Vitamins Are Often Precursors to Coenzymes - Biochemistry - NCBI Bookshelf
The most prominent function of the vitamins is to serve as cofactors A highly diagnostic physical test of thiamine deficiency is vertical. What are the vitamin B12 coenzyme forms? of yeast and probiotics in connection with specialized nutrient solutions, which contain synthetic vitamins or their. coenzymes and vitamins study guide by taylor_nicolle9 includes 27 questions covering vocabulary, terms and more. Quizlet flashcards, activities and games.
So two great examples are ones we just discussed. Vitamin B3, which you may see being called niacin on a food label, is actually just a precursor for NAD. And vitamin B5 is just a precursor for co-enzyme A. Minerals, on the other hand, are inorganic, meaning they aren't carbon based.
And minerals are usually just co-factors in our body. So magnesium would be a great example of a mineral co-factor that an enzyme like DNA polymerase would use. Now, not all minerals act only as co-factors. Some minerals, like calcium, which can act as a co-factor, is also a critically important component of bone and teeth.
Co-factors, co-enzymes, and vitamins
And it doesn't strictly act as an enzyme co-factor here. It's actually an important part of the structure itself. So what did we learn? Well, first we learned that not all enzymes are able to function alone and some need a little help. And next, we learned that this help can come from co-enzymes, which usually act as carrier molecules, or co-factors, which directly assist with the catalysis that the enzyme is doing.
And finally, we learned that the vitamins and minerals generally refer to dietary co-factors and co-enzymes. 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.
Chapter 6. The Vitamins
This latter structure is the form of "folate" present in dietary supplements and when used to fortify manufactured food products. Dietary folates which are predominately the N5-methylTHF form; 5-methyl-THF are obtained primarily from yeasts and leafy vegetables as well as animal liver.
When ingested from natural sources, or when stored in cells predominantly in the liver and the kidneysfolates exists in a polyglutamate form.
Jejunal small intestine mucosal cells remove the glutamate residues to the monoglutamate state through the action of the enzyme, folate hydrolase 1 which is encoded by the FOLH1 gene. Folate hydrolase 1 is also commonly called glutamate carboxypeptidase II. Within the intestinal enterocytes, the monoglutamate forms of the folates are less negatively charged compared to the polyglutamic acidsand are therefore, more capable of being transported across the basolateral membrane facing the blood of the jejunal enterocytes and into the bloodstream.
The function of the GGH encoded enzyme is to remove polyglutamates from intracellular stores of the folate derivatives that, as indicated, are predominantly stored in the liver and the kidneys. The GGH encoded enzyme is localized to the lysosomes. The function of the GGH encoded enzyme is to release glutamates from stored folates so that the monoglutamate forms can be excreted into the blood to meet systemic needs.
Folates in the diet are predominantly the N5-methyltetrahydrofolate 5-methyl-THF form. Another folate transporter, that was originally thought to be the major intestinal folate uptake transporter, was originally identified as the reduced folate carrier RFC. Outside the intestine cellular folate uptake, particularly cells in the central nervous system, is carried out by the SLC46A1 encoded transporter.
The activity of RFC-mediated folate transport is highest for reduced folates hence the name such as 5-methyl-THF with very low affinity for folic acid.
The RFC is also utilized in the uptake of the anti-folate drugs such as methotrexate and palatrexate. RFC functions as an antiporter with organic phosphate being transported out of the cell in exchange for folate uptake. The critical role of the SLC46A1 encoded transporter in intestinal folate absorption is evident in individuals with an inherited form of folate malnutrition hereditary folate malabsorption, HFM that results from mutations in the SLC46A1 gene.
The SLC46A1 gene is located on chromosome 17q Interestingly there are transporters of the multidrug resistance family that can efflux folates from the intestinal enterocyte back into the lumen of the intestines. Both transporters have been shown to efflux folates from intestinal enterocytes and, as such, can compete with the activity of PCFT in folate uptake.
Another member of the multidrug resistance protein family, multidrug resistance-associated protein 3 MRP3; encoded by the ABCC3 geneis expressed in the basolateral membrane of intestinal enterocytes and transports folic acid and 5-methyl-THF into the blood. Another important protein involved in folate transport in the adult human is the FOLR1 folate receptor 1 encoded receptor protein.
The FOLR1 gene is located on chromosome 11q The FOLR1 gene represents one member of a family of folate receptor genes that are clustered at the 11q The FOLR2 gene is referred to as the fetal folate receptor gene given it was originally identified as being expressed in the placenta.
The FOLR3 gene is expressed in bone marrow, thymus, and spleen, and its expression is elevated in ovarian and uterine cancers. The FOLR3 protein is exclusively secreted. In an anti-anaemic factor was found in liver and called vitamin BC.
