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KIMIA BIOANORGANIK KOBALT 1934
Anti pernicious anemia faktor berhasil diisolasi dan dikristalkan dinamakan dengan Vitamin B12
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Strukturnya dapat ditentukan dengan teknik X ray
Vitamin B12 B12 merupakan kompleks makromolekul yang terdiri dari ligan corrin dengan atom pusat Cobalt (III) Rumus Molekulnya sbb: C61-64H84-90N14O13-14PCo Ligan corrin merupakan modifikasi dari ligan porpirin
Kerangka Struktur dari Ligan Corrin dan Ligan porpirin
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Struktur dari Vitamin B12
Sianokobaltamin (Vitamin B12)
Fungsi: Sebagai koenzim yang berhubungan dengan vitamin B12 Terikat pada cincin corrin, yang terdiri dari empat komponen: 1. Satu atom kobalt (III) 2. Ligan makrosiklik cincin corrin 3. Bagian kompleks organik yang terdiri atas gugus fosfat, gula dan basa organik. 4. Ligan R yang terkoordinasi pada atom Cobalt R
CN (Vitamin B12 = sianokobaltamin)
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Ligan sianida ditemukan selama prosedur isolasi, dan tidak ditemui dalam bentuk aktif vitamin
R
bisa juga H2O 5-deoksiadenosil metil hidroksi Metanogen merupakan tipe bakteri primitif : archeobacteria Berperan dalam memproduksi gas metana yang dibantu oleh katalis nikel (dalam kompleks nickel corrinoid (F430)) dan cobalt (terikat dalam bentuk vitamin B12) 4H2 + CO2
Nikel corrinoid
CH4 + 2H2O
Nikel yang terikat dengan ligan corrin, seperti halnya cobalt
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Kobaltamina dapat direduksi dalam larutan netral atau alkali menghasilkan Co (II) dan Co (I) Reduksi dua elektron oleh NADH dan flavin adenin dinukleotida (FAD) Kompleks Co (II) B12r Kompleks Co (I)
B12s
B12s adalah zat pereduksi kuat, mendekomposisi air menghasilkan hidrogen dan B12r, berlangsung secara in vivo oleh ferredoksin tereduksi Kompleks kobalt (I) bereaksi dengan alkil halida, melalui reaksi adisi oksidatif. [B12(CoI)] + CH3I
[B12(CoIII)-CH3]+ + I-
Vitamin B12 yang melibatkan bentuk tereduksi Co+1 mempunyai dua fungsi: 1.
Reduksi senyawa organik
2.
Terlibat dalam pengikatan gugus metil dari N5metiltetrahidrofolat (CH3-THF)
Vitamin B12 adalah satu-satunya vitamin mengandung logam, esensial bagi hewan dan manusia, tidak terdapat pada tumbuhan dan tidak bisa disintesis oleh hewan, tapi bisa disintesis oleh bakteri.
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Metaloenzim Kobalt 1. Enzim mutase, mutasi hidrogen dengan beberapa kelompok senyawa karbon yang berdekatan. Contoh: a. Glutamat mutase b. Metilmalonil CoA mutase c. Ornitin mutase d. L-β-lisin mutase e. α-metilenglutarat mutase Dapat juga diikuti dengan eliminasi air atau amonia a. Dioldehidrase b. Gliserol dehidrase c. Etanolamin amonia lyase
2. Ribonukleotida reduktase Ribosa direduksi menjadi deoksiribosa
3. Transfer group metil a. Metionin sintetase b. Metan sintetase c. Asetat sintetase
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Vitamin B12 bereaksi dengan ATP, reaksi alkilasi akan berperan dengan pembentukan langsung ikatan karbonkobalt, antara adenosin dan kobalt, senyawa tersebut dengan Koenzim B12
Pernicious Anemia :
Gejala penyakit ketidakmampuan menyerap vitamin B12 melalui dinding usus, ditandai dengan naiknya ekskresi dari asam metil malonat.
Anaemia due to vitamin B12 deficiency (pernicious anaemia) What is anaemia? Anaemia is a deficiency of red blood cells that can lead to a mild lack of oxygen-carrying ability causing unusual tiredness. Red blood cells are manufactured in the bone marrow and have a life expectancy of approximately four months. Anaemia occurs either through the reduced production of red blood cells or an increased loss of red blood cells. Meat, fish and cheese are all good sources of vitamin B12.
