Vitamins Flashcards
What are vitamins?
organic compounds required in small amounts for normal functioning of the body
- cannot be synthesised in the body
- must be provided by diet
What are the general outcomes of vitamin toxicity?
- abnormal accumulation in tissues
- overloading of normal metabolic pathways
- possibly irreversible lesions
What are some vitamins that are toxic in access?
- vitamin A, D, B6
- niacin
(possibly Vitamin C, beta-carotene, vitamin E)
What is produced from the reduction of oxygen to water in mitochondria?
- produces ATP
- produces free radicals
What happens to 1-2% of the O2 used by respiratory chain?
ends up as superoxide
What are free radicals?
- unstable oxygen species
- capable of oxidising PUFA/damaging organs/tissues and DNA (@ cell mem = lipid peroxidation)
- contains one or more unpaired electrons
- capable of independent existence
What damage do free radicals do?
- nucleic acids
- nucleotides
- thiols
- covalent bonding
- lipids
- membrane structure
What diseases can develop from free radicals?
- heart disease
- cancers
- parkinsons
- arthritis
- cataracts
- muscular dystrophy
Where can we get some nutrients that act as protective antioxidants in conjunction with body enzymes?
- fruits, nuts
- leafy greens
- juices
What are some metal cofactors that contribute to the integrated antioxidant defence system?
- Selenium (GSHPx, X 4)
- Iron (catalase)
- Copper (SOD, ceruloplasmin)
- Zinc (SOD)
- Manganese (SOD)
What are some antioxidant compounds integrated into antioxidant defence system?
- vitamin E (carotenoids)
- vitamin C (polyphenols)
What are fat soluble vitamins?
- found in fats and oils of food
- absorbed into lymph and carried in blood with protein transporters (chylomicrons)
- require bile and fats for absorption
- stored in liver/body fat
- can be toxic if large amounts consumed
- normally not excreted in urine
- don’t act as coenzymes
What are soluble vitamins?
- found in vegetables, fruits, grains, meat
- absorbed into bloodstream
- not stored in body (except B12)
- toxicity is rare, when large amounts consumed
- have threshold for urinary excretion
- act as co-enzymes
Name 4 lipid (fat) soluble vitamins:
- vitamin A
- vitamin D2
- vitamin E
- vitamin K1
What is vitamin A also known as?
retinol
What are the requirements, biological activity, and sources of vitamin A?
- 0.8mg
- eyesight, immune system
- liver, cheese, eggs and oily fish
What are the requirements, biological activity, and sources of vitamin D?
- 0.01mg
- bones and teeth
- oily fish and eggs
What are the requirements, biological activity, and sources of vitamin E?
- 10mg
- antioxidant activity
- cereals, vegetable oils, leafy vegetables
What are the requirements, biological activity, and sources of vitamin K?
- (not stated requirement)
- blood clotting
- leafy vegetables, dairy products, grains
what is ß-carotene?
- human body converts beta carotene into vitamin A (retinol)
- beta carotene is a precursor of vitamin A.
How much retinol is absorbed by the body (%)?
70-90%
How much ß-carotene is absorbed by the body (%)?
20-50%
How much ß-carotene is needed for the formation of 1 µg of retinol?
6µg
Where is ß-carotene stored?
liver
What can retinyl esters form and what is the use of its product?
- 11-cis-retinal
- chromophore for rhodopsin
What can retinoic acid form and what is the use of its product?
- all-trans and 9-cis-retinoic acid
- transcriptionally active vit. A species
How is free retinol esterified to form retinyl esters?