These were later shown to be the same substance with folic acid as the active ingredient. Folic acid was synthesized in and was soon used in fish diets for preventing purified diet anaemia.
It can be precipitated with heavy metal salts. It is stable to heat in neutral or alkaline solution, but unstable in acid solution. It deteriorates when exposed to sunlight, or during prolonged storage.
Coenzymes, Cofactors & Prosthetic Groups: Function and Interactions
Several analogues have biological activity including pteroic acid, rhizopterin, folinic acid, xanthopterin and several formyltetrahydropteroyl-glutamic acid derivatives. These have closely allied ring structures and many have been isolated as derivatives in various animals or microbiological preparations. One simple form, xanthopterin, present in the pigments of insects, is shown below and is of special interest because of early work with this compound as the anti-anaemic factor H for fish.
In the presence of ascorbic acid, folic acid is transformed into the active 5-formyl-5, 6,7,8 tetrahydrofolic acid. Folic acid is involved in many one-carbon metabolism systems such as serine and glycine interconversion, methionine-homocysteine synthesis, histidine synthesis, and pyrimidine synthesis.
Several coenzyme forms of the active vitamin have been isolated. Folic acid is involved in the conversion of megaloblastic bone marrow to normoblastic type. It has a role in blood glucose regulation and improves cell membrane function and hatchability of eggs. Increasing numbers of senile cells are observed as the deficiency progresses until only a few old and degenerating cells are found in the blood of deficient fish.
Anterior kidney imprints disclose only adult cells and no preforms present. Other signs observed have been poor growth, anorexia, general anaemia, lethargy, fragile fins, dark skin pigmentation, and infarction of spleen. The requirement seems to be about the same for trout and salmon. Marginal macrocytic anaemias occur in fish fed diets containing marginal amounts of folacin.
Individual fish ingesting adequate amounts of the vitamin show little variation in total erythrocyte counts. Insects contain xanthopterin which has folic acid activity. At one time the yellow pigment of xanthopterin was identified as the fish anti-anaemic factor H, but subsequent experiments showed only partial activity and that folic acid itself was a much more potent antimacrocytic anaemia factor.
Insects may contribute significantly to the folic acid requirements of wild fish, but in scientific fish husbandry artificial diets are more reliable sources.
Activity is lost during extended storage and when material is exposed to sunlight. Therefore, dry feeds should be carefully protected during manufacture and moist diet rations should be carefully preserved. Both types of fish diets should be fed soon after manufacture to assure minimal loss of folic acid activity.
Co-factors, co-enzymes, and vitamins (video) | Khan Academy
This material, when incorporated in the diet of guinea pigs and rats, induces anaemia and leucopenia and has been used to treat leukemia in man. Amethopterin 4-amino-Nmethylpteroylglutamic acid can also be used to induce deficiency by inhibiting purine, pyrimidine, and nucleic acid protection; viz. Anterior kidney imprints easily disclose normal distribution of immature cells and preforms undergoing reticulosis.
Microbiological assay is preferred for assessment of total folic acid in dietary raw materials because the total biological activity it measures includes all the various coenzyme forms and folic acid analogues.
Assessment of the dietary intake of folic acid is important for intensive cold water fish husbandry. In pond culture, aquatic and terrestrial insects, algae, etc. Since folic acid is labile in storage, excess amounts are generally added to manufactured feed in anticipation of storage losses. However, prudent fish husbandry dictates rapid use of manufactured rations with minimum storage. Routine periodic haematology of fish assures proper nutritional status for maximum production and sound health.
The author has noted in several series of experiments that when fish diseases occur through inadvertent contamination of the water supply, those groups of fish partially or completely deficient in folic acid were among the first to show acute disease symptoms. Therefore, folic acid must also play an important role in resistance to disease.
This substance, named vitamin B12 by its discoverers, was later to be recognized as essential for growth of chicken fed diets entirely of plant origin and was designated animal protein factor APF. When anaemic salmon were injected with crystalline B12 in combination with folic acid and xanthopterin positive haemopoiesis occurred within a few days, and the salmon showed rapid recovery from the anaemia.
Cyanocobalamin The molecule has a planar group and a nucleotide group lying nearly at right angles to one another. This cobalt-containing vitamin has a net charge of one at the central cobalt atom to which is attached a replaceable cyano group. Vitamin B12 is stable to mild heat in neutral solution, but is rapidly destroyed by heating in dilute acid or alkali. Crude concentrates are more unstable and rapidly lose activity.
The compound is similar to the porphyrins in its spatial configuration with a central cobalt atom linked to four reduced pyrrole rings in the haeme series. Replacing the cyanide ion with a variety of anions produce derivatives which have comparable biological activities; viz. It is required by many micro-organisms and is a growth factor for many animals. The animal protein factor present in fish and animal by-products was not recognized until crystalline vitamin B12 was injected into anaemic chinook salmon fingerlings in and positive haemopoiesis was observed.