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What are red blood cells? Red blood cells are the cells that circulate in the blood plasma (fluid). Through its pumping action, the heart propels the blood around the body through the arteries. The red blood cells obtain oxygen in the lungs and carry it to all the body's cells. The cells use the oxygen to fuel the combustion (burning) of sugar and fat which produces the body's energy. When the muscles are used, carbon dioxide is created as a waste product. It binds itself to the red blood cells that have delivered their load of oxygen. The carbon dioxide is then transported back to the lungs where it is exchanged for fresh oxygen by breathing.
Why does a vitamin B12 deficiency cause anaemia? To produce red blood cells, the body needs, among other things, iron, vitamin B12 and folic acid (one of the B group of vitamins). If one or more of these ingredients is lacking, anaemia will develop. Vitamin B12 is also essential for the nervous system, which is why a deficiency can also cause inflammation of the nerves (neuritis) and dementia (mental deterioration). Vitamin B12 deficiency is frequently caused either by the inability of the small bowel to absorb vitamin B12, or by a lack of food containing vitamin B12. It frequently occurs in elderly people although it may also be present in the young, particularly women.
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What are the causes of vitamin B12 deficiency? A vegetarian or vegan diet can cause vitamin B12 deficiency because vitamin B12 is only found in foods of animal origin, such as meat, liver, fish, eggs and milk. In the UK, by far the most common cause of vitamin B12 deficiency is a lack of 'intrinsic factor', a substance which is produced in the stomach and enables the body to absorb vitamin B12 from the diet.
Causes for a reduced production of intrinsic factor are: the formation of antibodies against the cells producing intrinsic factor. The cells then die and B12 deficiency and anaemia (also called pernicious anaemia) develop. stomach cancer and ulcers can take up so much room in the stomach that there are too few cells remaining producing intrinsic factor. diseases of the small intestine, fish tapeworm and the aftereffects of surgery to the small intestine can all mean that the surface of the small intestine is too small to obtain B12 and intrinsic factor effectively.
What are the symptoms of anaemia due to vitamin B12 deficiency? The first symptoms will be unusual tiredness, difficulty in breathing and dizziness. Further symptoms specific to vitamin B12 deficiency are: a red, irritated and possibly shiny, tongue.
a reduced sense of taste. altered or reduced sense of touch. reduced sense of vibration (an inability to feel the vibrations of a tuning fork). some people with vitamin B12 deficiency will experience symptoms in their nervous system first. headache. psychological symptoms. pains in the legs (intermittent claudication), difficulties with walking and coordination will gradually occur together with muscle spasm paralysis. a less sensitive sense of touch. shortness of breath, palpitation and chest pains (angina). with pernicious anaemia there is an increased danger of developing cancer of the stomach.
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What can be done to avoid vitamin B12 deficiency? Eat a varied diet. Good sources of vitamin B12 are liver, fish and eggs.
Because vitamin B12 is only found in food of animal origin, strict vegetarians should take vitamin B12 supplements to avoid deficiency. If a family member also suffers from pernicious anaemia extra care should be taken to prevent deficiency. Anyone who has undergone surgery in their small intestine or stomach should pay attention to any of the symptoms mentioned above.
How does the doctor diagnose vitamin B12 deficiency and anaemia? First the doctor must be sure that the patient is suffering from anaemia. A blood sample will be taken and an analysis of the red blood cells will usually be included. In cases of vitamin B12 deficiency, the red blood cells will be the usual colour but larger than normal. If the blood test shows a low vitamin B12 count, it must be established whether it is pernicious anaemia or if there is some other cause. The patient will be given the Schilling test to measure the body's ability to absorb vitamin B12 from the bowel. This will show whether the anaemia is caused by a lack of intrinsic factor. Blood tests will also show if the patient has any antibodies to intrinsic factor or to other organs in the body.
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What can the doctor do?
Examine the patient and prescribe treatment to deal with the causes of the disease. Prescribe vitamin B12 injections. These are given every three months and will usually be continued throughout the patient's life. They have few side effects.
Prognosis By eliminating the cause and taking the necessary vitamins by supplement or injection, there will be a complete recovery.
However, even if the pernicious anaemia is treated, there is a slightly increased risk of cancer of the stomach and if the treatment is started too late there is a risk of permanent damage to the nervous system.
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