Hydroxocobalamin
Encyclopedia
Hydroxocobalamin is a natural form, or vitamer
, of vitamin B12
, a basic member of the cobalamin family of compounds. Hydroxocobalamin is the form of vitamin B12 produced by many bacteria which are used to produce the vitamin commercially. Like other forms of vitamin B12, hydroxocobalamin has an intense red color. It is not a form normally found in the human body, but is easily converted in the body to usable coenzyme forms of vitamin B12. Pharmaceutically, hydroxycobalamin is usually produced as a sterile injectable solution, and is used for treatment of the vitamin deficiency, and also (because of its afinity for cyanide ion) as a treatment for cyanide poisoning
. Experimentally, it has been tested as a scavenger of nitric oxide
.
Vitamin B12 is a term that refers to a group of compounds called cobalamins that are available in the human body in a variety of mostly interconvertible forms. Together with folic acid, cobalamins are essential cofactors required for DNA
synthesis in cells where chromosomal replication and division are occurring—most notably the bone marrow
and myeloid
cells. As a cofactor
, cobalamins are essential for two cellular reactions: (1) the mitochondrial methylmalonylcoenzyme A mutase conversion of methylmalonic acid
(MMA) to succinate, which links lipid and carbohydrate metabolism, and (2) activation of methionine synthase, which is the rate limiting step in the synthesis of methionine from homocysteine and 5-methyltetrahydrofolate.
Distribution Coefficient: 1.133 × 10-5 (octanol:acetate buffer pH 7.4) pKa: 7.65
Systematic Name: Cobinamide, Co-hydroxy-, dihydrogen phosphate (ester), inner salt, 3'- ester with (5,6-dimethyl-1-alpha-D-ribofuranosyl-1H-benzimidazole- kappaN3)
replacement therapy, usually at 100 mcg/dose. In the UK 1,000mcg (1 mg) per dose is generally used. Damage that results from vitamin B12 deficiency can be prevented with early diagnosis and adequate treatment.
For most, the standard therapy for treatment of vitamin B12 deficiency has been intramuscular (IM) injections of vitamin B12 in the form of cyanocobalamin
(CNCbl) or hydroxocobalamin (OHCbl). CNCbl is traditionally prescribed in the United States
. Outside of the United States, OHCbl is most generally used for vitamin B12 replacement therapy and is considered the “drug of choice” for vitamin B12 deficiency by the Martindale Extra Pharmacopoeia (Sweetman, 2002) and the World Health Organization
(WHO) Model List of Essential Drugs. This preference for OHCbl in many countries is due to its long retention in the body and the need for less frequent IM injections in restoring vitamin B12 (cobalamin) serum levels. Furthermore, IM administration of OHCbl is also the preferred treatment for pediatric patients with intrinsic cobalamin metabolic diseases; vitamin B12 deficient patients with tobacco amblyopia due to cyanide poisoning; and patients with pernicious anemia who have optic neuropathy (Carethers, 1988; Chisholm et al., 1967; Freeman, 1992; Markle, 1996).
In a newly-diagnosed vitamin B12-deficient patient, normally defined as when serum cobalamin (vitamin B12) levels are less than 200 pg/mL, daily IM injections of OHCbl up to 1,000 μg (1 mg) per day are given to replenish the body’s depleted cobalamin stores. In the presence of neurological symptoms, following daily treatment, injections up to weekly or biweekly are indicated for 6 months before initiating monthly IM injections. Once clinical improvement is confirmed, maintenance supplementation of B12 will generally be needed for life.
.
Hydoxyocobalamin is marketed under the trade name Cyanokit for cyanide toxicity. The standard dose is 5 gm IV infused over 15 minutes. A second 5 gm dose can be given in patients with severe toxicity. Hydroxocobalamin will bind circulating and cellular cyanide molecules to form cyanocobalamin
which is excreted in the urine.
as well as cyanide, and has been used experimentally to modifify nitric oxide
mediated inflammation. For example, a hydoxocobalamin skin creme was found to reduce chronic skin inflammation.
