Vitamin B's (8)

Draw and write Chemical Structures on paper.

Vitamin B1 - Thiamin	Information	Additional Information
Functional Group	Alkyl group (site of phosphorylation)	Pyrimidine ring, thiazole, alkyl group
Active Form(s)	Thiamin Diphosphate (TDP) Thiamine pyrophosphate (TPP)	90% TPP is found in RBC (10% is TMP) 80% total thiamin exists as TPP
Dietary Food	Grain products (33%) Animal (25%) Fortified flour	Grains - 95% as free thiamin Meats - 95% TDP & TMP
Absorption	Jejunum Via ThTR1	And ileum
Transporters & Receptors	Active transport: Thiamin transporter-1 (ThTR1) - absorption Thiamin transporter-2 (ThTR2) - uptake (to cells and brain Passive diffusion Reduced folate carrier 1 (RCF1) - transports TMP TPP Carrier (SLC25A19)	Alcohol inhibits ThTR1 and ThTR2 Found in muscle, heart, liver, kidney, pancreas, brain High thiamin intake can bypass ThTR1 SLC19A3 codes for ThTR2
Reabsorption	Proximal tubule cell via ThTR1, ThTR2, and RCF1 (95% gets reabsorbed)
Coenzyme Functions	Dehydrogenase Reactions Pyruvate Dehydrogenase (E1) - TPP is a coenzyme for decarboxylating pyruvate a-Ketoglutarate Dehydrogenase - succinyl-CoA oxidation for energy synthesis Branched-Chain a-keto acid Dehydrogenase - metabolizing BCAA for muscle energy Transketolase Reactions Pentose Phosphate Pathway (Shunt Pathway) - synthesizes NADPH for biosynthetic pathways, detoxification, reduced glutathione, DNA and RNA synthesis Nucleophilic Attack - energy synthesis
Other Functions	Nervous System Neurological functions require high levels of metabolic demand (TPP is needed for ATP synthesis) Red Blood Cell RBC has high PPP activity and NADPH synthesis for glutathione defense	Electric and chemical nerve stimulation releases thiamin & TMP NAPDH is important for DNA and RNA
Related Pathways	Pentose Phosphate Pathway (Shunt Pathway)
Assessment & Status	RBC lysates - expensive & most sensitive Erythrocyte Transketolase Activity (ETKA) - functional assay for thiamin status	Reference Range: 2.5-7.5ug/dL Urine Deficiency: <40ug/day
Deficiencies	Dry (neuritic) Beriberi - paraesthesia, peripheral neuropathy, limited knee/ankle jerk, ataxia Wet (cardiac, edematous) Beriberi - heart complications (polished carb intake) Fulminant (Shoshin, pernicious) Beriberi - heart failure, peripheral edema, lactic acidosis, typically in Japanese Wernicke-Korsakoff Syndrome - brain lessions, ocular nerve paralysis, ataxia, psychosis, memory loss	Alzheimer’s and Parkinson’s disease are associated with thiamin deficiency
Risk Factors for Deficiencies	polished rice, wheat thiaminase-rich foods (raw fish) anti-thiamin factors, tannic acid (tea, coffee) alcohol thiamin disulfide (poorly absorbed)
Mutations	SLC19A3 - gene coding for ThTR2 Transketolase TKT gene - inability to synthesize NADPH

Vitamin B2 - Riboflavin	Information	Additional Information
Functional Group	Flavin (Isoalloxazine)	Flavin, ribitol sugar, isoalloxazine ring Flavin + UV light = lumiflavin and lumichrome
Active Form(s)	Flavin mononucleotide (FMN) Flavin adenine dinucleotide (FAD)	Via Riboflavin Kinase Via FAD synthetase
Dietary Food	Meats, whole grains, green leafy vegetables Bioavailability - 40-60%	95% FMN & FAD bound to proteins
Absorption	Duodenum Via RFT1 and RFT2	60-95% FAD form in the liver
