biochem of vitamins Flashcards
Water soluble vs fat soluble
Water soluble (B1 thiamin, B2, riboflavin, B3 niacin, Pantothenic acid B5, Biotin B7, B6 pyrodoxin, Folate B9, B12, Vit C)- rapidly excreded B12 liver stores
Fat soluble: Vit A (3 retinoids), Vitamin D, Vitamin E (tocos), Vitamin K (phyllo, mena quinones), need bile, lipases and dietary fat, toxicity more common (esp starge fat), Eand K, malabsorption syndromees- Cystic fibrosis, pancreatic exocrine insufficiency, celiac disease, mineral oil intake
Vitamins involved in energy metabolism
B1, B2, Pantothenic acid, Biotin, B6 (B1, 2 3 5 6 7)
Glucose–> Glycolysis–> TCA (ATP production): B1 (TPP), B2 (FADH2), B3 (NADH), B5 (coenzyme A)
Fatty acids–> Beta oxidation: B2 (FAD), B3 (NAD), B5 (coenzyme A)
Gluconeogenesis: Biotin (B7), B3 NAD
Everything with Proteins- B6
Thiamin Vitamin B1
Active coenzyme form - Thiamin pyrophosphate TPP
Needed for PDH, BRAIN needs glucose
TCA akgdh also needs b1
GLycolysis
PDH needs B1, B2, B3, B5, lipoic acid (glycolysis and TCA)
HMP Transketolase (PPP) Also needs B1– Provides NADPH, and Ribose for fatty acid and cholesterol synthesis, maintain reduced GSH for antioxidant protection, Nicleotide synthesis
RBCs, eyes oxidant stressors
Metabolism of BCAA requires TPP B1, Maple syrup Urine disease (defect in BCaKA DH),
B 1 deficiency
Classic deficiency0 Beri Beri- (B1B1), i cant i cant, neuropathy
Dry beriberi- symmetrical impairment of sensory and motor functions of extremities esp lower extremitiry, symmpetrical muscle wasting
Wet/ edamatous beri beri- cardiomyopathy, high output CF, edema
Rice bran
Wernicke-Korsakoff syndrome
B1 deficiency Wernicke Encephalopathy (Acute life threatening)- confusion, ophalmoplegia/nystagmus, ataxia
Korsakoff syndrome (chronic neurologic condition)- confabulation, personality change, memory loss, especially anterograde amnesia
Alcoholism induced- poor diet, impaired intestinal absorption, impaired cellular utilization of thiamin
Malnourished: HIV/AIDs, cancer, hyperemesis, long term dialysis, diuretics
GIve B1 and Magnesium!!!!
Assessment of Thiamin /B1 status
RBC transketolase assay: measure RBC Transketolase activity, TPPbinding should be 85%
then add TPP should not shift
Riboflavin B2
riboFlavin/b2 = Fmn/ Fad active coenzyme forms
Redox cofactors, can participate in either one or 2 electorn redox rxns,
TCA cycle, and ETC, in FA b- oxidation
GSH reductase
Deficiecny energy metabolism, aminoacid metabolism and lipid metabolism, general and specific symptoms
Corners of mouth, phototherapy for neonatal jaundice breaks down riboflavin in infants so need B 2 supplementation, will affect RBC GSHr first
Niacin- B3
sources- dietary Niacin ( nicotinic acid in plants or nicotinomide in animal tissues)
Synthesized from tryptophan!
NAD, NADH - niacin NAD and NADPH
Glycolysis, TCA, FA b-oxidation, need NAD
ETC provides NAD
FAsynthesis and cholesterol synthesis need NADPH
HMP path gives NADPH
Niacin B3 deficiency
Pellagra- 4 Ds
Dermatitis, diarrhea, dementia, death
US
in dev countries- alcoholism
Hartnup disease- decreased Tryptophan for B3 synthesis
Pantothenic acid B5
PAN-availability, Widely distributed in nature and foods, deficiency is rare,
active forms- CoEnzyme A (CoASH, CoA), Acyl Carrier protein (ACP)
Biotin B7
food bound
Broadly distributed in many foods
Intestinal bacteria synthesize small amounts of biotin
Biotin bound to protein in foods and bound endogenously to carboxylase enzymes
Biotindidase releases biotin from dietary proteins and carboxylase enzymes for recycling of biotin
Holocarboxylase synthetase links biotin to carboxylase enzymes to obtain fully functional enzymes
Multiple carboxylase deficiency: autosomal recessive genetic defects in: Biotinidase gene, holocarboxylase synthetase gene
Many cases respond to high dose biotin therapy
Biotin B 7 Functions
Carboxylation reactions: Gluconeogenesis Pyruvate carboxylase
FA synthesis AcCoA carboxylase
BCAA (ile, val, leu) and odd chain fatty acid catabolism (Propionyl CoA carboxylase), (B- methylcrotonyl- CoA carboxylase (Leu)
Biotin B7 deficiency
Rare, Avidin in raw eggwhites binds dietary biotin making it unavailable
Rare autosomal recessive disorder- multiple carboxylase deficiecy, respond to biotin
Dry skin intractable seborrheic dermatitis
Pyridoxine- b6
active forms- PALP, PLP, PAMP, PMP
Proteins!
