Pyridoxine metabolism

Defective erythropoiesis (dyserythropoiesis) impaired hemoglobin synthesis leading to lack of utilization and consequent accumulation of iron in mitochondria, e.g., from inhibition of ALA synthase activity by dietary vitamin 85 deficiency inhibition of heme synthesis by lead impairment of pyridoxine metabolism in alcoholic patients familial sideroblastic anemias and Cooley s anemia. 

In cats, pyridoxine deficiency is associated with the formation of calcium oxalate calculi in the kidneys. The magnesium and pyridoxine levels in the diet are related. Diets low in magnesium are responsible for increased incidence and severity of the oxalate lithiasis in the kidney, and the effect of the low-magnesium diet is counteracted by the administration of pyridoxine. These observations made in animals may have some relevance to the development of lithiasis in humans. Patients with recurring calcium oxalate stones in the kidney secrete more xanthurenic and pyridoxic acid than normal individuals, suggesting that lithiasis may result from deficient pyridoxine metabolism, possibly due to accelerated breakdown of the coenzyme. If other signs of pyridoxine deficiency develop, one must assume that the accelerated breakdown occurs only in a few organs, probably only in the kidneys. 

The combination of GC with mass spectrometry has been used to study pyridoxine metabolism in tumor cells. Using radiolabeled PN and paired-ion, reversed-phase HPLC, Tryfiates and coworkers (158) demonstrated that about 30% of the radiolabel was associated with a product showing a retention time different from any of the known B vitamers. Using mass spectrometry, with and without prior GLC separation, the product was eventually identified as adenosine-N -diethylthioether-N -pyridoximine-5 -phosphate (158,159). Recent studies from Tryfiates and Bishop indicate that the above-mentioned novel Be vitamer... 

There is evidence that some people are sensitive to free glutamates. These people get headaches or other symptoms if they ingest too much. This may be related to pyridoxine (vitamin B6) deficiencies, as this vitamin is necessary for glutamate metabolism. People with uncontrolled severe asthma may find that glutamates complicate or worsen their symptoms. 

Be Pyridoxine, pyridoxal, pyridoxamine Coenzyme in transamination and decarboxylation of amino acids and glycogen phosphorylase role in steroid hormone action Disorders of amino acid metabolism, convulsions... 

Pantothenic acid is present in coenzyme A and acyl carrier protein, which act as carriers for acyl groups in metabolic reactions. Pyridoxine, as pyridoxal phosphate, is the coenzyme for several enzymes of amino acid metabolism, including the aminotransferases, and of glycogen phosphorylase. Biotin is the coenzyme for several carboxylase enzymes. 

Rice bran is the richest natural source of B-complex vitamins. Considerable amounts of thiamin (Bl), riboflavin (B2), niacin (B3), pantothenic acid (B5) and pyridoxin (B6) are available in rice bran (Table 17.1). Thiamin (Bl) is central to carbohydrate metabolism and kreb s cycle function. Niacin (B3) also plays a key role in carbohydrate metabolism for the synthesis of GTF (Glucose Tolerance Factor). As a pre-cursor to NAD (nicotinamide adenine dinucleotide-oxidized form), it is an important metabolite concerned with intracellular energy production. It prevents the depletion of NAD in the pancreatic beta cells. It also promotes healthy cholesterol levels not only by decreasing LDL-C but also by improving HDL-C. It is the safest nutritional approach to normalizing cholesterol levels. Pyridoxine (B6) helps to regulate blood glucose levels, prevents peripheral neuropathy in diabetics and improves the immune function. 

The water-soluble vitamins generally function as cofactors for metabolism enzymes such as those involved in the production of energy from carbohydrates and fats. Their members consist of vitamin C and vitamin B complex which include thiamine, riboflavin (vitamin B2), nicotinic acid, pyridoxine, pantothenic acid, folic acid, cobalamin (vitamin B12), inositol, and biotin. A number of recent publications have demonstrated that vitamin carriers can transport various types of water-soluble vitamins, but the carrier-mediated systems seem negligible for the membrane transport of fat-soluble vitamins such as vitamin A, D, E, and K. 

The transsulfuration pathway is the major route for the metabolism of the sulfur-containing amino adds 674 Homocystinuria is the result of the congenital absence of cystathionine synthase, a key enzyme of the transsulfuration pathway 676 Homocystinuria can be treated in some cases by the administration of pyridoxine (vitamin B6), which is a cofactor for the cystathionine synthase reaction 676... 