A coenzyme incorporating vitamin B12 is involved in the reversible isomerization of methyl-malonyl coenzyme A to succinyl coenzyme A and in the isomerization of methylaspartate to glutomate. Cyanocobalamin is involved in the coenzyme for the methylation of homocystine to form methionine. It is also involved in several other one-carbon reactions and in the synthesis of labile methyl compounds.
One vitamin B12 containing coenzyme acts in methylation of the purine ring during thymine synthesis.
Vitamin B12 is also involved in cholesterol metabolism, in purine and pyrimidine biosynthesis, and in the metabolism of glycols. An intrinsic factor is necessary for good absorption of the vitamin from the gut.
This factor is a low molecular weight mucoprotein which normally occurs in gastric juice, and especially in hog gut mucosa. Pernicious anaemia in chinook and coho salmon is characterized by fragmented, erythrocytes with many aberrant forms present.
Haemoglobin levels are inconsistent and erythrocyte counts have a range extending from frank anaemia to a near normal blood pattern. Cyanocobalamin stores in fish tissues are slowly exhausted and only after weeks on test do the symptoms appear in deficient salmon populations. Poor appetite, poor growth, poor food conversion, and some dark pigmentation can be observed before frank anaemia is detected.
Since vitamin B12 is labile on storage, and in mild acid solution is easily destroyed by heating, care must be exercised in diet preparation containing flesh or meat scraps. The vitamin B12 coenzymes are very unstable under light, which rapidly decomposes the coenzymes. Photo-sensitivity is increased in dilute acid solutions. Prompt response in individual fish is obtained by injecting B12 alone or in combination with folic acid in the ratio of 1 part vitamin B12 to parts folic acid.
Careful interpretation of haemotological data will enable one to distinguish one form of anaemia from the other. King of the U.
Vitamin C synthesis was accomplished in after the chemical structure of ascorbic acid was established by British and Swiss workers. McCay and Tunison reported scoliosis in brook trout fed formalin-preserved meat in and McLaren observe haemorrhages in trout fed rations low in ascorbic acid. It was not until the sixties that a critical need for L-ascorbic acid by trout and salmon was demonstrated.
It is readily oxidized to dehydroascorbic acid, the less biologically potent form. Ascorbic acid is very stable in acid solution because of the preservation of the lactone ring, but in alkaline solution hydrolysis occurs rapidly and vitamin activity is lost. It is very heat labile and prone to atmospheric oxidation, especially in the presence of copper, iron, or several other metallic catalysts.
The reduced form is the most biologically active but several derivatives or salts are obtainable which have varying degrees of ascorbate activity. It is involved in many enzyme systems for hydroxylation; i. It is involved in the detoxification of aromatic drugs and also acts in the production of adrenal steroids.
Ascorbic acid is necessary for the formation of hydroxy proline which is a constituent of collagen, a component of intercellular material in bones and soft tissues. Ascorbic acid plays a synergistic role with vitamin E as intracellular antioxidants and free radical traps.
The conversion of folic acid to folinic acid requires vitamin C. Ascorbic acid is involved in the formation of chondroitin sulphate and intercellular ground substance. Labelled ascorbic acid fed to fish previously deficient in the vitamin was shown to be rapidly mobilized and fixed in areas of rapid collagen synthesis and became concentrated in the thick collagen of the skin and in cartilagenous bones, as well as in the glands of the anterior kidney.
Ascorbic acid is also involved in erythrocyte maturation. Deficiency signs in fish are generally related to impaired collagen formation.
- Natural Vitamins and Coenzyme Forms
- Vitamins: Water and Fat Soluble
Fish soon show hyperplasia of jaw and snout. The same symptoms have been observed in trout, salmon, yellowtail, carp, guppies and char. Histologically, hypertrophy of the adrenal tissues and haemorrhage at the bases of fins have been observed in coho salmon. Deficiency signs cease to develop and new growth becomes normal upon replacement of ascorbic acid in the ration.
Anaemia eventually develops in extremely deficient fish and scoliosis and lordosis do not repair but are walled off by new growth around the afflicted areas of the spine when ascorbic acid is once again added to the ration. When wound repair experiments were initiated, however, or when fish were exposed to other stress then the requirements doubled or tripled. Coho salmon appear to need about half of these requirements for adequate tissue levels and for maximum severe wound repair rates.
This phenomenon is illustrated in Table 4 showing growth response and tissue repair for rainbow trout and coho salmon. The requirement for ascorbic acid is related to stress, growth rate and size of the animal, as well as to the other nutrients present in the diet.Enzymes