Water Soluble Vitamins PDF

Elliot Reed Biochemistry 5124 Contact: [email protected] Water Soluble Vitamins  Learning Objectives 1. Solubility of each Vitamin 2. Sources of each vitamin 3. Whether each vitamin is used as a coenzyme 4. Function of each vitamin 5. Diseases associated with each vitam...

Elliot Reed Biochemistry 5124 Contact: [email protected] Water Soluble Vitamins  Learning Objectives 1. Solubility of each Vitamin 2. Sources of each vitamin 3. Whether each vitamin is used as a coenzyme 4. Function of each vitamin 5. Diseases associated with each vitamin  Lipid and Water Soluble Vitamins Lipid Soluble Water Soluble Vitamin A Vitamin C Vitamin B12 Vitamin D Vitamin B1 Vitamin E Vitamin B2 Vitamin K Vitamin B6 Vitamin B9 Lipid Soluble vitamins are stored in fatty Water soluble vitamins are not tissue and the liver. They can accumulate in stored in the body and any unused the body over time. vitamin is primarily excreted in urine.  Vitamin B1 Thiamine Vitamin B1 is a water-soluble vitamin. Sources include pork, fish, legumes, and enriched grain products (cereal, bread, rice). Plays a key role in carbohydrate, branched-chain amino acid, and fatty acid metabolism  Conversion of Thiamine to TPP Thiamine alone is not biologically active and must be converted to thiamine pyrophosphate in the liver  Metabolism Pathways Requiring TPP https://lpi.oregonstate.edu/book /export/html/6721  Summary of Metabolism Requiring TPP TPP serves as a coenzyme for Pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, 2- oxoadipate dehydrogenase, and branched-chain α-ketoacid dehydrogenase (BCKDH). Products of these pathways all play a crucial role in energy production, through the citric acid cycle. TPP serves as a coenzyme for transketolase, a crucial enzyme for the pentose phosphate pathway (provides precursors for amino acid and nucleotide synthesis/ provides NADPH).  Thiamine Deficiency Thiamine deficiency is also referred to as beriberi. Beriberi can be categorized into three main groups Dry Beriberi- peripheral neuropathy. “burning feet syndrome”, abnormal reflexes, weakness/loss of sensation in arms and legs Wet (cardiac) Beriberi- tachycardia (fast heart rate), edema, and eventually congestive heart failure. Cerebral Beriberi- Wernicke’s disease- abnormal eye movement, loss of gait, and cognitive impairment. Korsakoff’s psychosis- dementia. Most notable in alcohol use disorder. Clinical connection: Patients taking diuretics are more likely to experience thiamine deficiency and may require additional supplementation.  Vitamin B2 Riboflavin Vitamin B2 is a water-soluble vitamin. Sources include lean meats, eggs, and liver (meaty organs) Riboflavin is a precursor to FAD (flavin adenine dinucleotide), which is a coenzyme for many biochemical pathways Pathways include electron transport, DNA repair, nucleotide biosynthesis, beta-oxidation of fatty acids, amino acid catabolism, as well as synthesis of other cofactors such as CoA and heme groups.  FAD synthesis from Riboflavin Flavin Adenine Dinucleotide Vitamin B2 Development of Novel Experimental Models to Study Flavoproteome Alterations in Human Neuromuscular Diseases: The Effect of Rf Therapy - Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/Chemical-structures-and-metabolic-conversion-of-Riboflavin-Rf- and-flavin-cofactors-in_fig1_343234875 [accessed 25 Sept 2024] Example of FAD Dependent Pathway  Vitamin B2 Diseases Since B2 is water-soluble, excess riboflavin is excreted quickly through urine. Too much B2 may cause bright yellow or orange urine. Deficiency may cause endocrine abnormalities Severe deficiency may cause degeneration of liver and nervous system.  Recap Questions What are the four lipid soluble vitamins? Select All That Apply: Thiamine pyrophosphate is a coenzyme for: A. Dehydrogenases B. Hydroxylases C. Transketolase D. Methionine Synthase T or F: After Vit. K is used as a coenzyme, it can be regenerated into its active form through two reduction steps.  Vitamin B6 Vitamin B6 is a water-soluble vitamin Found in chickpeas, fish, and beef liver It is an important coenzyme to many biochemical functions, such as amino acid metabolism, glycogen phosphorylation, and hormone-DNA binding termination. Vitamers of B6 There are 6 different compounds that have B6 activity. The most abundant and biologically active vitamer is pyridoxal phosphate (PLP). It is an important coenzyme to many biochemical functions, such as amino acid metabolism, glycogen phosphorylation, and hormone-DNA binding termination. PLP is a Coenzyme for Many Different Enzymes PLP serves as a coenzyme for many different amino acid DOPA DC- decarboxylase metabolic pathways GAD: Glutamate decarboxylase Pathways include dopamine synthesis from tyrosine and GABA synthesis from glutamate Enzymes are usually decarboxylases and aminotransferases PLP as a Coenzyme Examples  Vitamin B6 Related Diseases Excess vitamin B6 can cause neurotoxicity due to extended half life of metabolites. This is usually avoided by dosing weekly instead of daily. Vitamin