Hydroxycobalamin has also been used in a pilot-study treatment of migraines, as an inhibitor of nitric oxide induced vasodilation.
, cobalamins are essential cofactors required for DNA synthesis in cells where chromosomal replication and division are occurring—most notably the bone marrow
and myeloid cells. As a cofactor, cobalamins are essential for two cellular reactions: (1) the mitochondrial methylmalonyl coenzyme A mutase
conversion of methylmalonic acid
(MMA) to succinate, which links lipid and carbohydrate metabolism, and (2) activation of methionine synthase, which is the rate limiting step in the synthesis of methionine from homocysteine
and tetrahydrofolate (Katzung, 1989). Cobalamins are characterized by a porphyrin
-like corrin
nucleus that contains a single cobalt
atom bound to a benzimidazolyl nucleotide and a variable residue (R) group. The variable R group gives rise to the four most commonly known cobalamins: CNCbl
, methylcobalamin, 5-deoxyadenosylcobalamin
, and OHCbl. In the serum, OHCbl and CNCbl are believed to function as storage or transport forms of the molecule; whereas, methylcobalamin and 5¢ deoxyadenosylcobalamin are the active forms of the coenzyme required for cell growth and replication (Katzung, 1989). CNCbl is usually converted to OHCbl in the serum, whereas OHCbl is converted to either methylcobalamin or 5¢ deoxyadenosyl cobalamin. Cobalamins circulate bound to serum proteins called transcobalamins (TC) and haptocorrins
. OHCbl has a higher affinity to the TC II transport protein than CNCbl, or 5- deoxyadenosylcobalamin. From a biochemical point of view, two essential enzymatic reactions require vitamin B12 (cobalamin) (Katzung, 1989, Hardman, 2001). Intracellular
vitamin B12 is maintained in two active coenzymes, methylcobalamin and 5¢ deoxyadenosylcobalamin, which are both involved in specific enzymatic reactions. In the face of vitamin B12 deficiency, conversion of methylmalonyl-CoA to succinyl-CoA
cannot take place, which results in accumulation of methylmalonyl CoA and aberrant fatty acid synthesis. In the other enzymatic reaction, methylcobalamin supports the methionine synthase reaction, which is essential for normal metabolism of folate. The folate-cobalamin interaction is pivotal for normal synthesis of purines and pyrimidines and the transfer of the methyl group to cobalamin is essential for the adequate supply of tetrahydrofolate, the substrate for metabolic steps that require folate. In a state of vitamin B12 deficiency, the cell responds by redirecting folate metabolic pathways to supply increasing amounts of methyltetrahydrofolate
. The resulting elevated concentrations of homocysteine
and MMA are often found in patients with low serum vitamin B12 and can usually be lowered with successful vitamin B12 replacement therapy. However, elevated MMA and homocysteine concentrations may persist in patients with cobalamin concentrations between 200 to 350 pg/mL (Lindenbaum et al. 1994). Supplementation with vitamin B12 during conditions of deficiency restores the intracellular level of cobalamin and maintains a sufficient level of the two active coenzymes: methylcobalamin and deoxyadenosylcobalamin.
Vitamer
A vitamer of a particular vitamin is any of a number of chemical substances, each of which shows vitamin activity. Very commonly each "vitamin" is not a single chemical, but rather multiple chemical substances called vitamers, each of which is defined by its different biological activity.For...
, of vitamin B12
Vitamin B12
Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...
, a basic member of the cobalamin family of compounds. Hydroxocobalamin is the form of vitamin B12 produced by many bacteria which are used to produce the vitamin commercially. Like other forms of vitamin B12, hydroxocobalamin has an intense red color. It is not a form normally found in the human body, but is easily converted in the body to usable coenzyme forms of vitamin B12. Pharmaceutically, hydroxycobalamin is usually produced as a sterile injectable solution, and is used for treatment of the vitamin deficiency, and also (because of its afinity for cyanide ion) as a treatment for cyanide poisoning
Cyanide poisoning
Cyanide poisoning occurs when a living organism is exposed to a compound that produces cyanide ions when dissolved in water. Common poisonous cyanide compounds include hydrogen cyanide gas and the crystalline solids potassium cyanide and sodium cyanide...