Transporters & Receptors	Riboflavin transporter-1 (RFT1) - absorption RFT2 - intracellular transport RFT3 - placenta transport for brain uptake SLC52A1 - gene code for RFT1 SLC52A2 - gene code for RFT2 SLC52A3 - gene code for RFT3 Riboflavin-Binding Proteins (RfBPs) - transfer of B2 to reproductive and maternal tissues	RFT increases as dietary riboflavin increases
Reabsorption	Renal urinary ducts
Coenzyme Functions	Redox Reactions Flavoenzymes Glutathione Reductase - NADPH and FAD are needed for regeneration of reduced glutathione, important for RBC Glutathione recycling Dehydrogenase Reactions NADH Dehydrogenase - FMN transfers electrons from NADH Succinate Dehydrogenase (Complex II) - FAD (has enough energy to) oxidizes succinate to produce ATP Pyruvate Dehydrogenase (E3) - FAD is a cofactor for electron transfer a-Ketoglutarate Dehydrogenase - FAD converts pyruvate to acetyl-CoA for TCA cycle	FAD is used more as a coenzyme Important for ATP synthesis
Other Functions	ATP Synthesis Krebs Cycle (TCA Cycle) Enzymes Electron Transport Chain (ETC) Complexes Iron Metabolism Needed for iron absorption and metabolism (keeps iron in reduced state) Vitamin Metabolism Niacin (tryptophan conversion to NAD), VB6 activation (PLP to PL), Folate recycling (FAD needed for MTHFR)
Related Pathways	Kynurenine Pathway - FAD needed to convert tryptophan to NAD+ Folate and Methionine Cycle (FAD needed for functioning MTHFR) Krebs Cycle / TCA Cycle - ATP synthesis Electron Transport Chain - ATP synthesis
Assessment & Status	Erythrocyte Glutathione Reductase Activity Coefficient (eGRAC) - functional assay, measures FAD Erythrocyte Riboflavin Content Urinary Riboflavin Excretion	Low-High Risk <1.15 >1.25
Deficiencies	Cheilosis / Angular Stomatitis - sores on the corners of mouth, lips Glossitis - inflamed tongue Anemia Demyelinating peripheral neuropathy
Risk Factors for Deficiencies	Impaired erythropoiesis and loss of ferric reductase activity Secondary deficiency with other b vitamins
Mutations	SLC52A3 mutation - causes impaired riboflavin transport across the placenta

Vitamin B3 - Niacin	Information	Additional Information
Functional Group	Nicotinic Acid Nicotinamide Nicotinamide Riboside (NR)	Pyridine ring, carboxylic acid or amine group, ribose sugar (NR)
Active Form(s)	Tryptophan → NAD+	Tryptophan can convert to NAD+ Niacin is the precursor to tryptophan
Dietary Food	Animal - NAD+ Plants - Nicotinic Acid Poultry, red meat, eggs - Tryptophan Microbiome of colon - Niacin	60mg tryptophan = 1mg niacin = 1mg niacin equivalent Bioavailability: 30%
Absorption	Duodenum	NAD+ cleaves, NAM is made
Transporters & Receptors	No specific niacin transporter Carrier-medicated facilitated diffusion B0AT10 - renal & intestinal uptake SLC5A8 - intestinal absorption, renal reabsorption	NR, NMN, NAD+ converts into Nicotinamide (Nam) in the duodenum. Nam goes through cell uptake via Salvage pathway and produces NAD+ 70% as NADPH in RBC 30% free niacin bound to albumin
Reabsorption	B0AT10 - renal reabsorption SLC5A8 - renal reabsorption
Coenzyme Functions	Redox Reactions NAD+ & NADH as electron carriers (H-) in oxidation and reduction reactions Dehydrogenase Reactions Pentose Phosphate Pathway (E3) - NAD+ used as a coenzyme to transfer electrons	Oxidation (NAD+) Reduction (NADH)
