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• Route 1: Lead is known to have a strong affinity towards sulfur. In human body, sulfur exists in the form of thiols. So, lead tries to bind with thiol group¹ leading to major implications.

• Route 2: Lead is able to produce free radical and reactive oxygen species (ROS) via Fenton-Haver-Weiss pathway² possible by stimulating NADPH oxidases or by competing for the metal binding site of an enzyme/protein (Route 3) or by attacking the thiols moiety of protein (Route 1). The mechanism is below:

  It causes a destructive behavior known as oxidative stress. One of the major implication of oxidative stress is lead-induced hypertension and cardiovascular disease. The mechanism is provided in below reference³

• Route 3: Lead is known to mimic calcium because they share similar properties (In its +2 cationic form, lead has a radius of 132 pm while the calcium cation has a radius of 106 pm. In their elemental forms, lead has a radius of 175 pm and calcium has a radius of 197 pm). And that is the reason, lead compete with calcium and substitutes calcium from cells, tissues and enzymatic sites. One of the major effect is on calmodulin which is a calcium binding protein and lead will try to replace calcium inhibiting phosphorylation of brain membranes⁴.

• Route 1: Lead is known to have a strong affinity towards sulfur. In human body, sulfur exists in the form of thiols. So, lead tries to bind with thiol group¹ leading to major implications.

• Route 2: Lead is able to produce free radical and reactive oxygen species (ROS) via Fenton-Haver-Weiss pathway² possible by stimulating NADPH oxidases or by competing for the metal binding site of an enzyme/protein (Route 3) or by attacking the thiols moiety of protein (Route 1). The mechanism is below:

  It causes a destructive behavior known as oxidative stress. One of the major implication of oxidative stress is lead-induced hypertension and cardiovascular diseases³

• Route 3: Lead is known to mimic calcium because they share similar properties (In its +2 cationic form, lead has a radius of 132 pm while the calcium cation has a radius of 106 pm. In their elemental forms, lead has a radius of 175 pm and calcium has a radius of 197 pm). And that is the reason, lead compete with calcium and substitutes calcium from cells, tissues and enzymatic sites. One of the major effect is on calmodulin which is a calcium binding protein and lead will try to replace calcium inhibiting phosphorylation of brain membranes⁴.

• Route 1: Lead is known to have a strong affinity towards sulfur. In human body, sulfur exists in the form of thiols. So, lead tries to bind with thiol group¹ leading to major implications.

• Route 2: Lead is able to produce free radical and reactive oxygen species (ROS) via Fenton-Haver-Weiss pathway² possible by stimulating NADPH oxidases or by competing for the metal binding site of an enzyme/protein (Route 3) or by attacking the thiols moiety of protein (Route 1). The mechanism is below:

  It causes a destructive behavior known as oxidative stress. One of the major implication of oxidative stress is lead-induced hypertension and cardiovascular disease. The mechanism is provided in below reference³

• Route 3: Lead is known to compete with calcium and substitutes calcium from cells and tissues. The major effect is on calmodulin which is a calcium binding protein and lead will try to replace calcium inhibiting phosphorylation of brain membranes⁴.

1. Magyar JS, Weng TC, Stern CM, Dye DF, Rous BW, Payne JC, Bridgewater BM, Mijovilovich A, Parkin G, Zaleski JM, Penner-Hahn JE, Godwin HA. Reexamination of lead(II) coordination preferences in sulfur-rich sites: implications for a critical mechanism of lead poisoning. J Am Chem Soc. 2005 127(26):9495-505. doi: 10.1021/ja0424530
2. Kehrer JP. The Haber-Weiss reaction and mechanisms of toxicity. Toxicology. 2000 Aug 14;149(1):43-50. doi: 10.1016/s0300-483x(00)00231-6
3. Mechanisms of lead-induced hypertension and cardiovascular disease, Nosratola D. Vaziri, American Journal of Physiology-Heart and Circulatory Physiology 2008 295:2, H454-H465, DOI: 10.1152/ajpheart.00158.2008
4. Habermann E, Crowell K, Janicki P. Lead and other metals can substitute for Ca2+ in calmodulin. Arch Toxicol. 1983 Sep;54(1):61-70. doi: 10.1007/BF00277816
5. FHW pathway mechanism image source: Trace Metals in the Environment by Daisy Joseph, 2023

• Route 1: Lead is known to have a strong affinity towards sulfur. In human body, sulfur exists in the form of thiols. So, lead tries to bind with thiol group¹ leading to major implications.

• Route 2: Lead is able to produce free radical and reactive oxygen species (ROS) via Fenton-Haver-Weiss pathway² possible by stimulating NADPH oxidases or by competing for the metal binding site of an enzyme/protein (Route 3) or by attacking the thiols moiety of protein (Route 1). The mechanism is below:

  It causes a destructive behavior known as oxidative stress. One of the major implication of oxidative stress is lead-induced hypertension and cardiovascular disease. The mechanism is provided in below reference³

• Route 3: Lead is known to mimic calcium because they share similar properties (In its +2 cationic form, lead has a radius of 132 pm while the calcium cation has a radius of 106 pm. In their elemental forms, lead has a radius of 175 pm and calcium has a radius of 197 pm). And that is the reason, lead compete with calcium and substitutes calcium from cells, tissues and enzymatic sites. One of the major effect is on calmodulin which is a calcium binding protein and lead will try to replace calcium inhibiting phosphorylation of brain membranes⁴.