- via ARAT
or - bind to CRBP and esterified by LRAT
Where are retinyl esters stored until needed?
in liver stellate cells
Roughly explain the Hepatic vitamin A metabolism:
- Retinyl esters taken up into liver cells
- Free retinol is esterified to retinyl esters
- CRBP-retinol has a few pathways
- converted to retinoic acid
- released into blood
- form retinyl ß-glucoronide for excretion in bile - Retinoic acid has few pathways
- gene expression
- conjugated to glucaronic acid and excreted in bile
- 4-oxoretinoic acid - 4-oxoretinoic acid either function like retinoic acid or excretion in bile as glucaronic acid
- holo-RBP from retinol, released to blood to form trimolecular complex
Main functions of vitamin A:
- Vision
- night vision
- forms visual molecule rhodopsin - Antioxidant
- ß-carotene/other carotenoids, reacting with singlet oxygen species - Gene expression (differentiation + growth)
- Immune system function
- Reproductive process
- Bone metabolism
What are two specific vitamin roles in the eye?
- Process of light perception at retina
2. Maintenance of healthy cornea
What enables the signal that light hits the eyes, to be received by the brain?
rhodopsin in rod cells that are transformed and sends signals
How does vitamin A help the immune systems’ function?
- synthesis of glycoproteins
- promotes development of immune cells (NK cells)
How does vitamin A help the reproductive process?
- gene transcription in testis
- placental development
- testosterone/oestrogen production
What % of vit. A is egested in faeces?
70%
What % of vit. A is excreted in urine?
30%
Where else apart from faeces and urine, is vit. A excreted?
- CO2 from lungs and - caretenoid metabolites in bile
What is the require amounts of vitamin A for men and women?
men = 1000 µg/day women = 800 µg/day
What is the minimum vitamin A intake per day?
600µg
What are the results of high intake/chronic intake of vitamin A?
- in early pregnancy = birth defects
- anorexia, skin/hair abnormalities, bone/muscle pain
- ß-carotene cause yellow discolouration of skin (fat pads)
What are the results of vitamin deficiency?
- skin/mucous membrane dryness + infection + keratin deposits
- anaemia
- impaired immune response
- developmental defects (bones, teeth, immune system, vision)
- eye problems
Name 4 specific ways vitamin A deficiency causes eye problems:
- Squamous metaplasia + keratinisation of conjunctiva
- Dryness wrinkling + thickening of cornea (xerophthalmia)
- Ulceration of cornea (blindness)
- Impaired colour vision
What are the toxic effects of vit. C?
- fragile RBC, haemmorage
- bone pain, fractures
- abdominal pain, diarrhea
- blurred vision
- dry skin, hair loss
- liver englargement
- death
What are the (animal) sources of retinol?
- egg yolk
- butter
- whole milk
- liver/fish liver oils
What are the (plant) sources of ß-carotene?
- dark green leafy vegetables
- yellow/orange vegetables = carrots
What is vitamin D?
- steroid pro hormone
- made under the skin in UV light presence
What is the mean vitamin D intake required?
serum 25(OH)D concentration ≥ 25 nmol/L
General outcome of vit. D deficiency?
- rickets (children)
- osteomalacia (adults)
Which vitamin is the most potentially toxic?
vitamin D
Explain how we synthesise vitamin D:
- UV light shines on cholesterol compound in human skin
- Transformed into vit. D precursor + absorbed to blood
- Next day, liver and kidneys finish converting precursor to vit. D
25(OH)D (vitamin D) compound is needed in 4 areas, what are they?
- Intestine - increase absorption of Ca2+ and P
- Bone - increase boe mineralisation
- Immune cells - induces differentiation
- Tumour microenvironment
- inhibits proliferation
- induces differentiation
- inhibits angiogenesis
What is the final form of vitamin D when synthesised?
calcitroic acid
Which form of vit. D doesn’t require digestion?
D2 and D3
Vit. D is absorbed via a _____ with the aid of ____ by _____ into the intestinal cell.
- micelle
- bile salts
- passive diffusion
What is vit. D incorporated into for transport into lymphatic system and blood?
chylomicrons
What is the % of dietary vit. D absorbed?
50%
How is excessive production of vit. D in skin prevented?
through inactive metabolite generation (lumisterol)
In liver, what hydroxylates vitamin D to active form?
cytochrome p450 hydroxylases
What is the half life of active vitamin D?
15 days to 3 weeks
What are the genomic and non-genomic functions of vitamin D?
