미네랄의 독성 기작

단백질 ≫ 역할 ≫ 효소

미네랄의 독성 기작

Mineral 이야기
- 미네랄의 역할 :  지성규박사
- 미네랄의 종류와 특성
- 미네랄 권장량
- 식물의 미네랄
- 금속 단백질 : 효소와 미네랄
- 효소를 방해하는 중금속

자료출처 :
 


 

비소
The toxicity of the particular arsenic compound depends on its valence state which may be zero-, tri- or penta-valent, and the whether the compound is organic or inorganic, as well as on physical aspects such as absorption and elimination. Generally inorganic compounds are more toxic than organic compounds and trivalent compounds are more toxic than penta- or zero-valent compounds. Organic compounds are estimated to be 50-100 times more toxic
After absorbtion of inorg anic arsenic, the compound accumulates in the liver, spleen, kidneys, lungs and gastrointestinal tract. It is then rapidly cleared from these tissues but it leaves a residue in keratin-rich tissues such as skin, hair and nails. Ingested inorganic salts a re well absorbed if they are soluble, and very soluble salts may also be able to enter the body through the skin and by inhalation. The lethal dose of inorganic arsenic is estimated to be between 120 and 200 mg
Some arsenic compounds notably arsenite (pentavalent, inorganic) are metabolised in the liver and this leads to the formation of compounds which are less toxic. Methyl groups are added to the arsenite which forms methylarsenic acid and dimethylarsenic acid. However this biomethylatation process can easily become saturated and this can lead to the excess inorganic arsenic being deposited in the soft tissues
Arsenic compounds are directly toxic to body systems. Particularly in the trivalent form, they are able to bind to sulphydryl groups of enzymes in the pyruvate dehydrogenase system. They are also able to bind to enzymes in the Kreb's (Tricarboxylic acid) cycle and they therefore can interfere with oxidative phosphorylation in cells. In the pentavalent form, they can also exert their toxicity by competitively substituting their ions for the body's phosphate ions. This can lead to the breaking down by hydrolysis of high energy bonds in compounds such as ATP. Organic arsenic compounds can also induce sensitisation reactions

카드뮴
Humans have a daily intake of cadmium from ingestion and inhalation which is around 20 to 40 µg per day, but only 5 to 10% of this is absorbed 8. After absorbtion, cadmium is transported in the blood bound to albumin. It is taken up by the liver, and, due to its similarity to zinc, causes this organ to induce the synthesis of the protein metallotheionin (see Introduction, metallotheionin), to which it binds. The cadmium-metallotheionin complex then becomes transported to the kidneys, and it is filtered at the glomerulus, but is reabsorbed at the proximal tubule 1, 8. Within the renal tubular cells, the cadmium-MT complex becomes degraded by digestive enzymes, which releases the cadmium. Renal tubular cells deal with the release of this toxic substance by synthesising MT to neutralise it, but eventually the kidneys loose their synthetic capacity for MT. At this point, the cadmium has accumulated to a high level in the renal tubular cells, and irreversible cell damage occurs 1, 12. As can be seen above, the renal cells do not have an effective elimination pathway for the cadmium complex, which means that the half life in the kidney is between 15 and 30 years
The toxic effects of cadmium are due to its inhibition of various enzyme systems. Like similar heavy metals, it is able to inactivate enzymes containing sulphydryl groups and it can also produce uncoupling of oxidative phosphorylation in mitochondria 4. Cadmium may also compete with other metals such as zinc and selenium for inclusion into metallo-enzymes and it may compete with calcium for binding sites on regulatory proteins such as calmodulin

납
Elemental lead and inorganic lead compounds are absorbed by ingestion or inhalation, but organic lead compounds e.g. tetraethyl lead may also be absorbed by skin contact. Organic lead compounds are the most toxic. Absorption of lead from the lungs is very efficient, especially is the particles are less than 1 micrometre in diameter, as may happen for example with fumes from burning lead paint. Gastrointestinal absorption of lead varies with the age of the individual; children absorb around 50% of what they ingest, but adults only absorb 10-20% of what they ingest
Lead is very similar chemically to calcium, so once in the body, it is handled as if it were calcium 5. The flow diagram below shows what happens in the body after an intake of lead:

