Lec 3 Vitamins PDF

Lecture 3 Vitamin B5 [Pantothenic acid] It is a peptide substance consists of pantoic acid [α,γ dihydroxy-β-dimethyl butyric acid] connected in amide linkage to β-alanine. It can be present as the ca-salt or the alcohol form "Pantothenol" pantothenic acid [Vit. B5]is a part of coenzyme...

Lecture 3 Vitamin B5 [Pantothenic acid] It is a peptide substance consists of pantoic acid [α,γ dihydroxy-β-dimethyl butyric acid] connected in amide linkage to β-alanine. It can be present as the ca-salt or the alcohol form "Pantothenol" pantothenic acid [Vit. B5]is a part of coenzyme A or ACP [How]? ⇒pantothenate Kinase phosphorylates Pantothenic acid,using ATP as a phosphate donor, forming 4_ phosphoPantothenic acid. ⇒4-phosphoPantothenic acid condenses with cysteine, the carboxyl group is removed, Leaving thioethanolamine ∴Thioethanolamine bound to 4-Phosphopantothenic acid to form 4-phosphopantetheine. *4-phosphopantetheine may be used to form coenzyme A or ACP [acyl carrier protein] A)Coenzyme A [structure-function- relationship]:- The SH grop.[Thiol group]of coenzyme A forms its active center, this is why the Coenzyme is abbreviated [COA-SH] The acyl-racdicals [R-CO.]of many carboxylic acids [R-COOH] get attached in high energy thioester Linkage forming Acyl-COA ( R-CO ~ SCOA) [ R-COOH + COA-SH → R-CO ~ SCOA ]  The acids that may get attached to coenzyme A during metabolic reactions include the following:- ①Fatty acids :- Fatty acids react with coenzyme A, forming fatty acyl COA, which is important for the oxidation and formation or elongation of fatty acids. ② Acetic acids:- Acetic acid connected to coenzyme A- forming acetyl COA or active acetate, which is important for the oxidation of acetic acid or pyruvic acid throughT-C-A cycle as well as formation of fatty acids, steriods formation , and Ketone bodies Formation. ③ Succinic acid:- succinic acid connected to coenzyme A forms Succinyl COA an intermediate in the T-C-A cycle,important for heme synthesis, Ketolysis & detoxication (B) Acyl carrier protein [ACP]:- ACP is part of enzyme fatty acid synthase responsible for fatty acid synthesis 4-Phosphopantetheine is esterified, through phosphate, to the alcohol group of a serine residue in the polypeptide chain of protein to Form ACP. ACP acts as carrier of acyl radicals of fatty acids during the reactions of fatty acid synthesis The acyl radicals are connected in high-energy thioester linkage to the -SH gp.of 4-phosphopantetheine. Natural sources:- Animal sources:- Livers, kidney and heart Milk and Milk products[cheese, yogurt and butter] plant sources:- cereals Honey and Molasses Yeast * Required Daily Amount: - _ 4-Years and over to 10 mg/day _ Less than 4 years 5 mg / day _ Infants 3 mg/day * Deficiency:- Rare to occur: No specific manifestations for Pantothenic acid deficiency were reported in men. This is probably due to widespread distribution in natural foods ***when Occur it Lead to [paresthesias] (is a sensation of tingling, pricking or numbness of a person's skin ) Uses:- Treat and prevent deficiency state. supplements in cases of inadequate diet It is described for:- _ Diabetic neuropathy , Arthritis Uses of dexpanthenol:- Topically used for Burning , Itching , Irritation.  Vitamin B6 [Pyridoxine ] pyridoxine, also known as pyridoxol ,is 2- methyl- 3-hydroxy 4,5 bis [ hydroxy methyl] pyridine It is mainly produced by plants There are four other physiologically active forms of vitamin. B6 are found in natural food obtained from animals. **AII forms of vit.B6 are absorbed from the intestines after removal of phosphate. ⇒ pyridoxine is oxidized, and pyridoxamine is deaminated,forming pyridoxal. ⇒ Pyridoxal Kinase, adds a phosphate from ATP to Pyridoxal, forming pyridoxal phosphate (PLP)which is the major form of pyridoxine in the blood plasma and the active form in tissues. **Further Oxidation of pyridoxal produces pyridoxic acid which is the principal excretory product of vit.B6 in the urine. * Natural sources:- vitamin B6 is found in: cereals, beans, meat, liver, fish , Yeast, Nuts and some fruits as banana and potatoes. It is also produced by bacterial flora in the colon *Role of vitamin B6 pyridoxal phosphate is the active form of pyridoxine in tissues, It is important for. A)Metabolism of amino acids→ involved more than 100 enzymes such as ① Transaminases ② Decarboxylases of amino acids ③ Dehydratases of amino acids ④ cysteine Desulfhydrase ⑤ Transsulfurases [Transulfhydrases ] ⑥S -Aminolevulinate synthase ⑦ Kynureninase B)Glycogenolysis -vitamin B6 also helps maintain blood glucose within a normal range. When caloric intake is low, vit B6 help to convert the stored carbohydrate or other nutrients to glucose to maintain normal blood sugary levels [How?] -The aldehyde group. of plp forms a schiff base With the Ԑ-amino group of-lysine residues in the polypeptide chain of the enzyme glycogen phosphorylase. *About 75 % of the total body pyridoxine are found in muscle in this form *Glycogen phosphorylase catalyzes the