Other Functions	NAD+ Synthesis De-novo Pathway (Kynurenine pathway) - NAD+ from tryptophan (B6 & B2 needed) Preiss-Handler Pathway - NAD+ from dietary nicotinic acid NAD+ Salvage Pathway - NAD+ from nicotinamide (NAM) recycling (from diet) by reversing NAD cleave DNA Single Strand Breaks (SSB) PARP1 uses NAD+ as a substrate (for ADP-ribose) PARP1 detects SSB and slows down DNA SSB repair with ADP-ribose attached Gene Expression (Transcription) Silent Mating Type Information Regulation 2 Homolog 1 (SIRT1) - NAD needed to remove acetyl groups for SIRT1 to deacetylase Hyperlipidemia Treatment Nicotinic acid can suppress lipolysis, ApoB, VLDL Increases HDL and ApoA1	NAD+ Salvage Pathway is linked to the excretion pathway Too much PARP1 can lead to necrosis/cancer but inhibited PARP1 can lead to apoptosis (inability to fix SSB, better than necrosis) SIRT1 suppress gene expression during fasted state, good for longevity, increased protein diversity, and efficient gene repair and cell survival (ATP generation)
Related Pathways	Kynurenine Pathway	Disrupts Kynurenine pathway - accumulation of xanthurenic acid
Assessment & Status	N-methylnicotinamide in urine levels Niacin urine excretion	Low to high >1.6mg <0.5mg
Deficiencies	Flushing - vasodilation of prostaglandin D2 (high doses of niacin only) Itching Severe GI discomfort Hyperuricemia - gout Pellagra (4 D’s - dermatitis, diarrhea, delirium, death) Casal collar Skin lesions (GI tract too) Neurological symptoms	Non-melanoma skin cancers - caused by exposure of UV radiation (reduced with nicotinamide supplementation) Treatment - niacin supplementation can reverse skin aberrations (pellagra)
Risk Factors for Deficiencies
Mutations	Hartnup Disease Mutation in SLC6A19 - gene that codes for B0AT1 (intestinal and renal absorption of tryptophan)	Will show high levels of amino acids in the urine, pellagra rash, neurological changes

Vitamin B5 - Pantothenic Acid	Information	Additional Information
Functional Group	Secondary alcohol, a carboxylic acid, and a secondary amide	b-alanine, pantoic acid
Active Form(s)	Coenzyme A (CoA) Acyl Carrier Protein (ACP)	PANK catalyzes CoA
Dietary Food	High in meat liver, heart, brain, royal jelly, mushrooms Egg yolk, milk, yogurt, legumes, whole grains, gut bacteria Bioavailability - 40-60%	85% Coenzyme A & Acyl-CoA in dietary PA 15% 4PTH bound to ACP in dietary PA
Absorption	Jejunum 4PTH is dephosphorylated from CoA and ACP to turn to PA (to cross brush boarder) CoA synthesis occurs in the liver	Diphosphatase & phosphatase turns CoA into 4PTH Proteases turns ACP to 4PTH Phosphatase & pnathethinase turns 4PTH to pantothenic acid
Transporters & Receptors	Active Transport Sodium-dependent multivitamin transporter (SMVT) Passive Diffusion A pharmacological levels Recycling Pantothenic Kinase II (PANKII) - phosphorylates PA to 4PTH and CoA (CoA gets recycled)	SMVT also transports biotin and lipoic acid SMVT mRNA inhibited by biotin, pantothenic acid, lipoic acid 90% PA converts to CoA, 90% CoA in mitochondria Heart - greatest concentrations of CoA
Reabsorption	Proximal convoluted tubule via SMVT High PA - excretes free PA and 4PTH
Coenzyme Functions	Acyl Transfers Reactions (Acetylations) Makes acetyl-CoA Alcohols, amines, AA N-terminal acetylation, histone acetylation Anabolic Reductive Reactions De novo synthesis of FAs via Malonyl-CoA Synthesis of sterols Production of acetoacetate - ketone body Catabolic Oxidative Reactions Activation of Fatty Acid Carnitine b-oxidation Oxidation of pyruvate to Acetyl-CoA Oxidation of a-ketoglutarae to Succinyl-CoA Oxidation of BCAA and a-keto skeletons Lysine Acetyl-CoA (from CoA acyl transfer) - Lysine is acetylated by Acetyl-CoA to create acetyl lysine for chromatin structure, metabolic activity, protein stability, gene expression Gene Transcription HAT catalyzes acetylation that neutralizes histones for better gene transcription	Low glucose levels during the fasted state causes the use of acetyl-CoA for fatty acid oxidation, in the fed state, this reaction will shift to fatty acid synthesis with ACP