. Experimentally, it has been tested as a scavenger of nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
.
Vitamin B12 is a term that refers to a group of compounds called cobalamins that are available in the human body in a variety of mostly interconvertible forms. Together with folic acid, cobalamins are essential cofactors required for DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
synthesis in cells where chromosomal replication and division are occurring—most notably the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
and myeloid
Myeloid
The term myeloid suggests an origin in the bone marrow or spinal cord, or a resemblance to the marrow or spinal cord.In hematopoiesis, the term "myeloid cell" is used to describe any leukocyte that is not a lymphocyte...
cells. As a cofactor
Cofactor (biochemistry)
A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....
, cobalamins are essential for two cellular reactions: (1) the mitochondrial methylmalonylcoenzyme A mutase conversion of methylmalonic acid
Methylmalonic acid
Methylmalonic acid is a dicarboxylic acid that is a C-methylated derivative of malonate.The coenzyme A linked form of methylmalonic acid, methylmalonyl-CoA, is converted into succinyl-CoA by methylmalonyl-CoA mutase, in a reaction that requires vitamin B12 as a cofactor...
(MMA) to succinate, which links lipid and carbohydrate metabolism, and (2) activation of methionine synthase, which is the rate limiting step in the synthesis of methionine from homocysteine and 5-methyltetrahydrofolate.
Chemical characteristics
Description: OHCbl acetate occurs as an odorless, dark-red orthorhombic needles. The injection formulations appear as a clear, dark-red solution.Distribution Coefficient: 1.133 × 10-5 (octanol:acetate buffer pH 7.4) pKa: 7.65
Systematic Name: Cobinamide, Co-hydroxy-, dihydrogen phosphate (ester), inner salt, 3'- ester with (5,6-dimethyl-1-alpha-D-ribofuranosyl-1H-benzimidazole- kappaN3)
Causes of deficiency
Hydroxocobalamin Injection USP, are used to rectify the following causes of vitamin B12 deficiency (list taken from the drug prescription label published by the U.S. Food and Drug Administration (FDA):- Pernicious anemia, whether uncomplicated or accompanied by nervous system involvement
- Dietary deficiency of vitamin B12 occurring in strict vegetarians and in their breastfed infants. (Isolated vitamin B12 deficiency is very rare.)
- Malabsorption of vitamin B12 resulting from structural or functional damage to the stomach where intrinsic factorIntrinsic factorIntrinsic factor also known as gastric intrinsic factor is a glycoprotein produced by the parietal cells of the stomach. It is necessary for the absorption of vitamin B12 later on in the small intestine...
is secreted or to the ileum where intrinsic factor facilitates vitamin B12 absorption (These conditions include tropical sprue and nontropical sprue [idiopathic steatorrhea, gluten-induced enteropathy]. Folate deficiency in these patients is usually more severe than vitamin B12 deficiency.) - Inadequate secretion of intrinsic factor, resulting from lesions that destroy the gastric mucosaGastric mucosaThe gastric mucosa is the mucous membrane layer of the stomach which contains the glands and the gastric pits. In men it is about 1 mm thick and its surface is smooth, soft, and velvety...
(ingestion of corrosives, extensive neoplasiaNeoplasiaNeoplasm is an abnormal mass of tissue as a result of neoplasia. Neoplasia is the abnormal proliferation of cells. The growth of neoplastic cells exceeds and is not coordinated with that of the normal tissues around it. The growth persists in the same excessive manner even after cessation of the...
, and a number of conditions associated with a variable degree of gastric atrophy, such as multiple sclerosisMultiple sclerosisMultiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
, certain endocrine disorders, iron deficiencyIron deficiency (medicine)Iron deficiency is one of the most common of the nutritional deficiencies. Iron is present in all cells in the human body, and has several vital functions...
