Week 6 Flashcards
What are vitamins?
Essential micronutrients
• must be provided by dietary source
• compounds not synthesized by the host in amounts adequate to meet normal physiological needs
Organic compounds
• Distinct from other essential micronutrient minerals
• Distinct from other organic compounds in the diet, i.e. macronutrients (fats, carbohydrates, and proteins)
Natural components of foods, present in minute amounts
• Low intakes can cause deficiency diseases
Water-soluble vitamins
- not readily stored - easily excreted
- consistent daily intake is important
- many synthesised by bacteria
Lipid-soluble vitamins
- can accumulate in body
- more likely to lead to hyperviterminosis
Functions of vitamin A
- vision
† Retinal binds to opsin to form rhodopsin in rods, iodopsin in cones
† Essential for signalling - control of gene expression via transcription factors
† Binding of retinoic acid activates receptors (RAR/RXR)
† RAR/RXR bind DNA
† Activate/repress gene expression
Vitamin A deficiencies
• Vision
† Nightblindness,
† Xerophthalmia (conjunctival ulcers)
• Teratogenic
† Excess is also teratogenic
† Crucial role of the Hox genes in embryogenesis
• Impaired immunity
• Anaemia
• Ostopenia
• Inappropriate bone depositio
Vitamin A toxicity
Causes
• Rarely from diet – sometimes consumption of animal livers
• Medication - 13-cis-Retinoic Acid (brand name ”Accutane”) can be used therapeutically to treat acne
Teratogenic
• Vitamin A effects expression of genes involved in embryogenesis
Idiopathic increased intracranial pressure
• Headache
• Vomiting
• Impairedconsciousness
Role of Vitamin D in Ca2+ homeostasis
• Vitamin D is involved in Ca2+ homeostasis
† Mediated by parathyroid hormone (PTH) – senses low Ca2+
• PTH promotes formation of active Vitamin D
† Negative feedback loop – High calcitriolàinactive PTH
† Homeostatic regulation
• Mechanisms:
†Renal reabsorption
† Intestinal absorption
† Mobilisation from bone (osteoclasts)
Vitamin D deficiency
Causes
• Provitamin D malabsorption
• Lack of UV
Osteomalacia (rickets)
• Low Ca2+
• Soft, pliable bones
• Impaired ossification
Vitamins K
K1 (phylloquinones)
K2 (menaquinones)
Found in plants
• e- acceptor in photosynthesis Converted from K1 by bacteria
• Found in fermented foods
Breaks naming convention
• named for German term meaning “coagulation vitamin”
(Koagulationsvitamin)
Function of Vitamin K: Gla proteins
Needed to activate Gla proteins
• Vit K is oxidised to quinone form
• Provides reducing power – acts as a cofactor for a carboxylase enzyme
• Adds a second carboxyl group to glutamic acid of certain proteins
• Glu residues → Gla residues
Effect
• Gla proteins can bind Ca2+
• Many proteins need to be carboxylated on glutamic acid residues to be active
To recycle oxidized Vitamin K it is reduced by 2 additional enzymes
Examples of Gla proteins
Blood coagulation
• Procoagulant: prothrombin (factor II), factors VII, IX, X
• Anticoagulant: proteins C, S, Z
Bone metabolism
• Osteoblast activity: Osteocalcin (Bone Gla Protein)
• Bone mineralisation: Matrix Gla protein (MGP)
Metabolism of blood vessels
• Arterial calcification: MGP
Tissue remodeling, cell fate changes
• Wound healing: Periostin
Vitamin K deficiency
Causes
• Abundant in diet, rare
• Lipid malabsorption
• Anticoagulant therapy
• Antibiotic therapy
Blood clotting disorders
• Important role of Gla proteins in coagulation factors and anticoagulant proteins
• Dangerous in newborns – injection given after birth
Osteoporosis
• Decreased activity of osteoblasts
Warfarin is a Vitamin K antagonist
• Over dose can be treated with Vit K
Vitamin E (tocopherol)
A family of tocopherols
(α-, β-, Ɣ-, δ-)
α-tocopherol
• highest biological activity
• most common
Dietary source
• Vegetable oils
Lipid Peroxidation
Caused by free radicals
• Fenton reaction (Fe2+) produces hydroxyl radical (OH-)
• Byproduct of metabolism
• Oxidative burst of immune cells
Lipid peroxidation is a chain reaction