Other Functions	Fatty Acid Oxidation (CoA) - CoA is needed for ASC to turn FA into Fatty acyl-CoA (this will enter the carnitine shuttle for ATP) De novo Fatty Acid Synthesis (ACP) - after FA oxidation, ACP will be a tether in the fatty acid synthase (FAS) complex Glycolysis Pentose Phosphate Pathway (E2) - CoA acetylates to Acetyl-CoA	ACP attaches to Malonyl-CoA, allowing it to grow a FA chain Used in skin care products (hygroscopic ability)
Related Pathways	Carnitine Shuttle (FA oxidation) - Fatty acyl-CoA enters the outer mitochondria with CPT1, turning into acylcarnitines, this can now enter the inner mitochondria membrane and turn back into fatty acyl-CoA (used for ATP)
Assessment & Status	Blood levels (not a good indicator) Urine extraction - functional assay	Ref BL - 1.6-2.7 Ref Urine - 2.5mg
Deficiencies	Burning feet syndrome - headache, fatigue, fatty liver, intestinal disturbances, numbness, tingling in hands and feet	Treatment - PA supplementation
Risk Factors for Deficiencies	PA deficiency is rare, tissues conserve PA, ubiquitous in food
Mutations	PANK2 Mutation - decreases CoA, increases cysteine, causes sulfur and iron to accumulate in the brain

Vitamin B6 - Pyrimidine	Information	Additional Information
Functional Group	Aldehyde group, phosphate group	Pyridine ring
Active Form(s)	Pyridoxine PN (alcohol), pyridoxal PL (aldehyde), pyridoxamine PM (amine)	Pn → PMP → PLP PL → PLP PM → PMP → PLP
Dietary Food	Animal foods (PL, PLP, PMP), plant tissues (PN) Bioavailability- 75%
Absorption	Jejunum
Transporters & Receptors	Protein-mediated transpoter (passive diffusion) Alkaline phosphate (APL) - dephosohorylates Vb6 into free forms B6-specific kinases - phosphorlyates B6 to active forms FMN oxidase - oxidized PMP and PNP to PLP	PLP is 75% found in muscle
Reabsorption
Coenzyme Functions	Schiff-Based Reactions (Transamination) Decarboxylation - GABA synthesis, serotonin synthesis, dopamine synthesis Glycogen Phosphorylase - the schiff base allows GP to catalyze glycoeolysis One Carbon Metabolism Transsulfuration Pathway - homocysteine Synthesis of NAD+	Transamination - PLP aldehyde carbon links amine group to lysine (external aldimine)
Other Functions	Serotonin synthesis - PLP decarboxylates trptophan into 5-HTP GABA synthesis from glutamate - glutamate is decarboxylated into GABA by GAD with B6 as a coenzyme Dopamine synthesis - PLP decarboxylates L-DOPA for AADC which makes dopamine Heme synthesis - PLP is a coenzyme for glycine decarboxylation of amino leulinic acid synthase Reduce Emetic responses - pridoxine and doxylamine 5-HTP blocks high levels of serotonin receptors
Related Pathways	Transsulfuration Pathway - PLP creates schiff bases for homocysteine and serine to covert to cysteine Kynurenine Pathway - helps convert tryptophan into niacin
Assessment & Status	Plasma PLP concentrations - functional assay Urine excretion of 4-pyridoxic acid Methioine load test - urine cystathionine	Treatment - pyridoxine HCL
