Published June 9, By Dr.
Pernicious anemia is a megaloblastic anemia resulting from vitamin B12 deficiency that develops as a result of a lack of intrinsic factor being released from stomach parietal cells leading to subsequent malabsorption of the vitamin. The major cause of the loss of intrinsic factor is an autoimmune destruction of the parietal cells that secrete it.
Surgical removal of a part of the stomach can also result in loss of intrinsic factor resulting in pernicious anemia.
In rare cases individuals inherit mutation in the GIF gene that encodes intrinsic factor resulting in pernicious anemia. The pernicious anemias result from impaired DNA synthesis due to a block in purine and thymidine biosynthesis. The block in nucleotide biosynthesis is a consequence of the effect of vitamin B12 on folate metabolism.
When vitamin B12 is deficient essentially all of the folate becomes trapped as the N5-methylTHF 5-methylTHF; or simply methylTHF derivative as a result of the loss of functional methionine synthase also called homocysteine methyltransferase. This trapping prevents the synthesis of other THF derivatives required for the purine and thymidine nucleotide biosynthesis pathways.
Neurological complications also are associated with vitamin B12 deficiency and result from a progressive demyelination of nerve cells. The demyelination is thought to result from the increase in methylmalonyl-CoA that results from vitamin B12 deficiency that is associated with loss of methylmalonyl-CoA mutase activity.
The loss of methylmalonyl-CoA mutase activity with deficiencies in B12 results in an accompanying methylmalonic acidemia. Methylmalonyl-CoA is a competitive inhibitor of malonyl-CoA in fatty acid biosynthesis as well as being able to substitute for malonyl-CoA in any fatty acid biosynthesis that may occur.
Since the myelin sheath that protects nerve cells is in continual flux the methylmalonyl-CoA-induced inhibition of fatty acid synthesis results in the eventual destruction of the sheath.
The incorporation methylmalonyl-CoA into fatty acid biosynthesis results in branched-chain fatty acids being produced that may severely alter the architecture of the normal membrane structure of nerve cells. Contributing to the neural degeneration seen in vitamin B12 deficiency is the reduced synthesis of S-adenosylmethione SAM; also abbreviated AdoMet due to loss of the methionine synthase catalyzed reaction.
The conversion of phosphatidylethanolamine PE to phosphatidylcholine PC requires the enzyme phosphatidylethanolamine N-methyltransferase encoded by the PEMT gene which carries out three successive SAM-dependent methylation reactions.
This reaction is a critically important reaction of membrane lipid homeostasis. Therefore, the reduced capacity to carry out the methionine synthase reaction, due to nutritional or disease mediated deficiency of vitamin B12results in reduced SAM production and as a consequence contributes to the neural degeneration i.
Deficiencies in B12 can also lead to elevations in the level of circulating homocysteine and elevated excretion of the oxidized dimer of homocysteine called homocystine. Elevated levels of homocysteine are known to lead to cardiovascular dysfunction.
Due to its high reactivity to proteins, homocysteine is almost always bound to proteins, thus thiolating them leading to their degradation. Homocysteine also binds to albumin and hemoglobin in the blood.
Some of the detrimental effects of homocysteine are due to its' binding to lysyl oxidase, an enzyme responsible for proper maturation of the extracellular matrix proteins collagen and elastin.
Production of defective collagen and elastin has a negative impact on arteries, bone, and skin and the effects on arteries are believed to be the underlying cause for cardiac dysfunction associated with elevated serum homocysteine. The increased risk for thrombotic episodes, such as deep vein thrombosis DVTassociated with homocysteinemia is due to homocysteine serving as a contact activation nucleus for activation of the intrinsic coagulation cascade.
Folic acid is sometimes referred to as vitamin B9. The terms folic acid and folate are sometimes used interchangeably but from a dietary perspective they are distinctly different.
The term folate should be used to refer only to the bioactive forms of folic acid, namely dihydrofolate DHF and tetrahydrofolate THF and their derivatives. Folic acid is a conjugated molecule consisting of a pteridine ring structure linked to para-aminobenzoic acid PABA that forms pteroic acid.
Pteroic acid is then converted to folic acid through the N-esterification of glutamic acid to the carboxylic acid of the PABA portion of pteroic acid.Enzyme catalysis is the increase in the rate of a chemical reaction by the active site of a ashio-midori.com protein catalyst may be part of a multi-subunit complex, and/or may transiently or permanently associate with a Cofactor (e.g.
adenosine triphosphate). Catalysis of biochemical reactions in the cell is vital due to the very low reaction rates of the uncatalysed reactions at room temperature. Enzymes / ˈ ɛ n z aɪ m z / are macromolecular biological ashio-midori.coms accelerate chemical ashio-midori.com molecules upon which enzymes may act are called substrates and the enzyme converts the substrates into different molecules known as ashio-midori.com all metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life.
Types of Biochemical Reactions. Hydrophobic Effect Electrostatic and van der Waals Interactions Acid‐Base Reactions in Living Systems United Strength of Biochemical Structures Six Types of Enzyme Catalysts Energy Production Biosynthetic versus Catabolic Reactions.
C-reactive protein (CRP) a protein that is produced in the liver in response to ashio-midori.com is a biomarker of inflammation that is strongly associated with the risk of cardiovascular events, such as myocardial infarction and stroke. Calcification the process of deposition of calcium salts.
In the formation of bone this is a normal condition. Cofactors. The catalytic activity of many enzymes depends on the presence of small molecules termed cofactors, although the precise role varies with the cofactor and the ashio-midori.com an enzyme without its cofactor is referred to as an apoenzyme; the complete, catalytically active enzyme is called a holoenzyme..
Cofactors can be subdivided into two groups: metals and small organic molecules. Welcome to ashio-midori.com Replagal (agalsidase alfa for infusion) is indicated for long-term ERT (enzyme replacement therapy) in patients with a confirmed diagnosis of Fabry disease (α-galactosidase A deficiency).
1 Replagal is currently the only human cell line-derived form of the human protein α-galactosidase A that is commercially available. 1,2.