- Serum calcium homeostasis (kidney, bone)
- Phosphorus homeostasis
- Cell differentiation, proliferation, growth
- Calcitriol and muscle
- Blood pressure regulation
- Immune function
- Pancreatic beta-cell production, insulin secretion
What does vitamin E refer to?
group of 8 tocopherols
Which tocopherol is the biologically active form?
A-tocopherol
What are the functions of Vit. E?
- Antioxidant
- Prevent damage to lungs, RBCs, WBCs (immunity), heart
- Necessary for normal nerve development
What is the result of vitamin E deficiency?
- Decreased absorption of fats
- liver disease
- low fat diets
- premature babies - fragile RBCs (haemolysis)
- Loss muscle coordination, vision, immune function
What is the exceeding upper intake of vit. E?
1000 mg/day
Which vitamin is the least toxic from the fat-soluble vitamin list?
Vitamin E
What might extreme doses of vitamin E cause?
- affect blood clotting effects of vit K
- increased haemmorage
- increase effects of anticoagulants (coumadin, warfarin)
What can destroy vit. E?
high temperatures
What is the daily recommended intake for Vit. E?
15mg
What are some sources of vit. E?
- safflower oil
- mayonnaise
- canola oil
- wheat germ
- sunflower seeds
What and which part produces vitamin K?
produced by bacteria, in the large intestines
What are the functions of vitamin K?
- Coagulation
- Promotes synthesis of blood clotting proteins (interfere with anti-coagulants
- Bone formation
What was vitamin K named after?
Danish word, “koagulation”
What are the recommended daily intakes of vit. K for men and women?
men = 120µg women = 90µg
What are good sources of vit. K?
- cauliflower
- cabbage
- canola oil
- spinach (steamed)
- salad greens
- soybeans (dry roasted)
Are there any vitamin K deficiencies?
rare, unlikely in healthy adult
Which populations are at risk of vitamin K deficiency?
- infants (after prolonged antibiotic therapy)
- patients with decreased bile production
- patients with chronic malabsorptive disorders
Why are infants given vit. K injection?
- milk is low in vit K
- low vit K stores at blood
- GI not populated with vit K producing bacteria
What is the result of vit. K toxicity?
- ingestion of large amounts doesn’t cause toxicity but maybe above >1000mg/d
- haemolytic anaemia (rupture of RBCs)
- liver damage (jaundice)
What are the water-soluble vitamins?
non-B complex (vit. C) and B-complex
Who cannot synthesise vit. C?
- humans
- guinea pigs, primates, birds
Why can’t humans synthesise vit. C?
have congenital absense of gulonolactone oxidase
What was used in the experiment to cure scurvy, 250 years ago?
lemons
Vitamin C is also known as?
ascorbic acid
What are the main food sources of vitamin C?
fruits and vegetables
What are the main deficiency symptoms of vit. C?
- scurvy
- capillary fragility
Does vitamin require digestion prior to absorption?
No
What assists absorption of ascorbic acid?
- sodium dependent vit. C transporters (SVCT 1 and 2)
What is SVCT1?
- main carrier responsible for vit C absorption
- enables intestinal absorption of vitamin in excess of cell needs
- downregulated by ascorbic acid
What is SVCT2?
present in most metabolically active tissues except muscle/lungs
What is involved in transport of dehydroascorbic uptake into cells?
GLUT transporters
What generally happens in interconversion of ascorbic acid and dehydroascorbic acid?
- Ascorbyl radical formed but has short half-life - doesn’t form ROS
- Oxidation of this radical forms vit. C
- Dehydroascorbic acid reduced to ascorbin acid with H provided from reduced glutathione (GSH)
What is the range of recommended vit. C intake per day?
30-180mg
What is the % of absorption?
70-90%
What is the relationship of absorption and intake?
Absorption decreases with increased intake
At what levels of vit. C is is there 98% absorption?
> 20mg
What is the normal plasma ascorbic acid concentration range?