(Diagram adapted from text in 4, 5, 8 and 12)

Lead in the blood has a half-life of around 25 days and in tissue its half-life is about 40 days 8, 13. Due to this, blood lead levels are not very useful as an indicator of how much lead exposure an individual has undergone, as they only show recent exposure 12, 13. However, in non-labile bone lead has a half-life of 25 years or more, and it is possible to estimate past exposure to lead by x-ray 8. Lead is excreted from the body mainly in the urine but also in the faeces, and small amounts also appear in hair, nails, sweat, saliva and breast milk
Lead is toxic as it has an affinity for cell membranes and mitochondria, and interferes with mitochondrial oxidative phosphorylation. It also affects sodium, potassium and calcium ATP-ase pumps which maintain the cells’ concentration gradients of these ions. The activity of calcium-dependent intracellular messengers, and in the brain the enzyme protein kinase C are also impaired. Lead also stimulates the formation of inclusion bodies in cells that may translocate the metal into the cell’s nuclei and alter gene expression

수은
Mercury exerts its toxicity by the metal or its ions binding to sulphydryl groups in the body. These groups may be part of some enzymes, and hence mercury and its compounds are potent inhibitors of some enzymes 4, 12, 13, 15. Mercury also blocks the transport of potassium into cells and also blocks the transport of sugars. These effects are due to the binding of mercury to the S-H groups in or on the cell membrane. Once inside the cell, the metal may be sequestered in an inactive combination, or it may react with enzymes or other compounds to elicit other toxic effects
Once inside the body, mercury undergoes a process called biotransformation. The carbon-mercury bond in organic compounds is broken, which in alkyl mercury compounds is known as demethylation, but methylation also occurs. Intakes of elemental and divalent mercury cause the interconversion of the forms to each other 1, 4. An intake of elemental mercury vapour is absorbed through the lungs then is oxidised in red blood cells to Hg2+. It is also taken up by the brain and the foetus and is also metabolised to Hg2+ in these tissues, and the mercury then becomes trapped in these sites as it is ionised. Organic mercury is able to distribute to the CNS, where it is oxidised (alkyl mercury compounds are demethylated) to Hg2+ and leads to neurological damage 12. Exposure of the body to mercury in any of its forms stimulates the kidney to produce metallothionein, a metal-binding protein that affords partial protection against mercury toxicity.
Elemental mercury is not well absorbed by the GI tract, but its vapour is well absorbed by the lungs. Its half life in the blood is around 60 days, but as mentioned above, it is fat soluble so is able to cross the blood-brain barrier and the placenta. In these tissues and in the kidneys it may be oxidised by catalase and hydrogen peroxide into mercuric chloride, and may be retained by the kidney and brain for years.
Inorganic mercury can be absorbed through the gastro-intestinal tract but also through the skin 7, 8. Because large overdoses damage the GI mucosa, the loss of this barrier further enhances the absorption through this route. Once it has been absorbed, it breaks down to metallic and mercuric mercury, but relatively little crosses the blood brain barrier. Its half life in the blood is around 40 days but it may be retained in the kidneys as mercuric mercury.
Organic mercury compounds, particularly methyl mercury, can evaporate and undergo pulmonary absorbtion, and are also well absorbed by ingestion. However, very little of these compounds is absorbed through the skin. As it is lipid soluble, once it enters the body it crosses the blood-brain barrier and the placenta and appears in breast milk. It also concentrates in the kidneys and the CNS. The half life of organic mercury is around 70 days in the body.

탈륨
Thallium can be absorbed from the skin as well as by inhalation and ingestion 8. When thallium enters the body, in the first few hours it distributes throughout the vascular space. After about 48 hours in the body, it starts entering the CNS and other tissues. As thallium is a heavy metal, its method of action is to bind to sulphydryl groups in the body, which upsets many biochemical processes. It resembles potassium in size and charge, so it has a wide distribution volume. The body tries to excrete the thallium by secreting about 2/3rds of it into the intestine (much of which is reabsorbed), and the remaining 1/3rd is excreted in the urine 1. Thallium has a half life in the body of up to 30 days, but this may be reduced to as little as 2 days with treatment. (see ‘treatment’ section below).