metabolic interconversions need Zinc, FMN- B2 riboflavin
transaminations- amino acid catabolism, non essential amino acid synthesis
histamine, NT synthesis
Homocysteine metabolism
homocystinuria type 1- due to genetic mutations in this enzyme, .5 of cases respond to high dose B6 (eye skeletal and CNS, vasculature, thromboembolism)- increased urine and plasma
VIT B6 deficiency
homocysteinemia, homocystinuria 1, increase in urinary homocystine, inc. plasma homocysteine, inc. plasma methionin, thromboembolism
B6 deficiency inducible by isoniazid, oral contraceptives
Nutrients that influence cell (DNA replcation, Single carbon metabolism and methylation reacitons
Folate - B9 (Plant foods) Vitamin B12 (only animal foods, neurological
Folate Vitamin B9
Functions- DNA replication and cell replication, Single carbon metabolism
Maintain adequate amounts of methionein (SAM) for numerous methylation reactions
Methylation of DNA- epigenetic regulation of gene expression during fetal development and beyond
Influences homocystein levels, embryonic neural tube formation, interacts with B 12 and B6
food folate- folate conjugase removes polyglutamate tail, inhibited by ALCOHOL
DHFreductase, two step rxn inhibited by methotrexate
Purine, thymin and methioning synthesis
folate deficiency
Nuclear hypersegmentation of PMNs, Macrocytic anemia (B12 deficiency) megaloblastic changes, DNA Strand breaks
increased risk of neural tube defects, elevated homocysteine levels, DNA instability, dysregulated gene transcription- implication for cancer risk, low folate –> increased risk of several cancers, HPV women
ALcohol abuse
Folate status- urinary FIGLU (histidine Load)
Vitamin B 12 (cobalamin)
Contains Cobalt- active forms- methylcobalamine, deoxyadenosylcobalamin
Synthesized by intestinal bacteria, is enterohepatically circulated, found in animal foods
only found in animals Methionine Synthase (SAM pathway for methylation reactions, recycling folate, homocysteine --> methionen
Methyl malonyl mutase- Increased MMA is specific for B12
GRAMA - neuro stuff
Vit B 12 deficiency
Dietary Deficiency- B12 only in animal foods, vegan diets
Stomach (inadequate HCl, IF), Atrophic gastritis (affects 30% of elderly, incidence increases w/ age), pernicious anemia, longterm proton pump inhibition, gastrectomy/ gastric bypass
metformin , pacreatic insufficiency,
vitamin E- tocopherols
8 forms good antioxidant localized to membranes fat soluble- unsaturated fatty acids protection against oxidation Aging smoking, etc
Chain breaking antioxidant
Vitamin E dependence of vitamin C
Vitamin C can regenerate Vitamin E
Severe deficiency of vitamin E
Hemolytic anemia (premature infants), premies miss the fat/fat soluble vitamin transfer that occurs very late in pregnancy
Neuro symptoms- impaired balance/ coordination (ataxia), peripheral neuropathy, myopathy, pigmented retinopathy
can be caused by Fat malasorption (biliary obstruction, cystic fibrosis, cholestatic liver disease, pancreatitis)
CVD , cognitive decline, macular regen
Vitamin C (ascorbic acid)
Antioxidant, enhances iron absorption
Post translationonal modification of collagen synthesis- scurvy
bruise, gums, hair skin
Tissues concentrate vitamin C esp brain and adrenals
cigarette smoking will decrease vit C
collagen , wound healing
vitamin A Retinoids forms and functions
retinol: reproduction, major transport form (RBP), Storage form as retinyl esters, major food form, Spermatogenesis, treats measles, severe acne
Retinal-vision (rhodopsin)
Retinoic acid- normal epithelial cell differentiation/ maintenance, embryonic developent, immune function, treats acute promyelocytic leukemia
needs Zn, full form from animals
Vitamin A deficiency
Decreased resistance to infection, impaired immunity
Increased morbidity and mortality, impaired immunity occurs before eye symtomps
Stunted growth, rough skin, thick dry scaly skin, follicular hyperkeratosis, Night blindness (nyctalopia), Bitots spots, xeropthalmia, Blindness, worldwide leading cause of irreversible blindness
Vitamin A toxicity
Nausea, vomiting, headache, irritability, myalgia, arthralgia
Dry lips, dry skin, mucous membranes, alopecia
Teratogenic effects (craniofacial, CNS, Cardio-vascular, thymus malformation- isotretinoin can mess with kids
Toxicity with active fully formed vit A (animal products), B- carotene is not associated with vitamin A toxicity
vitamin D
cholesterol, its a hormone, in skin, light partially activates it
D3 better- liver partially activates it
Calcitriol 1, 25 (1 alpha hydroxylase)
Rickets ets
Function- sunlight and food, gene expressor, RXR (vitamin A)
Intestine increases absorption of Ca, P, bone mineralization, immune cells, induces differentiation, tumor mucroenvironment- tumor necrosis
Muscle maintanence, cell differentiation, immune modulation
Vitamin D deficiency
Rickets, osteomalacia, msk pain, muscle weakness, hypocalcemic tetany, long term: osteoporosis
cod liver oil
Toxicity- hyper calcemia, calciuria
Vitamin K
Diet- phylo quinones- green leafy plant foods, menaquinones animal foods
Intestinal bacteria synthesize vit K
Liver storage and site of vit K dependent coagulation protein synthesis
Koragulation
Calcium and vitamiin K in bone osteocalcin post translational y carboxylation of glutamte GLU residues in proteins
Deficeicny- bleeding issues, Antibiotics, neonatal hemorrhage