B6 deficiency can cause microcytic anemia (smaller than normal red blood cells) Vitamin B12 Cobalamin Vitamin B12 is a water-soluble vitamin Vitamin B12 is obtained through the diet, with the main sources being beef liver, fish, mollusks, and nutritional yeast. Vitamin B12 is a coenzyme for two different enzymes, methionine synthase and L- methylmalonyl-CoA mutase. These enzymes are used in the conversion of homocysteine to methionine and succinyl CoA synthesis. Vitamin B12 Cobalamin Vitamin B12 is a Coenzyme for Methionine Synthase The final product of this pathway is S- adenosylmethionine, which is a universal methyl donor for many other pathways, including DNA synthesis Vitamin B12 is a coenzyme for L- methylmalonyl-CoA mutase  Vitamin B12 Associated Diseases Excess vitamin B12 can cause headache, nausea, and diarrhea. Vitamin B12 deficiency can cause: Pernicious Anemia- decrease in functional red blood cells Functional Folate deficiency Pernicious Anemia is often treated with large amounts of oral B12 supplements or a monthly injection. Vitamin B9 Folate Vitamin B9 is a water-soluble vitamin Foods rich with B9 are leafy greens, fortified grains, avocado and broccoli Folate is an important coenzyme for single carbon transfer reactions in nucleic acid synthesis (DNA/RNA) and amino acids catabolism and conversion of homocysteine to methionine Folate often donates/accepts methyl groups  Structures of B9 Active forms of folate are the tetrahydrofolates (THF)  Pathways involving Folate dUMP=deoxyuracil monophosphate dTMP=deoxythymidine monophosphate  Folate Deficiency Folate deficiency during pregnancy can cause severe complications due to its importance in fetal development of the central nervous system. These birth defects are called neural tubal defects. This includes spina bifida and anencephaly Folate deficiency in non-pregnant populations can cause: Megaloblastic anemia (abnormally large blood cells with abnormal nuclei) Elevated homocysteine levels (higher risk of stroke and heart disease)  Checkpoint Questions Which coenzyme is important for the decarboxylation of L-DOPA in the synthesis of dopamine? A. Vit. D B. TPP C. B12 D. PLP What vitamin is a coenzyme for the synthesis of succinyl CoA? A. B12 B. B9 C. B7 D. B2 Where does the methyl group in methylcobalamin come from? A. Methylmalonyl-CoA B. Serine C. Folate vitamer D. B12 vitamer  Vitamin C Ascorbic Acid Vitamin C is a water soluble vitamin Vitamin C comes from our diet, specifically fruits and vegetables Great sources of vitamin C include citrus fruits, strawberries, broccoli, and brussels sprouts. Vitamin C is important for many biological processes. Vitamin C serves as a coenzyme for multiple biochemical pathways, aids in iron absorption, and similarly to Vitamin E, serves and an antioxidant Its importance to many biological pathways is due to its property as a reducing agent  Vitamin C Ascorbic Acid Image Source Doseděl M, Jirkovský E, Macáková K, Krčmová LK, Javorská L, Pourová J, Mercolini L, Remião F, Nováková L, Mladěnka P, On Behalf Of The Oemonom. Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination. Nutrients. 2021 Feb 13;13(2):615. doi: 10.3390/nu13020615. PMID: 33668681; PMCID: PMC7918462.  Vitamin C as an Antioxidant Vitamin C acts as an antioxidant. It is an essential molecule for the vitamin E cycle and alleviates the vitamin E free radical  Vitamin C in Norepinephrine Synthesis Summary: Vitamin C reduces the Copper atoms of the enzyme DBH (dopamine beta hydroxylase) and in turn, is oxidized.  Vitamin C as a Coenzyme for Iron Dependent Hydroxylases All iron dependent hydroxylases have similar mechanisms Iron hydroxylases are essential for many important biological pathways including collagen synthesis (ex. to the left) Vitamin C acts as a coenzyme for iron hydroxylases. Vitamin C reduces iron and is oxidized, which similar in norepinephrine synthesis The hydroxylation of proline is important for collagen synthesis. Hydroxyproline plays a crucial role in stabilization of collagen. Zhang, Zhenyu & Liu, Pengfu & Su, Weike & Zhang, Huawei & Xu, Wenqian & Chu, Xiaohe. (2021). Metabolic engineering strategy for synthetizing trans-4-hydroxy-L-proline in microorganisms. Microbial Cell Factories. 20. 10.1186/s12934-021-01579-2. Vitamin C as a Coenzyme for Iron Dependent Hydroxylases Hydrogen bonding occurs between hydroxylated amino acids from adjacent collagen strands and increases structural integrity Created with BioRender.com  Vitamin C surplus: Excess iron absorption GI upset Vitamin C associated Diseases Vitamin C deficiency: Scurvy Weakness, fatigue, anemia, reopening of wounds Impaired collagen synthesis  Checkpoint Questions Which of the following is NOT a function of Vitamin C? A. Hydroxylation of Proline B. Hydroxylation of Dopamine C. Protection from ROS D. Decarboxylation of L-DOPA What property of Vitamin C is important for its role as both an antioxidant and coenzyme? A. It's an oxidizing agent B. It's a reducing agent C. It's hydrophillic D. It's ring structure