• Oxidation of one lipid forms a free radical, oxidises further lipids
Targets
• PUFAs in biological membranes are susceptible
Vitamin E function
Enzyme cofactor
• α-tocopherol quinone acts as a cofactor of mitochondrial unsaturated FA synthesis
Antioxidant
• Stops free radical chain reactions
• Sacrificially oxidised to tocopheroxyl
• Can be recycled (reduced) back to tocopherol
Vitamin E deficiency and toxicity
Causes of deficiency
• Rarely from diet
• α-TTP mutations
• Fat malabsorption
• Peripheral neuropathy (Neurons: High levels of PUFA, Iron)
• Anemia, RBClifespan (RBC: High levels of PUFA)
Supra-physiological doses
• Stimulate immune system (e.g. Antibody production, mechanism is unclear)
• Cardiovascular health (Prevents oxidation of LDLs → involved in atherosclerosis)
Toxicity
• Rare, can tolerate large doses
• Antagonise functions of other fat - soluble vitamins (e.g. bleeding (VitK)
Vitamin C (Ascorbic acid)
• Synthesized by plants and other animals, but not humans
• Easily oxidized - not stable in stored or cooked foods
• Name comes from its “anti- scurvy” properties: “a-scorbic” vitamin
Vitamin C functions
Cellular respiration
• Electron transport reactions
Antioxidant
• Redox recycling of ɑ-tocopherol, glutathione
Bioavailability of iron
• Ferrous form is more easily absorbed
• Ascorbate can reduce Fe3+ (ferric) → Fe2+ (ferrous)
• Increases transferrin - mediated iron uptake
• Increases ferritin translation, decreases ferritin degradation
• Increased storage of iron
Collagen synthesis
• Involved in hydroxylation of procollagen → stability of the protein
Immune system
• B and T-lymphocyte differentiation
• Phagocyte & leukocyte activity
Vitamin C deficiency
Subclinical
• e.g.accumulation of lipid peroxidation products in retinal tissues
Scurvy
• Effect on collagen formation
† Mesenchymal tissues display signs
• Liver spots
• Spongy gums
• Bleeding from mucous membranes
• Lethargy
• Rheumatic pains
• Edema (swelling)
• Hemorrhage
Advanced Scurvy
• Open wounds
• Loss of teeth
Vitamin B deficiencies
Causes relating to low intake
• Processed foods (white rice, white flour…)
† Mandatory fortification of grains with thiamin (B1) and folic acid
• Severe malnutrition
Causes relating to malabsorption
• Heavy alcohol use
† (especially thiamine B1, B3, folic acid B9, B6)
• Diseases which damage the intestines
† Inflammatory Bowel Disease (Crohn’s disease), Celiac Disease
Some genetic disorders affecting enzymes which have vitamins as a cofactor can mimic deficiency
Vitamin B1 (thiamine or thiamin)
† Active coenzyme is thymine pyrophosphate (TPP)
† TPP is a cofactor for decarboxylation reactions in the action of many enzymes, including:
• pyruvate dehydrogenase
• α-ketoglutarate dehydrogenase
• transketolase (pentose phosphate pathway)
Vitamin B1 deficiency
Mild
•GI complaints
• weakness
Moderate
• peripheral neuropathy
• mental abnormalities
• ataxia
Full-blown deficiency: “Beriberi”
• muscle wasting
• congestive heart failure
• delirium
• memory loss
• Now uncommon except in displaced (refugee) populations.
• Diet of polished (white) rice is a cause. Supplementing or rice bran ensures adequate intake.
† In Australia, bread must be fortified.
• Alcoholism can impair uptake and utilisation of B1 (Wernicke-Korsakoff syndrome)
• Acute complication of bariatric surgery (reduction of stomach size)
Vitamin B2 (riboflavin)
Active coenzymes are
• flavin mononucleotide (FMN)
• flavin adenine dinucleotide (FAD)
FMN and FAD act as prosthetic groups in many redox enzymes in
• Carbohydrate metabolism (TCA cycle)
• b-oxidation of fatty acids
• The electron transport chain
Vitamin B2 deficiency
• More common in displaced populations, poverty
• Can occur with malabsorptive syndromes (e.g. Celiac disease); anorexia nervosa
• Rare: inborn error of metabolism e.g. non-functional riboflavin transporter; riboflavin-dependent enzymes Vitamins are lost in processing many grains.
• Grain fortification: restores these nutrients.
