: At blood lead levels between 25 and 60 μg/dL, neuropsychiatric effects such as delayed reaction times, irritability, and difficulty concentrating, as well as slowed motor nerve conduction and headache can occur. Anemia may appear at blood lead levels higher than 50 μg/dL. In adults, Abdominal colic, involving paroxysms of pain, may appear at blood lead levels greater than 80 μg/dL.
- Lethal Dose: 714 mg/kg of lead acetate (i.e., about 450 mg/kg of lead) is the lethal oral dose. An oral dose of 450 mg Pb/kg is equivalent to a 70-kg worker being exposed to 21,000 mg Pb/m3 for 30 minutes, assuming a breathing rate of 50 L/minute and 100% absorption.
- Minimum Risk Level: Chronic Inhalation: 0.05 mg/m3 (L134)
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
Sodium/potassium-transporting ATPase subunit alpha-1 Sodium/potassium-transporting ATPase subunit alpha-2 Sodium/potassium-transporting ATPase subunit alpha-3 Sodium/potassium-transporting ATPase subunit alpha-4 Sodium/potassium-transporting ATPase subunit beta-1 Sodium/potassium-transporting ATPase subunit beta-2 Sodium/potassium-transporting ATPase subunit beta-3 Sodium/potassium-transporting ATPase subunit gamma |
Lead binds to sodium/potassium-transporting ATPases. (A24) |
1664209 |
Delta-aminolevulinic acid dehydratase | Lead inhibition of ALAD prevents the biosynthesis of heme, which is a necesssary cofactor of hemoglobin. (L21) |
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DNA | The ionizing radiation produced by lead-210 causes cellular damage that includes DNA breakage, accurate or inaccurate repair, apoptosis, gene mutations, chromosomal change, and genetic instability. This leads to loss of normal cell and tissue homeostasis, and development of malignancy. (L1837) |
1999 |
Acyl-CoA-binding protein | Lead is known to bind ACBP, which is responsible for the regulation of various processes such as acyl-CoA metabolism, GABA-A/benzodiazepine receptor modulation, steroidogenesis, intestinal cholecystokinin release, and insulin secretion. (A21) |
9817074 |
Glutamate receptor ionotropic, NMDA 1 Glutamate receptor ionotropic, NMDA 2B Glutamate receptor ionotropic, NMDA 2A Glutamate receptor ionotropic, NMDA 3B Glutamate receptor ionotropic, NMDA 2C Glutamate receptor ionotropic, NMDA 2D Glutamate receptor ionotropic, NMDA 3A |
Lead exhibits competitive inhibition at the NMDA receptor, affecting neurotransmitter release. (A22) |
10454514 |
Calmodulin | Lead has been shown to competitively inhibit calcium's binding of calmodulin, interfering with neurotransmitter release. Lead binding of calmodulin causes improper activation, altering proper functioning of cAMP messenger pathways. (A20) |
14624473 |
Thymosin beta-4 | Lead has been shown to bind thymosin beta-4, which functions in the modulation of cytoskeletion, stimulation of CaM-dependent kinases, and GABA-A receptor complex function. It is also an immunotransmitter. (A21) |
9817074 |
Ferrochelatase, mitochondrial | Lead inhibition of ferrochelatase prevents the biosynthesis of heme, which is a necesssary cofactor of hemoglobin. (L21) |
|
Protein kinase C alpha type Protein kinase C beta type Protein kinase C gamma type Protein kinase C delta type Protein kinase C iota type Protein kinase C epsilon type Protein kinase C eta type Protein kinase C theta type Protein kinase C zeta type |
Lead exhibits competitive inhibition with calcium at protein kinase C, which impairs brain microvascular formation and function, as well as alters the blood-brain barrier. (L136) |
2007 |