Deficiencies	Microcytic anemia Seborrheic rash (face, neck, shoulders, butt) Cheilosis, glossitis, angular stomatitis Peripheral neuropathy	Riboflavin (FMN) helps PNPO convert PNP & PMP to PLP
Risk Factors for Deficiencies	Alcoholics Elderly are more susceptible
Mutations

Vitamin B7 - Biotin	Information	Additional Information
Functional Group	Carboxylic acid, a ureido group, and a thiophene ring	Ureido ring, thiohene ring, valeric acid side chain
Active Form(s)	Biocytin Biotinidase - free biotin	Biocytin - Biotin & lysine (via proteases)
Dietary Food	Egg yolks, organ meats, nuts, seeds, mushrooms, avocados, sweet potatoes, salmon, legumes, and spinach	Majority biocytin form
Absorption	Jejunum	Avidin (in raw egg whites) prevents biotin absorption
Transporters & Receptors	Active Transport Sodium-dependent multivitamin transporter (SMVT) at physiological concentrations Passive Diffusion A pharmacological levels	High biotin, PA, lipoic acid levels can inhibit mRNA of SMVT, inhibiting each others absorption
Reabsorption	Biotin Recycling - proteolytic is released from biotin to make biocytin which is further broken down by biotinidase for biotin recycling, holocarboxylase synthetase is needed to tether biotin to apocarboxylases
Coenzyme Functions	Biotin-Dependent Carboxylase (Biotin Bio Tether) Pyruvate carboxylase (Biotin Bio Tether) - needed for gluconeogenesis (biotin is needed for pyruvate carboxylase) Acetyl-CoA carboxylase 1 & 2 (ACC1 & ACC2) - coenzyme for carboxylation of acetyl-coA (for FA synthesis, manoyl-coA regulation with VB5) Methylcrotonyl-CoA carboxylase (of 3-methyl crotonic acid) - oxidation of produces AA leucine Propionyl-CoAcarboxylase - carboxylation PCC (bacteria fermentation, b-oxidation of odd number FA, metabolism of isoleucine & valine	Biotin Bio Tether (Site 1 & 2) - transfers Co2 (holocarboxylase synthetase tethering of biotin to apocarboxylases) Propionic acid and 3-methyl-C-CoA carboxylation is important for citric acid cycle (ATP) Needed for Branch chain AA (for ATP) & Odd chain FA ACC1 inhibition will cause excessive increase FA oxidation (overload of mitochondria, stress, decrease of ATP)
Other Functions	Biotinylation of histones - regulates histone structure and gene expression (closed chromatin & gene silencing) Biotinidase - debiotinylation of histones	Biotinylation - prevents harmful gene expression & tight DNA packing Debiotinylation - regulate accessibility of DNA for readily bind for transcription
Related Pathways	Lipogenesis Gluconeogensis
Assessment & Status
Deficiencies	Dermatitis - rash (eyes, nose, mouth, genital area) Alopecia - hair loss Lethargy Organic acidemia Neurological abnormality, depression, hallucination Propionic acidemia - ketoacidosis, accumulation of propionic acid	Ketogenic diet (low-carb) can worsen biotin deficiency
Risk Factors for Deficiencies	Rare, found in most food, good recycling ability	No toxicity reported, high intake
Mutations	Biotinidase Mutation (BTD) - inability to liberate biotin from protein (causing urine excretion of biotin and biocytin) Holocarboxylase synthetase mutation (HLCS) - cannot tether biotin to apocarboxylases

Vitamin B9 - Folate	Information	Additional Information
Functional Group	Carboxylic acids, amides, amines, alcohols, and aromatic rings	Pteridine ring (pteron), PABA, glutamic acid
Active Form(s)	5-MTHF (from 5,10-MTHF) 10-formyl-THF (from 5,10-MTHF)	Folic acid - synthetic form (fully oxidized) Folic - found in food