• Mild, nonspecific symptoms
• Rarely occurs without other deficiency
• Inflammation of the lining of mouth and tongue
• Dry and scaling skin, keratitis, dermatitis
• Iron-deficiency anaemia
• Mental depression, forgetfulness
Vitamin B3 (niacin)
2 forms (vitamers):
• nicotinic acid
• nicotinamide
Active coenzymes are :
• NAD+ (nicotinamide adenine dinucleotide)
• NADP+ (nicotinamide adenine dinucleotide phosphate)
Biosynthesis of vitamin B3
† Liver can synthesise niacin from tryptophan
• Tryptophan is an essential AA
• 60 mg of tryptophanà1 mg of niacin
• Requires vitamin B6
† Gut bacteria may also convert TrpàNiacin
† Both processes are inefficient and very slow
† Effectively, Vitamin B3 (niacin) must be supplied in diet
Vitamin B3 functions
NAD+ and NADP+ are cofactors in:
• Carbohydrate metabolism (glycolysis, TCAcycle)
• Pentose phosphate pathway
• β-oxidation of fatty acids
• Amino acid synthesis
• Nucleotide synthesis
Vitamin B3 deficiency Pellagra (raw skin)
“the four D’s”:
• diarrhoea
• dermatitis
• dementia
• death
Milder deficiency
• Fatigue
• Irritability
• Poorappetite
• Headache
• Very rare. Maybe present in alcoholics, strict vegetarians, and populations with poor nutrition
• Some drugs inhibit conversion of tryptophan into niacin –including azathioprine (immunosuppressant), chloramphenicol (antibiotic), phenobarbital (anti-seizure medication)
Vitamin B5 (Pantothenic Acid)
• Active coenzyme is acetyl CoA
CoA is a cofactor for
• TCA cycle
• Metabolism of fatty acids
• Formation of sterols (cholesterol and 7-dehydrocholesterol)
Vitamin B5 deficiency
• “Burning feet” - distal paresthesias
• Gastrointestinal distress
Extremely rare
• Present in almost all foods
• Severe malnutrition
• Symptoms are somewhat non-specific
• Defects in pathway for CoA synthesis can occur
• Processing can cause losses (20-80%)
• Many processed foods are fortified (not mandatory in Australia for B5)
Vitamin B6 (pyridoxine)
3 vitamers
• Pyridoxine, pyridoxal, pyridoxamine
• Active coenzyme is pyridoxalphosphate (PLP)
Vitamin B6 functions
• Amino acid synthesis, glycogenolysis
• Cofactor for glycogen phosphorylase
• >100 enzymes for protein metabolism
Essential for :
• RBC metabolism, haemoglobin formation
• Nervous and immune system function
Vitamin B6 deficiency
Neurological
• Depression
• Confusion
• Seizures
Skin
• Dermatitis
• Stomatitis
• Glossitis
Present in most foods, so it is rare
Occurs due to:
• Malabsorption
• Highlevelsofalcoholuse
• Pyridoxine–inactivatingdrugs
(eg. corticosteroids)
• Haemodialysis
Vitamin B7 (biotin)
Coenzyme for several metabolic pathways
• Carbohydrates
• Fats
• Proteins
• Prosthetic group of several carboxylase enzymes
† Pyruvate carboxylase (gluconeogenesis)
† Acetyl CoA carboxylase (FAsynthesis)
• Is made by gut bacteria – unclear how much more is needed from diet
Vitamin B7 deficiency
• Deficiency rarely caused by lack of intake
• Additionally, some synthesized by intestinal bacteria
• Symptoms are somewhat non- specific:
† Dermatitis around eyes, nose and mouth; alopecia
† Neurologic symptoms
Deficiency can be caused by other factors, including:
• Consumption of egg whites
† Protein (avidin) binds biotin very strongly
• Deficit in biotinidase enzyme – required to release protein- bound biotin, make biologically available
Vitamin B9 (folate)
Active coenzyme is tetrahydrofolate (THF)
Vitamin B9 functions
• THF is coenzyme of many transferases
• Role in nucleotide and nucleic acid synthesis
Vitamin B9 deficiency
• Rare
• Is absorbed passively, and mediated by carrier
Symptoms:
• Anaemia (macrocytic)
• Peripheral neuropathy
• Increased circulating homocysteine (CVD risk)
Special case: pregnant people
• Deficiency: neural tube defects (Spina bifida) • Grains now supplemented
• Public health success story
Vitamin B12 (cobalamin)
Metabolically active cofactors:
• Methylcobalamin (R: -CH3)
• Adenosylcobalamin (R: -Ado)
Cofactor for
• Energy synthesis
† FA oxidation
• DNA synthesis
• Methionine synthase
Essential for:
• RBC maturation
• Cell growth
• Formation of myelin
• DNA synthesis
Vitamin B12 deficiency
30-40% of adults are deficient – develops slowly as body stores some B12
• Anaemia (reduced number RBC)
• Fatigue
• Decreased taste (loss of papillae / hyperpigmentation of the tongue)
• Reflex changes (reduced myelin synthesis, due to reduced methionine synthesis)
• Slowed mentation
• Can result in permanent nerve damage
Poor absorption
• Intestinal parasites, pernicious anemia, removal of stomach, genetic disorders
Improper management of vegetarian diet
• Not present in plant foods
• Present in yeast
Genetic disorders
• Receptor-mediated uptake – requires intrinsic factor
