Vitamin B6 Metabolism Nishita Mohan BBS – G1

Index What is Vitamin B6? Discovery Role in Metabolism Deficiency Treatment Future directions

What is Vitamin B6? Vitamin B6 is a water-soluble vitamin that naturally exists in three main forms: pyridoxine (PN), pyridoxal (PL), and pyridoxamine (PM), n collectively termed “pyridoxine” The active form of vitamin B6- pyridoxal 5'-phosphate(PLP) serves as a coenzyme in many enzyme reactions in amino acid, glucose, and lipid metabolism Pyridoxamine and pyridoxal in dilute solutions are labile compounds which are rapidly destroyed on exposure to air, heat, or light. B6 originally present in foods can be lost in processing: prolonged heating, cooking, sterilization and freezing.

The vitamers

Discovery of Vitamin B6 1930s: Rudolf Peters and the curious case of rat acrodynia

Discovery of Vitamin B6 1930s: Rudolf Peters and the curious case of rat acrodynia 1934: Paul György showed that the factor which cured 'rat acrodynia' was vitamin B(6)

Discovery of Vitamin B6 1930s: Rudolf Peters and the curious case of rat acrodynia 1934: Paul György showed that the factor which cured 'rat acrodynia' was vitamin B(6) Richard Kuhn and his associates independently showed that vitamin B(6) was a pyridine derivative, 3- hydroxy-4,5-dihydroxy- methyl-2-methyl-pyridine.

Sources of Vitamin B6

Absorption of vitamin B6 Passive diffusion of ‘free forms’ in the jejunum and iluem Membrane bound alkaline phosphatases required for absorption in the duodenum

Absorption of vitamin B6 Passive diffusion of ‘free forms’ in the jejunum and iluem Membrane bound alkaline phosphatases required for absorption in the duodenum Converted into the active form, pyridoxal-5- phosphate (PLP) by Pyridoxal Kinase (PDXK)

Absorption of vitamin B6 Passive diffusion of ‘free forms’ in the jejunum and iluem Membrane bound alkaline phosphatases required for absorption in the duodenum Converted into the active form, pyridoxal-5- phosphate (PLP) by Pyridoxal Kinase (PDXK) PLP released into the blood stream and travels to tissues bound to Albumin

Storage of Vitamin B6 Majority of the body’s vitamin B6 is stored in the muscle Small amount of PLP retained High turnover! A large amount is excreted out

Should I really study this vitamin?! Amino acid biosynthesis & degradation Neurotransmitte r biosynthesis &degradation Sphingolipid biosynthesis Folate biosynthesis Heme biosynthesis Glycogen metabolism

Role in Glycogen Metabolism ???? Dr. Michel’s lecture

Role in Glucose Metabolism Dr. Michel’s lecture

Role in Glucose Metabolism Proton donor Proton Acceptor NOTE: Phosphate group of PLP plays the important role!!

Role in amino acid metabolism Imine formation Inwha’s talk Aldehyde group plays the key role!! Function: Electron sink

Role in amino acid metabolism Fate?? Pyruvate

Role in amino acid metabolism NOTICE HOW THE CATALYSIS MECHANISMS ARE COMPLETELY DIFFERENT!!

Neurotransmitter biosynthesis Dan, Songlei’s talks

Clinical correlation Isolated vitamin B6 deficiency is uncommon; associated with low concentrations of other B group vitamins –B12 & folate – microcytic anemia – electroencephalographic abnormalities – dermatitis and glossitis (swollen tongue) – depression and confusion – weakened immune function – In infants, vitamin B6 deficiency causes irritability, abnormally acute hearing, and convulsive seizures

Risk factors Impaired renal function Autoimmune disorders- Rheumatoid Arthritis Malabsorptive autoimmune disorders- celiac disease, Crohn's disease, ulcerative colitis, inflammatory bowel disease Alcohol dependence

Future directions Potential role in lowering the risk of cardiovascular diseases Vitamin B6 and the immune system Role in the reduction ofPMS symptoms Interactions with different medication and nutrients

Summary Vitamin B6 is an important co-factor required in several metabolic pathways It is readily absorbed in the small intestine and the uptake is mediated by passive diffusion It has several interconvertible forms but the active form is PLP Enables the breakdown of glycogen to glucose, amino acid metabolism, serotonin production Deficiency of vitamin b6 is associated with certain groups which have high risk factors

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