Niacin B3 Niacin B3 deficiency is called Pellagra It causes rough skin or rash The sun can cause castle s collar We do not see much of this in the United States B vitamins are mostly found in animal products Grains are now enriched with this but do not provide the complete amount Food sources include fish such as tuna and halibut meat such as chicken beef turkey and pork and enriched cereals and bread products So if you are milling your own flour you are not getting Niacin We make Niacin in our body from Tryptophan but it takes 60mg of Tryptophan to make 1 mg of Niacin This is maybe just enough to keep us out of deficiency but does not meet our needs entirely Forms Two forms of the vitamin are Nicotinic acid Niacin and Nicotinamide Niacinamide big Vitamins transport form will always be transported in blood in the smallest form and then once difference here is that the latter has an amine group The two Co Enzyme forms are NAD and NADP in the cell it can be converted to a Co Enzyme utilization form Co Enzymes such as NAD or NADP are always large compounds Digestion and absorption We eat it in all forms We eat it in plant form as in Nicotinic acid animal form from free Nicotinamide and Co Enzyme forms of NAD and NADP How are we going to transport this big Co Enzyme form into the enterocyte We will turn it into the vitamin form So NAD and NADP are hydrolyzed in intestine to free Nicotinamide also known as Niacinamide This is done by Glycohydrolase enzyme This enzyme is in your intestine only So if you consume it in the Co Enzyme form you must convert it to the vitamin form to get it through the membrane of the enterocyte Your small intestines are lined with enterocytes which are attached to the portal blood them This then goes back to system on the other side of your intestine is where all your liver So in the lumen of your digestive enzymes function including Glycohydrolase vitamin form This can send which changes Co Enzyme into where it can use it or it can vitamin to the enterocyte be sent to the blood where it will then go to the liver The the rest of the body liver can use it or it can go to Acid are absorbed in the Nicotinamide and Nicotinic small intestine This is another concept that you will see in B vitamins at low concentrations you have sodium dep Facilitated diffusion with carriers that help vitamins enter the enterocyte The pharmacological or large doses such as supplementation use passive diffusion because you have more vitamins there than there are receptors Niacinamide is transported in the blood to tissues and then that Niacinamide or Nicotinamide serve as precursors to your Co enzymes of NAD and NADP in cells Vitamin form Co enzyme form NAD and NADP are required by 200 enzymes NAD is used for energy and accepts hydrogens and donates them at the ETC Using NAD you are usually creating energy NADP is a reducing agent for synthesis pathways So although these Co enzymes have similar structures they have very different functions NAD Co enzyme for Dehydrogenases Sometimes it is FAD but most of the time it will be NAD and an example will be later 2 NAD are involved in glycolysis with Glyceraldehyde 3 phosphate dehydrogenase enzyme which converts Glyceraldehyde 3 phosphate to 1 3 bisphosphoglycerate These next ones are all energy producing pathways We see NAD used in Pyruvate to Acetyl CoA with pyruvate dehydrogenase Krebs cycle reactions involving Isocitrate malate and ketoglutarate dehydrogenase exception is succinate dehydrogenase because that uses riboflavin FAD in oxidation with hydroxyacyl CoA dehydrogenase and lastly in oxidation of ethanol with alcohol and acetaldehyde dehydrogenase Then we take the NADH and it moves through either the aspartate or malate shuttle It then Energy production via ETC Each NADH produces 3 ATP Our proton pumps are 1 3 4 and ATP moves into mitochondria and drops off H s off at ETC 1 NADH for this class produces 3 ATP synthase Only complex name she stated was complex I NADH dehydrogenase complex A good website for an animation is http vcell ndsu nodak edu animations etc first htm DNA NAD donates ADP ribose and attaches it to a protein to form cyclic ADP ribose Cyclic ADP ribose plays a part in DNA repair replication and cell differentiation So NAD is important for energy and in DNA for the reasons just stated NADP is formed into NADPH in the HMP Shunt pentose phosphate pathway NADPH is then used in the following reactions FA synthesis add 2 C to Acetyl CoA desaturation of FA removing double bonds by adding H s Cholesterol synthesis Folate metabolism and alcohol metabolism MEOS MEOS is alternative to ADH if that enzyme is saturated How do we know if somebody has enough Niacin You can look for N methyl Niacinamide NMN in urine or check blood levels If vitamins are not absorbed they leave in fecal matter If they are absorbed they can either go to blood and be utilized in tissues or cannot be utilized and excreted in urine even though it was absorbed Deficiency Those at risk are people who take medications such as Isoniazid which decreases Niacin synthesis It is a drug for Tuberculosis People with malabsorptive disorders are people who cannot absorb it and it leaves in fecal matter This includes IBD Crohns and some cancers Hartnup Disease affects A A synthesis and utilization So if we have low Tryptophan A A it can affect Niacin Lastly excessive alcohol intake can inflame bowels It will also increase vitamin utilization and excretion through diuresis Primary deficiencies are caused by not consuming vitamin Secondary deficiencies are caused by consuming but problems in other areas such as utilization and absorption Deficiency can cause Pellagra with symptoms of dermatitis dementia diarrhea and death known as 4 D s In the U S the government mandates the fortification of vitamins in our foods Pellagra shows scaly sores mental changes and inflamed mucosal membranes Toxicity Those taking pharmacological doses of Nicotinic acid by Niacor or Advicor Niacor is a Niacin based medication Advicor is Nicotinic not Nicotinamide With the amide attached it changes the ability for the attachment of receptors so it is Nicotinic Acid for that reason Medication is used to treat hypercholesterolemia It causes HDL s to go up and LDL s to decrease High doses may cause vasodilation flushing itching and headaches GI discomfort heartburn nausea Hepatic toxicity liver failure jaundice and Glucose intolerance Slow release or non flushing is typically Nicotinamide It is
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