1. Magyar JS, Weng TC, Stern CM, Dye DF, Rous BW, Payne JC, Bridgewater BM, Mijovilovich A, Parkin G, Zaleski JM, Penner-Hahn JE, Godwin HA. Reexamination of lead(II) coordination preferences in sulfur-rich sites: implications for a critical mechanism of lead poisoning. J Am Chem Soc. 2005 127(26):9495-505. doi: 10.1021/ja0424530
2. Kehrer JP. The Haber-Weiss reaction and mechanisms of toxicity. Toxicology. 2000 Aug 14;149(1):43-50. doi: 10.1016/s0300-483x(00)00231-6
3. Mechanisms of lead-induced hypertension and cardiovascular disease, Nosratola D. Vaziri, American Journal of Physiology-Heart and Circulatory Physiology 2008 295:2, H454-H465, DOI: 10.1152/ajpheart.00158.2008
4. Habermann E, Crowell K, Janicki P. Lead and other metals can substitute for Ca2+ in calmodulin. Arch Toxicol. 1983 Sep;54(1):61-70. doi: 10.1007/BF00277816
5. https://sites.tufts.edu/leadpoisoning/pathways/lead-and-calcium/
6. FHW pathway mechanism image source: Trace Metals in the Environment by Daisy Joseph, 2023

• Route 1: Lead is known to have a strong affinity towards sulfur. In human body, sulfur exists in the form of thiols. So, lead tries to bind with thiol group¹ leading to major implications.
• Route 2: Lead is able to produce free radical and reactive oxygen species (ROS) via Fenton-Haver-Weiss pathway². It causes a destructive behavior known as oxidative stress. One of the major implication of oxidative stress is lead-induced hypertension and cardiovascular disease. The mechanism is provided in below reference³
• Route 3: Lead is known to compete with calcium and substitutes calcium from cells and tissues. The major effect is on calmodulin which is a calcium binding protein and lead will try to replace calcium inhibiting phosphorylation of brain membranes⁴.

Notes and References:

1. Magyar JS, Weng TC, Stern CM, Dye DF, Rous BW, Payne JC, Bridgewater BM, Mijovilovich A, Parkin G, Zaleski JM, Penner-Hahn JE, Godwin HA. Reexamination of lead(II) coordination preferences in sulfur-rich sites: implications for a critical mechanism of lead poisoning. J Am Chem Soc. 2005 127(26):9495-505. doi: 10.1021/ja0424530
2. Kehrer JP. The Haber-Weiss reaction and mechanisms of toxicity. Toxicology. 2000 Aug 14;149(1):43-50. doi: 10.1016/s0300-483x(00)00231-6
3. Mechanisms of lead-induced hypertension and cardiovascular disease, Nosratola D. Vaziri, American Journal of Physiology-Heart and Circulatory Physiology 2008 295:2, H454-H465, DOI: 10.1152/ajpheart.00158.2008
4. Habermann E, Crowell K, Janicki P. Lead and other metals can substitute for Ca2+ in calmodulin. Arch Toxicol. 1983 Sep;54(1):61-70. doi: 10.1007/BF00277816

• Route 1: Lead is known to have a strong affinity towards sulfur. In human body, sulfur exists in the form of thiols. So, lead tries to bind with thiol group¹ leading to major implications.

• Route 2: Lead is able to produce free radical and reactive oxygen species (ROS) via Fenton-Haver-Weiss pathway² possible by stimulating NADPH oxidases or by competing for the metal binding site of an enzyme/protein (Route 3) or by attacking the thiols moiety of protein (Route 1). The mechanism is below:

  It causes a destructive behavior known as oxidative stress. One of the major implication of oxidative stress is lead-induced hypertension and cardiovascular disease. The mechanism is provided in below reference³

• Route 3: Lead is known to compete with calcium and substitutes calcium from cells and tissues. The major effect is on calmodulin which is a calcium binding protein and lead will try to replace calcium inhibiting phosphorylation of brain membranes⁴.

References:

1. Magyar JS, Weng TC, Stern CM, Dye DF, Rous BW, Payne JC, Bridgewater BM, Mijovilovich A, Parkin G, Zaleski JM, Penner-Hahn JE, Godwin HA. Reexamination of lead(II) coordination preferences in sulfur-rich sites: implications for a critical mechanism of lead poisoning. J Am Chem Soc. 2005 127(26):9495-505. doi: 10.1021/ja0424530
2. Kehrer JP. The Haber-Weiss reaction and mechanisms of toxicity. Toxicology. 2000 Aug 14;149(1):43-50. doi: 10.1016/s0300-483x(00)00231-6
3. Mechanisms of lead-induced hypertension and cardiovascular disease, Nosratola D. Vaziri, American Journal of Physiology-Heart and Circulatory Physiology 2008 295:2, H454-H465, DOI: 10.1152/ajpheart.00158.2008
4. Habermann E, Crowell K, Janicki P. Lead and other metals can substitute for Ca2+ in calmodulin. Arch Toxicol. 1983 Sep;54(1):61-70. doi: 10.1007/BF00277816
5. FHW pathway mechanism image source: Trace Metals in the Environment by Daisy Joseph, 2023