Homocystinuria Usually a failure of cystathionine synthase (Fig. 40-2 reaction 6). Rarely associated with aberrant vitamin B12 metabolism (Fig. 40-2) Thromboembolic diathesis, marfanoid habitus, ectopia lentis. Mental retardation is frequent. Diet low in methionine Vitamin B6 in pyridoxine-responsive syndromes Vitamin B12 in responsive syndromes Anticlotting agents... 

Vitamin Ba (pyridoxine, pyridoxal, pyridoxamine) like nicotinic acid is a pyridine derivative. Its phosphorylated form is the coenzyme in enzymes that decarboxylate amino acids, e.g., tyrosine, arginine, glycine, glutamic acid, and dihydroxyphenylalanine. Vitamin B participates as coenzyme in various transaminations. It also functions in the conversion of tryptophan to nicotinic acid and amide. It is generally concerned with protein metabolism, e.g., the vitamin B8 requirement is increased in rats during increased protein intake. Vitamin B6 is also involved in the formation of unsaturated fatty acids. 

Group-transfer reactions often involve vitamins3, which humans need to have in then-diet, since we are incapable of realizing their synthesis. These include nicotinamide (derived from the vitamin nicotinic acid) and riboflavin (vitamin B2) derivatives, required for electron transfer reactions, biotin for the transfer of C02, pantothenate for acyl group transfer, thiamine (vitamin as thiamine pyrophosphate) for transfer of aldehyde groups and folic acid (as tetrahydrofolate) for exchange of one-carbon fragments. Lipoic acid (not a vitamin) is both an acyl and an electron carrier. In addition, vitamins such as pyridoxine (vitamin B6, as pyridoxal phosphate), vitamin B12 and vitamin C (ascorbic acid) participate as cofactors in an important number of metabolic reactions. 

The last of the B vitamins to be identified in the water-soluble vitamin complex from milk was pyridoxine, vitamin B6 (Birch and Gyorgy, 1936). This was needed to prevent a type of dermatitis in rats which was different from pellagra or acrodynia and could be accompanied by convulsions. Much of the early work on the mode of action of this vitamin came from experiments on microbial metabolism (Chapter 6). 

A group of enzymes which is particularly important in amino acid metabolism in the liver (and also in muscle) is the transaminases, (also called aminotransferases). These are vitamin B6 (pyridoxine) dependent enzymes which transfer an amino group from an amino acid to an oxo (keto) acid, thus ... 

Vitamin Be is again a small family of related compounds having the same biological activity. These include pyridoxine, pyridoxai, and pyridoxamine. In humans, these molecules are readily interconverted, accounting for their equivalence as vitamins. The stuff in your vitamin pill is likely to be pyridoxine. The actual molecule that functions as a coenzyme in metabolism is pyridoxai phosphate, in which a phosphate group has been added to pyridoxai in an ATP-dependent reaction. 

Be (pyridoxine) Meats, cereals, lentils, nuts, some fruits and vegetables Amino acid metabolism... 

Pyridoxine (vitamin Be) is essential for protein metabolism and plays an important role in hemoglobin production. Pyridoxamine and pyri-doxal also possess vitamin Be activity. Sources of... 

Geriatric Considerations - Summary Age is not a contraindication to INH prophylaxis or treatment of tuberculosis. Follow adult guidelines for treatment. INH maybe used in patient wit h stable hepatic disease. The risk of clinical hepatitis increases with age and has been reported in 2% of adults aged greater than 50. INH interferes with the metabolism of pyridoxine therefore concomitant pyridoxine therapy at 25mg/day is recommended to prevent neurotoxicity. INH is metabolized via acetylation in the liver. Older adults who are slow acetylators of the drug may require lower doses to achieve effective serum concentrations and prevent adverse effects. Food, especially high-fat meals, delays and reduces absorption therefore administer INH on an empty stomach. 

Mechanism of Action Acts as a coenzyme for various metabolic functions, including metabolism of proteins, carbohydrates, and fats. Aids in the breakdown of glycogen and in the synthesis of gamma-aminobutyric acid in the CNS. Therapeutic Effect Prevents pyridoxine deficiency. Increases the excretion of certain drugs, such as iso-niazid, that are pyridoxine antagonists. 

Pharmacologic doses of pyridoxine (vitamin B6 ) enhance the extracerebral metabolism of levodopa and may therefore prevent its therapeutic effect unless a peripheral decarboxylase inhibitor is also taken. Levodopa should not be given to patients taking monoamine oxidase A inhibitors or within 2 weeks of their discontinuance because such a combination can lead to hypertensive crises. 