, and subtotal gastrectomyGastrectomyA gastrectomy is a partial or full surgical removal of the stomach.-Indications:Gastrectomies are performed to treat cancer and perforations of the stomach wall....
). (Total gastrectomy always produces vitamin B12 deficiency.) - Structural lesions leading to vitamin B12 deficiency include regional ileitisIleitisIleitis is an inflammation of the ileum, a portion of the small intestine. Crohn's ileitis is a type of Crohn's disease affecting the ileum. Ileitis is caused by the bacteria Lawsonia intracellularis....
, ileal reactions, malignancies, etc. - Competition for vitamin B12 by intestinal parasites or bacteriaBacteriaBacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
- The fish tapeworm (Diphyllobothrium latum) absorbs huge quantities of vitamin B12 and infested patients often have associated gastric atrophy. The blind loop syndromeBlind loop syndromeBlind loop syndrome, also known as Stagnant loop syndrome, is a medical condition that occurs when the intestine is obstructed, slowing or stopping the progress of digested food, and thus facilitating the growth of bacteria to the point that problems in nutrient absorption occur.-Physiology:The...
may produce deficiency of vitamin B12 or folate. - Inadequate utilization of vitamin B12 (This may occur if antimetabolites for the vitamin are employed in the treatment of neoplasiaNeoplasiaNeoplasm is an abnormal mass of tissue as a result of neoplasia. Neoplasia is the abnormal proliferation of cells. The growth of neoplastic cells exceeds and is not coordinated with that of the normal tissues around it. The growth persists in the same excessive manner even after cessation of the...
.)
Vitamin B12 deficiency
Vitamin B12 compounds are used as prescription medicine (injection) for vitamin B12Vitamin B12
Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...
replacement therapy, usually at 100 mcg/dose. In the UK 1,000mcg (1 mg) per dose is generally used. Damage that results from vitamin B12 deficiency can be prevented with early diagnosis and adequate treatment.
For most, the standard therapy for treatment of vitamin B12 deficiency has been intramuscular (IM) injections of vitamin B12 in the form of cyanocobalamin
Cyanocobalamin
Cyanocobalamin is an especially common vitamer of the vitamin B12 family. It is the most famous vitamer of the family, because it is, in chemical terms, the most air-stable...
(CNCbl) or hydroxocobalamin (OHCbl). CNCbl is traditionally prescribed in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
. Outside of the United States, OHCbl is most generally used for vitamin B12 replacement therapy and is considered the “drug of choice” for vitamin B12 deficiency by the Martindale Extra Pharmacopoeia (Sweetman, 2002) and the World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
(WHO) Model List of Essential Drugs. This preference for OHCbl in many countries is due to its long retention in the body and the need for less frequent IM injections in restoring vitamin B12 (cobalamin) serum levels. Furthermore, IM administration of OHCbl is also the preferred treatment for pediatric patients with intrinsic cobalamin metabolic diseases; vitamin B12 deficient patients with tobacco amblyopia due to cyanide poisoning; and patients with pernicious anemia who have optic neuropathy (Carethers, 1988; Chisholm et al., 1967; Freeman, 1992; Markle, 1996).
In a newly-diagnosed vitamin B12-deficient patient, normally defined as when serum cobalamin (vitamin B12) levels are less than 200 pg/mL, daily IM injections of OHCbl up to 1,000 μg (1 mg) per day are given to replenish the body’s depleted cobalamin stores. In the presence of neurological symptoms, following daily treatment, injections up to weekly or biweekly are indicated for 6 months before initiating monthly IM injections. Once clinical improvement is confirmed, maintenance supplementation of B12 will generally be needed for life.
Cyanide poisoning
Hydroxocobalamin has also been used in the treatment of cyanide poisoningCyanide poisoning
Cyanide poisoning occurs when a living organism is exposed to a compound that produces cyanide ions when dissolved in water. Common poisonous cyanide compounds include hydrogen cyanide gas and the crystalline solids potassium cyanide and sodium cyanide...