Dietary Food	High in leafy plants and animal foods Human & cow milk - 5-THF Bioavailability: 10-100%	Major forms in food: 5-MTHF & 10-formyl-THF
Absorption	Duodenum and jejunum	Degraded with light, heat, oxygen and acidic pH Antifolates - inhibit binding to GCG (y glutamate carboxy-peptidase) Phyate inhibits folate absorption
Transporters & Receptors	Folylpoly-y glutamate carboxypeptidase (FGCP) - catalyzes the cleaving of monoglutamate for absorption Proton-Coupled Folate Transporter (PCFT) - duodenum and jejunum Reduced Folate Carrier Protein (RCF) - transports TMP, binds anti-folate compounds (reduces folate absorption) Passive Diffusion - high concentrations of folate Folate receptors (FOLR1) - binds folate to folate binding proteins (FBP) FOLR3 - folate receptors for delivery via placenta, brain, renal tubule Dihydrofolate reductase (DHFR) - converts folic acid to DHF → THF	FGCP inhibitors inhibit FGCP activity RBC contain highest pool of folate (80%) 5-MTHF is main folate that is circulating in blood
Reabsorption	Renal tubule
Coenzyme Functions	Folate-Mediated One-Carbon Metabolism Nucleotides NADPH SAM	Folic acid → DHF (via DHFR) → THF + serine (glycine byproduct) → SHMT → 5,10-MTHF → pyrimidine synthesis → 10-formyl THR → 5-MTHF
Other Functions	Pyrimidine synthesis - 5,10-MTHF is needed for these reactions Purine synthesis - 10,formyl-THF needed Thymidylate synthesis - transfers methyl group of 5,10-MTHF to make dUMP (deoxyuridine monophosphate) → converts to dTMP (deoxythymmidline monophosphate)
Related Pathways	Folate-Methionine (Homocysteine) Cycle CNS development of neural tube
Assessment & Status	Serum concentrations Red blood cel folate concentrations Plasma homocysteine	1 DFE = 1mg folate food, 0.6mg FA fortified food, 0.5mg FA supplement
Deficiencies	Anencephaly - neural tube defect, no compatible with life Spina Bifida - spinal neural tube (may be fixed with surgery) Megaloblastic Macrocytic Anemia	Methotrexate (treatment drug) can lead to secondary folate deficiency (methotrexate binds to DHFR more than folic acid) MMA accumulation (only in b12)
Risk Factors for Deficiencies
Mutations

Vitamin B12 - Cobalamin	Information	Additional Information
Functional Group	Cyanocobalamin, 5-deoxyadenosylcobalamin, methylcobalamin	Corrin ring with cobalt, 5,6-dimethylbenzimidazole
Active Form(s)
Dietary Food	Animal products, human gut microbiota synthesis
Absorption	Ileum	Protease liberates cobalamin from TC-I
Transporters & Receptors	Transcobalamin I (TC-I) - binds to B12, protects from hydrolysis Intrinsic Factor - absorption of B12 Transcobalamin II (TC-II) - taken up by cells
Reabsorption
Coenzyme Functions	Methionine Synthetase - conversion of homocysteine to methionine Methylmalonyl-CoA mutase - conversion of methylmalonyl-CoA to succinyl-CoA (for the citric acid ATP)	VB12 is the cofactor for methionine synthestase that converts homocysteine to methionine Prevents methylmalonyl-CoA convering to MMA which causes a decrease of glutamate synthesis, succinyl-CoA
Other Functions
Related Pathways	Folate-Methionine (Homocysteine) Cycle - “folate methyl trap” recycling of 5-MTHF back to THF
Assessment & Status
Deficiencies	Megaloblastic macrocytic anemia Pernicous anemia - inhibition of IF, demyelination Peripheral neuropathy	Folate can cause secondary VB12 deficiency
Risk Factors for Deficiencies	Vegans, vegetarians
Mutations