1. Metals and Biology Flashcards
Metal toxicity: high charge density
- metals with high charge:radius
- bind tightly to proteins and DNA, interfere with activity
- e.g. Al3+ and neutrodegeneration
Metal toxicity: heavy-metal toxins
- soft acids
- interfere with protein structure and function, by binding to cysteines in protein active sites
- e.g. Hg2+, Pt2+, Pb2+
How does form of exposure affect form of metal toxicity?
Elemental Hg - ingestion and injection are not toxic, inhalation is toxic and absorbed by lungs
Inorganic Hg - Hg2+ salts more toxic than Hg+ due to higher solubility and forms dangerous compounds
Organic (CH3HgCl) - lipophilic and hydrophilic, can cross blood-brain barrier and placental membrane
Metal toxicity: mimicking essential metals
- metal ions with similar size and preferred ligand sets
- Pb2+ mimics Ca (can displace) and cause deficiencies
- Cd2+ mimics Zn2+ and Ca2+ (cannot pass into CNS) -> cause brittle bones, deformed skeleton, kidney failure
Metal toxicity: carcinogenic metals
- chromate ion is isoelectric and isostructural to sulfate, hydrogen phosphate
- Cr(III) binds to DNA, causes mutations and cancer
Properties of chelation agent
- high selectivity for metal (metal size, donor group, coordination number)
- stable complex (tight binding, polydentate ligand)
- can be excreted (solubility, not lipophilicity)
Effects of too much/too little copper and treatment
Too much: toxic from soft Cu(I) binding to proteins, redox -> forms free radicals, Menkes disease (weak muscle tone, mental retardation, seizures)
Too less: essential copper-containing enzymes lose activity, Wilson’s disease (psychiatric problems)
Treatment: copper chelating agents, copper histadine complexes
Effects of too much/too little iron and treatment
Too much: toxic from redox (free radicals)
Too less: poor oxygenation of essential organs, fatigue (anaemia)
Treatment: complex agents with high affinity for Fe called siderophores (chelation agents), blood-letting
Silver antimicrobial agents
- prevents growth of bacteria and yeast on damaged skin
- silver sulfadiazine (metal toxic and binds to SH in proteins and enzymes in bacteria)
Mercury antimicrobial agents
- antiseptic, in vaccines, causes bacteria to undergo autolysis
- metal toxic and binds to enzymes in bacteria
Pt anticancer agents
- cisplatin - anticancer, prevents replication
- metal controls geometry and binds to DNA
- Cl labile -> exchanges with OH which is readily lost, giving two sites to attack DNA
Limitations of cisplatin
Resistance
- cancer cell could mutate
- cancer cell could change to survive in high Cl- environments
Toxicity
- renal toxicity (kidneys can be destroyed by Pt)
- nausea, vomiting
- neurotoxicity (hearing and balance loss)
