The term “vitamin B12 ” is used as a generic descriptor for the cobalamins—those corrinoids (cobalt-containing compounds possessing the corrin ring) having the biological activity of the vitamin (Figure 1). Some corrinoids that are growth factors for microorganisms not only have no vitamin B12 activity, but may also be antimetabolites of the vitamin. Although it is synthesized exclusively by microorganisms, for practical purposes vitamin B12 is found only in foods of animal origin, there being no plant sources of this vitamin. This means that strict vegetarians (vegans) are at risk of developing B12 deficiency. The small amounts of the vitamin formed by bacteria on the surface of fruits may be adequate to meet requirements, but preparations of vitamin B12 made by bacterial fermentation are available.

Fig1. Vitamin B12 .Four coordination sites on the central cobalt atom are chelated by the nitrogen atoms of the corrin ring, and one by the nitrogen of the dimethylbenzimidazole nucleotide. The sixth coordination site may be occupied by CN− (cyanocobalamin), OH− (hydroxocobalamin), H2 O (aquocobalamin, —CH3 (methyl cobalamin), or 5′-deoxyadenosine (adenosylcobalamin).

Vitamin B12 Absorption Requires Two Binding Proteins

 Vitamin B12 is absorbed bound to intrinsic factor, a small glycoprotein secreted by the parietal cells of the gastric mucosa. Gastric acid and pepsin release the vitamin from protein binding in food and make it available to bind to cobalophilin, a binding protein secreted in the saliva. In the duodenum, cobalophilin is hydrolyzed, releasing the vitamin for binding to intrinsic factor. Pancreatic insufficiency can therefore be a factor in the development of vitamin B12 deficiency, resulting in the excretion of cobalophilin-bound vitamin B12 . Intrinsic factor binds only the active vitamin B12 vitamers and not other corrinoids. Vitamin B12 is absorbed from the distal third of the ileum via receptors that bind the intrinsic factor–vitamin B12 complex, but not free intrinsic factor or free vitamin. There is considerable enterohepatic circulation of vitamin B12 , with excretion in the bile, then reabsorption after binding to intrinsic factor in the ileum.

There Are Two Vitamin B12–Dependent Enzymes

Methylmalonyl-CoA mutase, and methionine synthase (Figure 2) are vitamin B12–dependent enzymes. Methyl malonyl-CoA is formed as an intermediate in the catabolism of valine as well as by the carboxylation of propionyl-CoA arising from the catabolism of isoleucine, cholesterol, and fatty acids with an odd number of carbon atoms, or propionate, a major product of microbial fermentation ruminants. Methylmalonyl CoA undergoes a vitamin B12–dependent rearrangement to succinyl-CoA, catalyzed by methylmalonyl-CoA mutase. The activity of this enzyme is greatly reduced in vitamin B12 deficiency, leading to an accumulation of methylmalonyl-CoA and urinary excretion of methylmalonic acid, which provides a means of assessing vitamin B12 nutritional status.

Fig2. Homocysteine and the folate trap. Vitamin B12 deficiency leads to impairment of methionine synthase, resulting in accumulation of homocysteine and trapping folate as methyltetrahydrofolate.

Vitamin B12 Deficiency Causes Pernicious Anemia

Pernicious anemia arises when vitamin B12 deficiency impairs the metabolism of folic acid, leading to functional folate deficiency that disturbs erythropoiesis, causing immature precursors of erythrocytes to be released into the circulation (megaloblastic anemia). The most common cause of pernicious anemia is failure of the absorption of vitamin B12 rather than dietary deficiency. This can be the result of failure of intrinsic factor secretion caused by autoimmune disease affecting parietal cells or from production of anti-intrinsic fac tor antibodies. There is irreversible degeneration of the spinal cord in pernicious anemia, as a result of failure of methylation of one arginine residue in myelin basic protein. This is the result of methionine deficiency in the central nervous system, rather than secondary folate deficiency.

اخر الاخبار

اخبار العتبة العباسية المقدسة

تعرف إلى منافذ جمع التبرعات لدعم الشعبين الإيراني واللبناني

قسم الشؤون الدينية يستأنف دوراته الفقهية لمنتسبي العتبة العباسية المقدسة

قسم الشؤون الفكرية يعلن أسماء الفائزين في مسابقة (فنروى) الثقافية

سماحة السيد الصافي: للشعب العراقي علاقة مميزة مع المرجعية الدينية العليا وتفاعل إيجابي مع توجيهاتها الإنسانية

المزيد

الآخبار الصحية

مؤشرات يومية بسيطة تتفوق على الفحوصات الطبية في التنبؤ بالعمر المتوقع !

كيف تؤثر العناية بالأسنان على صحة الكبد؟

نتائج حديثة مقلقة حول القنب والتبغ

الشوكولاتة وحدها لا تسبب السكري.. عوامل أخرى مؤثرة

المزيد

الآخبار التكنلوجية

بسبب الحروب: أزمة الألمنيوم وتأثيرها على صناعة السيارات

انقطاع مؤقت للاتصال مع طاقم "أرتميس 2" خلال الرحلة إلى القمر

واشنطن تضغط على حلفاءها لتعزيز سلاسل توريد الحوسبة الكمومية

لماذا يصر دونالد ترامب على العودة إلى القمر؟

المزيد

مواضيع ذات صلة

Knowledge of Enzyme Kinetics, Mechanism, and Inhibition Aids Drug Development

Multiple Factors Affect the Rates of Enzyme-Catalyzed Reactions

The Rates of Reactions are Determined by Their Activation Energy

Ribozymes: Artifacts from the RNA World

The Catalytic Activity of Enzymes Facilitates Their Detection

Chymotrypsin & Fructose-2,6-Bisphosphatase Illustrate Covalent Catalysis

Iron Metabolism

Biochemistry and Biosynthesis of Adrenal Steroids and Testosterone Steroids

Enzymes Employ Multiple Mechanistic Strategies to Facilitate Catalysis

The Oxygen Dissociation Curves for Myoglobin & Hemoglobin Suit Their Physiologic Roles

Heme & Ferrous Iron Confer the Ability to Store & Transport Oxygen

Control of Heme Biosynthesis