.
Hydoxyocobalamin is marketed under the trade name Cyanokit for cyanide toxicity. The standard dose is 5 gm IV infused over 15 minutes. A second 5 gm dose can be given in patients with severe toxicity. Hydroxocobalamin will bind circulating and cellular cyanide molecules to form cyanocobalamin
Cyanocobalamin
Cyanocobalamin is an especially common vitamer of the vitamin B12 family. It is the most famous vitamer of the family, because it is, in chemical terms, the most air-stable...
which is excreted in the urine.
Experimental uses as nitric oxide scavenger and antiinflammatory
Hydroxycobalamin is a scavenger of nitric oxideNitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
as well as cyanide, and has been used experimentally to modifify nitric oxide
Nitric oxide
Nitric oxide, also known as nitrogen monoxide, is a diatomic molecule with chemical formula NO. It is a free radical and is an important intermediate in the chemical industry...
mediated inflammation. For example, a hydoxocobalamin skin creme was found to reduce chronic skin inflammation.
Hydroxycobalamin has also been used in a pilot-study treatment of migraines, as an inhibitor of nitric oxide induced vasodilation.
Toxicity
The literature data on the acute toxicity profile of OHCbl show that it is generally regarded as safe with local and systemic exposure. The ability of OHCbl to rapidly scavenge and detoxify cyanide by chelation has resulted in several acute animal and human studies using systemic OHCbl doses at suprapharmacological doses as high as 140 mg/kg to support its use as an intravenous (IV) treatment for cyanide exposure (Forsyth et al., 1993; Riou et al., 1993). The US FDA at the end of 2006 approved the use OHCbl as an injection for the treatment of cyanide poisoning.Vitamin B12 group
Vitamin B12 is a term that refers to a group of compounds called cobalamins that are available in the human body in a variety of mostly interconvertible forms. Together with folic acidFolic acid
Folic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...
, cobalamins are essential cofactors required for DNA synthesis in cells where chromosomal replication and division are occurring—most notably the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
and myeloid cells. As a cofactor, cobalamins are essential for two cellular reactions: (1) the mitochondrial methylmalonyl coenzyme A mutase
Methylmalonyl-CoA mutase
Methylmalonyl Coenzyme A mutase, also known as MCM is an enzyme that catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA and it is involved in key metabolic pathways...
conversion of methylmalonic acid
Methylmalonic acid
Methylmalonic acid is a dicarboxylic acid that is a C-methylated derivative of malonate.The coenzyme A linked form of methylmalonic acid, methylmalonyl-CoA, is converted into succinyl-CoA by methylmalonyl-CoA mutase, in a reaction that requires vitamin B12 as a cofactor...
(MMA) to succinate, which links lipid and carbohydrate metabolism, and (2) activation of methionine synthase, which is the rate limiting step in the synthesis of methionine from homocysteine
Homocysteine
Homocysteine is a non-protein amino acid with the formula HSCH2CH2CHCO2H. It is a homologue of the amino acid cysteine, differing by an additional methylene group. It is biosynthesized from methionine by the removal of its terminal Cε methyl group...
and tetrahydrofolate (Katzung, 1989). Cobalamins are characterized by a porphyrin
Porphyrin
Porphyrins are a group of organic compounds, many naturally occurring. One of the best-known porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin. Porphyrins are heterocyclic macrocycles composed of four modified pyrrole subunits interconnected at...
-like corrin
Corrin
Corrin is an heterocyclic compound. It is the parent macrocycle related to substituted derivative that is found in vitamin B12. Its name reflects that it is the "core" of vitamin B12 .-Coordination chemistry:...
nucleus that contains a single cobalt
Cobalt
Cobalt is a chemical element with symbol Co and atomic number 27. It is found naturally only in chemically combined form. The free element, produced by reductive smelting, is a hard, lustrous, silver-gray metal....
atom bound to a benzimidazolyl nucleotide and a variable residue (R) group. The variable R group gives rise to the four most commonly known cobalamins: CNCbl
Cyanocobalamin
Cyanocobalamin is an especially common vitamer of the vitamin B12 family. It is the most famous vitamer of the family, because it is, in chemical terms, the most air-stable...
