PYRIDOXINE

1. PYRIDOXINE M.Prasad Naidu MSc Medical Biochemistry, Ph.D,.

2. Pyridoxine Pyridoxamine Pyridoxal In the diet it exists in the form of Pyridoxine easily converted to other forms in the body.

4. Co enzyme PYRIDOXAL PHOSPHATESynthesized by pyridoxalkinaseutilising ATP. Pyridoxal + ATP kinase PLP The Aldehyde (CHo) group of PLP is attached to Epsilon Amino group of Lysine of Apoenzyme. PLP

6. : Pyridoxal is present in the tissues as its coenzyme form, pyridoxal phosphate. Pyridoxal phosphate is mainly distributed in the liver, brain, kidney and muscle. Excretion: 4-pyridoxic acid is the major metabolite of pyridoxine. It is mainly excreted in the urine.

7. Functions of PLP PLP ACTS AS CO ENZYME MAINLY IN AMINO ACID METABOLISM IT ALSO ACTS AS COENZYME IN LIPID ;AND CARBOHYDRATE METABOLISM ;; FEW OF METABOLIC REACTIONS Trasamination Reactions of Amino Acids Transamination reactions are reaquired for the catabolism of amino acids as well as gluconeogenesis. PLP is cofactor for transaminases such as aspartatetransaminase; alaninetransaminase, phenylalanine transaminase and tyrosine transaminase.

8. Aspartate amino transferase catalyzes the transmination of aspartate to form oxaloacetate.

9. Alanine amino transferase Alanine amino transferase catalyzes the transamination of alanine to form pyruvate

10. Non-oxidative deamination of amino acids Pyridoxal phosphate is involved in the catabolism of amino acids. These reactions are examples for non-oxidative deamination of amino acids. Serine dehydratase Catalyzes the conversion of serine

12. Threoninedehydratase Serine dehydratase catalyzes the conversion of threonine to α-ketobutyrate.

13. Histidase Catalyzes the conversion of histidine to urocanate

14. Cysteinedesulfhydrase Catalyzes the conversion of cysteine to pyruvate, NH3 and hydrogn sulfide.

15. Amino Acid Decarboxylations Pyridoxal phosphate is required for the decarboxylation reactions of amino acids These reactions are involved in the biosynthesis of biogenic amines. Eg: Glutamate decarboxylase catalyzes the decarboxylation of glutamate to γ amino butyric acid (GABA). GABA is an inhibitory neurotransmitter.

17. Histadinedecarboxylase Catalyzes the conversion of histidine to histamine. Histamine is an important compound regulating gastric acid secretion and mediation of allergic reactions.

18. Dopamine Decarboxylation Is involved in the formation of dopamine from dopa. Dopamine is a neurotransmitter. It is also a precursor for the synthesis of biogenic amines such as norepinephrine and epinephrine.

19. 5-Hydroxytryptophan decarboxyalse: Catalyzes the conversion of 5-hydroxytryptophan to 5-hydroxytrptamine (serotonine)

20. Heme Biosynthesis δ-amino levulinic acid synthetase PLP is a cofactor for δ-aminolevulinic acid from glycline and succinylCoA.

21. Tryptophan metabolism Kynureninase PLP is required for the normal conversionl of tryptophan to niacin. PLP is a cofactor for the enzyme kynureninase that catalyzes the conversion of 3-hydroxykynurenine to 3-hydroxy anthranilate. Xanthurenicaciduria In pyridoxine deficiency, 3-hydroxykynurenine is metabolized by an laternative pathway leading to increased excretion of xanthurenic acid in urine (xanthurenicaciduria.

22. Xanthurenic acid

23. Glycogen metabolism Glyclogenphosphorylase PLP is a cofactor for glycogen phosphorylase. Glycogen phosphorylasecatlyzes the hydrolysis of glycogen to form glucose 1-phosphate. It is the rate limiting enzyme of glycogenolysis.

25. Trans-sulfuration Reaction Cystathionineβsynthase and cystathioninase. Transsulfuration reaction is involved in the formation of cysteine from methionine. PLPis a cofactor for cystathionineβsynthase and cystathioninase.

27. CO2 OxidaseDecarboxylase PLP CysteineCysteic acid Taurine Decarboxylase PLP Serine ethanol amine CO2 decarboxylase Histadine Histamine PLP

28. Sources and daily requirements Diatary Sources Rich sources of pyridoxine are whole grain cereals, organ meats, eggs and legumes. Daily Requirement Adult men daily requirement of pyridoxine fro adult men is about 2.5 mg/day. Adult women daily requirement of pyridoxine fro adult women is about 2.0 mg/day.

29. Pregnancy and lactation The daily requirement of pyridoxine for pregnant and lactating women is about 3 mg/day. Increased in alcoholism as acetaldehyde inhibits pyridoxalkinase

30. Deficiency Causes: Decreased dietary intake pyridoxine deficiency can occur with decreased intake of nutrients. Alcoholism alcoholism is one of the important cause for deficiency of pyridoxine. Imparied absorption-------; -diseases of small intestine can lead to malabsorption of nutrients including pyridoxine Antivitamins prolonged administration of drugs like isoniazid; pencillamine are associated with pyridoxine deficiency

31. Mainfestations Neurological disorders: Serotonin Epiniphrine Non epinephrine Decreased production GABA leading to neurological manifestations Decreased GABA causes convulsions mainly in childrens Deficiency

32. Clinical features • Hypochromicmicrocyticanaemia as it is required for synthesis of heam • Convulsions as it is required for synthesis of GABA a neurotrasmitter • Skin lesions like seborrheic dermatitis around mouth ;nose; eyes • Activities of all transeaminases is decreased as PLP IS REQUIRED as coenzyme for AST , ALT

33. Assay 1.Tryptophan over load test 2 gm orally tryptophan given More than 3mg of Xanthnuric acid in 24 hours urine Indicate deficiency 2. Methionine over load test Measurement HomocysteineCystathionine

34. IN pridoxine deficiency tryptophan is not converted to NAD ; AS PLP IS REQUIRED by the ENZYME -- KENURENINASE– so pellagra seen in B6 deficiency • THERE IS INCREASED EXCREATION OF XANTHENURIC ACID IN THE URINE

35. In pyridonxine deficiency there is increased excreation of homocysteine; as PLP is required for cystathionine beta synthase and cystathioninase. • Due to deficiency of pyridoxine Xanthurenic acid excreation is increased, as PLP is required for enzyme kynureninase.

36. In pyridonxine deficiency there is increased excreation of homocysteine; as PLP is required for cystathionine beta synthase and cystathioninase. • Due to deficiency of pyridoxine Xanthurenic acid excreation is increased, as PLP is required for enzyme kynureninase.

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