Miscellaneous other reactions include hematologic abnormalities, provocation of pyridoxine deficiency anemia, tinnitus, and gastrointestinal discomfort. Isoniazid can reduce the metabolism of phenytoin, increasing its blood level and toxicity. 

Vitamin B6 occurs naturally in three related forms pyridoxine (6.26 the alcohol form), pyridoxal (6.27 aldehyde) and pyridoxamine (6.28 amine). All are structurally related to pyridine. The active co-enzyme form of this vitamin is pyridoxal phosphate (PLP 6.29), which is a co-factor for transaminases which catalyse the transfer of amino groups (6.29). PLP is also important for amino acid decarboxylases and functions in the metabolism of glycogen and the synthesis of sphingolipids in the nervous system. In addition, PLP is involved in the formation of niacin from tryptophan (section 6.3.3) and in the initial synthesis of haem. 

All aminotransferases have the same prosthetic group and the same reaction mechanism. The prosthetic group is pyridoxal phosphate (PLP), the coenzyme form of pyridoxine, or vitamin B6. We encountered pyridoxal phosphate in Chapter 15, as a coenzyme in the glycogen phosphorylase reaction, but its role in that reaction is not representative of its usual coenzyme function. Its primary role in cells is in the metabolism of molecules with amino groups. 

The homocystinurias are a group of disorders involving defects in the metabolism of homocysteine. The diseases are inherited as autosomal recessive illnesses, characterized by high plasma and urinary levels of homocysteine and methionine and low levels of cysteine. The most common cause of homocystinuria is a defect in the enzyme cystathionine /3-synthase, which converts homocysteine to cystathionine (Figure 20.21). Individuals who are homozygous for cystathionine [3-synthase deficiency exhibit ectopia lentis (displace ment of the lens of the eye), skeletal abnormalities, premature arte rial disease, osteoporosis, and mental retardation. Patients can be responsive or non-responsive to oral administration of pyridoxine (vitamin B6)—a cofactor of cystathionine [3-synthase. Bg-responsive patients usually have a milder and later onset of clinical symptoms compared with B6-non-responsive patients. Treatment includes restriction of methionine intake and supplementation with vitamins Bg, B, and folate. 

Vitamins are chemically unrelated organic compounds that cannot be synthesized by humans and, therefore, must must be supplied by the diet. Nine vitamins (folic acid, cobalamin, ascorbic acid, pyridoxine, thiamine, niacin, riboflavin, biotin, and pantothenic acid) are classified as water-soluble, whereas four vitamins (vitamins A, D, K, and E) are termed fat-soluble (Figure 28.1). Vitamins are required to perform specific cellular functions, for example, many of the water-soluble vitamins are precursors of coenzymes for the enzymes of intermediary metabolism. In contrast to the water-soluble vitamins, only one fat soluble vitamin (vitamin K) has a coenzyme function. These vitamins are released, absorbed, and transported with the fat of the diet. They are not readily excreted in the urine, and significant quantities are stored in Die liver and adipose tissue. In fact, consumption of vitamins A and D in exoess of the recommended dietary allowances can lead to accumulation of toxic quantities of these compounds. 

Vitamin B6 (pyridoxine, pyridoxamine, and pyridoxal) has the active form, pyridoxal phosphate. It functions as a cofactor for enzymes, particularly in amino acid metabolism. Deficiency of this vitamin is rare, but causes glossitis and neuropathy. The deficiency can be induced by isoniazid, which causes sensory neuropathy at high doses. 

Thiamine, biotin and pyridoxine (vitamin B) coenzymes are grouped together because they catalyze similar phenomena, i.e., the removal of a carboxyl group, COOH, from a metabolite. However, each requires different specific circumstances. Thiamine coenzyme decarboxylates only alpha-keto acids, is frequently accompanied by dehydrogenation, and is mainly associated with carbohydrate metabolism. Biotin enzymes do not require the alpha-keto configuration, are readily reversible, and are concerned primarily with lipid metabolism. Pyridoxine coenzymes perform nonoxidative decarboxylation and are closely allied with amino acid metabolism. 

VITAMIN B (Pyridoxine). Infrequently called adermine or pyridoxol, this vitamin participates in protein, carbohydrate, and lipid metabolism. The metabolically active form of B6 is pyridoxal phosphate, the structures of which are ... 

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