, methylcobalamin, 5-deoxyadenosylcobalamin
Cobamamide
Cobamamide , which is also known as adenosylcobalamin and dibencozide, is, along with methylcobalamin , one of the active forms of vitamin B12...
, and OHCbl. In the serum, OHCbl and CNCbl are believed to function as storage or transport forms of the molecule; whereas, methylcobalamin and 5¢ deoxyadenosylcobalamin are the active forms of the coenzyme required for cell growth and replication (Katzung, 1989). CNCbl is usually converted to OHCbl in the serum, whereas OHCbl is converted to either methylcobalamin or 5¢ deoxyadenosyl cobalamin. Cobalamins circulate bound to serum proteins called transcobalamins (TC) and haptocorrins
Haptocorrin
Haptocorrin also known as transcobalamin-1 is a protein that in humans is encoded by the TCN1 gene. The essential function of haptocorrin is protection of the acid-sensitive vitamin B12 while it moves through the stomach.- Function :...
. OHCbl has a higher affinity to the TC II transport protein than CNCbl, or 5- deoxyadenosylcobalamin. From a biochemical point of view, two essential enzymatic reactions require vitamin B12 (cobalamin) (Katzung, 1989, Hardman, 2001). Intracellular
Intracellular
Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
vitamin B12 is maintained in two active coenzymes, methylcobalamin and 5¢ deoxyadenosylcobalamin, which are both involved in specific enzymatic reactions. In the face of vitamin B12 deficiency, conversion of methylmalonyl-CoA to succinyl-CoA
Succinyl-CoA
Succinyl-Coenzyme A, abbreviated as Succinyl-CoA or SucCoA, is a combination of succinic acid and coenzyme A.-Source:It is an important intermediate in the citric acid cycle, where it is synthesized from α-Ketoglutarate by α-ketoglutarate dehydrogenase through decarboxylation...
cannot take place, which results in accumulation of methylmalonyl CoA and aberrant fatty acid synthesis. In the other enzymatic reaction, methylcobalamin supports the methionine synthase reaction, which is essential for normal metabolism of folate. The folate-cobalamin interaction is pivotal for normal synthesis of purines and pyrimidines and the transfer of the methyl group to cobalamin is essential for the adequate supply of tetrahydrofolate, the substrate for metabolic steps that require folate. In a state of vitamin B12 deficiency, the cell responds by redirecting folate metabolic pathways to supply increasing amounts of methyltetrahydrofolate
Levomefolic acid
Levomefolic acid or metafolin is the natural, active form of folic acid used at the cellular level for DNA reproduction, the cysteine cycle and the regulation of homocysteine among other functions. The un-methylated form, folic acid , is a synthetic form of folate found in nutritional supplements...
. The resulting elevated concentrations of homocysteine
Homocysteine
Homocysteine is a non-protein amino acid with the formula HSCH2CH2CHCO2H. It is a homologue of the amino acid cysteine, differing by an additional methylene group. It is biosynthesized from methionine by the removal of its terminal Cε methyl group...
and MMA are often found in patients with low serum vitamin B12 and can usually be lowered with successful vitamin B12 replacement therapy. However, elevated MMA and homocysteine concentrations may persist in patients with cobalamin concentrations between 200 to 350 pg/mL (Lindenbaum et al. 1994). Supplementation with vitamin B12 during conditions of deficiency restores the intracellular level of cobalamin and maintains a sufficient level of the two active coenzymes: methylcobalamin and deoxyadenosylcobalamin.
External links
- Hydroxocobalamin in the ChEBIChEBIChemical Entities of Biological Interest, also known as ChEBI, is a database and ontology of molecular entities focused on 'small' chemical compounds, that is part of the Open Biomedical Ontologies effort...
database