breakdown of glycogen into glucose -1-phosphate. Note:- -PLP is a Stabilizer of his enzyme, but remains unchanged during the RX.,i.e. [does not function as a coenzyme]. D) The nervous system and the immune system need Vit.B6 to function. E ) It is also need for the conversion of tryptophan [ amino acid] to Niacin [vit. B3] C) It is also essential for red-blood cell metabolism. A) Metabolism of amino acid:- _ The aldehyde group of pyridoxal phosphate [pLp] can from a Schiff-base with the amino group of an α- amino acid. So this facilitate changes in all the bonds surronding the α- carbon atom. Thus plp is a coenzyme in amino acid metabolism. ① Transaminases:- [ α- amino acid(old) + α- Keto acid (old) α- amino acid (new) + α-Keto acid new (new)] -These catalyze the transfer of an amino group from an α- amino acid to an α- Keto acid, forming a new- α-Keto acid & a new α-amino acid, respectively [by helping from plp] -The RX. is reversibly - The most 2 famous transaminases are widely distributed in tissues, alanine transaminase or [ALT] or known as glutamate pyruvate transaminase[GPT] and Aspartate transaminase[AST] or glutamate oxaloacetate transaminase [GOT ] ②Decarboxylases of amino acids :- * There are enzymes for the decarboxylation of histidine , tyrosine, 5,4 dihydroxy phenyl alanine( dopa) and 5- hydroxytryptophan to the corresponding primary amines , histamine, tyramine, dopamine and 5-hydroxytryptamine [serotonin], respectively * L-glutamate-α-decarboxylase:- converts glutamic acid to γ-amino butric acid [GABA] * GABA: An important regulator Of neural activity it decreases the postsynaptic potential, inhibiting synaptic transmission. ③ Dehydrates of amino acids:- -These are enzymes important in the deamination of hydroxyl amino acids [ex. serine, threonine] ④ Cysteine Desulfhydrase:- - This enzyme is important in the deamination of the Sulfer amino acid cysteine. ⑤Transulfurases[Transulfhydrases]:- - The enzymes cystathionine synthase and cystathionase are involved in the transfers of-SH group from homocysteine to serine , forming homoserine and cysteine,respectively ⑥δ-Aminolevulinate syntnetase:- -This enzyme catalyzes the condensation of glycine [a.a.] with Succinyl COA to form S-aminolevulinic acid [S-AIA] the precursor of heme. ⑦ Kynureninase:need PIP This enzyme catalyzes the conversion of 3- hydroxykynurenine to 3- hydroxyanthranilic acid, which important in the formation of niacin from tryptophan In pyridoxine deficiency , 3-hydroxykynurenine is converted to xanthurenic acid Which is excreted in the urine in large amounts. note :[Help in diagnosis for plp deficiency [in lab] ]? Required daily amount:- Males 15 years and older 2.0 mg/day Female 19 years and older 1.6mg / day pregnancy [2.2mg. )/ day Lactation [2.1mg] / day. Causes of deficiency:- - Individuals with a Poor quality diet or an inadequate B6-intake -Deficiency of pyridoxine may occur during pregnancy, long term use of oral contraceptives and in alcoholics. *In these cases increased requirement for pyridoxine more than for most of the B-vitamins due to [for example],In alcoholics, acetaldehyde, the product of oxidation of ethanol displaces pyridoxal phosphate From its enzymes, thus helping its excretion. Deficiency may also occur in infants nursed by Mothers Who have long been using oral contraceptives In older people Asthmatic children:treated with theophylline because it decrease body ability to store Vitamin B6. Deficiency of pyridoxine occurs in tubercIous patients treated with isoniazid [isonicotinic acid hydrazide INH] a drug that interferes with the action of Pyridoxal phosphate by combining with aldeheydic group * signs of vitamin B6 deficiency include :- skin:- Dermatitis [Skin inflammation ] stomach: Stomatitis [stomach inflammation ] tongue:- Glossitis [inflammation or infection of the tongue] *Inflammation of the mucous lining of any of structures in the mouth. Neurological abnormalities:- Depression, confusion →due to decrease levels of GABA in CNS [especially in patients treated with isoniazid, cycloserine or penicillamine.] Vitamin B6 deficiency also can cause anemia ,Known by Sideroblastic anemia → [accumulation of iron in RBCs] Alimentary tract manifestations:- These include anorexia, nausea and vomiting They are particulary observed in pregnant women * Uses:- Treatment and preventation of deficiency. For people are high risk of deficiency can also described in: *Acne *kidneys stones *premenstrual syndromes Improve some C.N.S conditions * Side effects or toxicity of pyridoxine:- Neurologic symptoms [neuropathy] have been observed at intakes of greater than 2g/day. can result in nerve damage to the arms and legs substantial improvement , but not complete recovery, occurs when the vitamin is discontinued. * Interaction:- * Some drugs increase the excretion of vitamin B6 by the body as: chloromphenical. oral-contraceptive Isoniazide L-Dopa Cycloserine and penicillamine → couples with the adehydic group of pyridoxal phosphate, blocking its functions.