0.4-1.7mg/dL
Where in the body are is the highest level of vit C plasma concentration and how much?
adrenal and pituitary glands
30-50mg/100g
But where in the body contains the most vitamin C?
liver
What is the maximum vitamin C pool taken per day?
2g
What can result from taking more than 2g vit. C a day?
- alteration of insulin response to carbohydrate
- interference with blood clotting medications
- kidney stones
- gout
- digestive upsets
How is vit C excreted?
in urine after chemical reactions as various metabolites, 25% in form of oxalic acid
What can high doses of vit. C result in?
- formation of kidney stones, from overproduction of oxalate
- DNA damage (500mg/d)
In terms of its function as antioxidant, what roles do vit. C play?
- React with many reactive free radicals
- Powerful, non-specific reducing agent, H donator
- Protects water soluble compartments
- Neutralises free radicals
- Regenerates Vit. E (H donor)
How can the vit E radical be converted back to vit E?
reaction with vit C
Explain the amidation of peptides with c-terminal glycine (involves vit. C):
- Vit. C = reducing agent, converts copper to reduced form
- enzyme cleaves carboxyl-terminal residue, residue released as glyoxylate
- Amidated peptides are active hormones/hormone-releasing factors/neurotransmitters
What are other functions of vit. C?
- Collagen/carnitine synthesis
- Facilitates Fe (non haem) absorption
- Co-factor in mono-oxidase reactions - neurotransmitter synthesis
- Activation of peptide hormones
- Tyrosine synthesis (liver and kidney - from phenylalanine)
- Cholesterol catabolism
- Bile acid formation
What is the function of ascorbate?
hydroxylation of peptide-bound proline and lysine in the synthesis of collagen
What are the 3 interwoven chains of collagen?
glycine, proline and hydroxyproline
What is the use of carnitine?
transfer long chain FAs to inner mitochondria mem. for energy production
Tyrosine is synthesised from?
amino acid phenylalanine
What are the symptoms of vit. C deficiency?
- bleeding gums
- small skin discolouration (ruptured blood vessels)
- sub-lingual haemmorages
- easy bruising
- impaired wound and fracture healing
- joint pain
- loose/decaying teeth
How many b-complex vitamins do we know of?
8
What are the b-complex vitamins?
water-soluble, chemically distinct vitamins that coexist in same foods
What is the function of the b-vitamins?
- coenzymes
- important for cells to generate energy, make protein/new cells, metabolise carbs/fats/proteins
What is a coenzyme?
molecule that combines with enzyme to make it active
What is vitamin B1 known as?
Thiamine
What does the deficiency of thiamine cause?
- beri-beri
- possible edema
- muscle wasting, weakness
- pain, apathy
etc (so much)
What is beri-beri?
disease that was widespread in Asia, leg paralysis (polyneuritis)
- primary symptom = anorexia
- progresses to cardiovascular/neurological problems
What is the recommended intake for vit. B1 (thiamine)?
0.5mg/1000kcal
What is the dose at which vit. B1 is toxic?
300mg
What are the sources of vit. B1?
- meats (pork, beef)
- salmon
- legumes, grain products
- cereals, breads
- yeast, wheat germ, soy milk
What are the 3 functions of thiamine (vit. B1)?
- Energy transformation
- Synthesis of pentoses and NADPH
- Membrane/nerve conduction
How many metabolites does degradation break thiamine to?
20 or more
What does wet beri-beri cause (reversible)?
- cardiomegaly
- edema
- waxy skin
What does dry beri-beri cause (reversible)?
- peripheral neuropathy
- weakness
What is the results of irreversible beri-beri?
- cerebral beri-beri like:
- Wernicke-Kosakoff syndrome
- brain tissue damage
How does alcoholism affect thiamine?
- thiamine deficiency related to alcohol consumption
- alcohol inhibits absorption of thiamine in mucosal cells + conversion to TPP
- symptoms: mental confusion, loss recent memory, ataxia
What is vitamin B2 known as?
Riboflavin
Explain vit. B2 absorption:
- digested from protein prior to absorp.
- via saturable, energy-dependent Na+-independent carrier (9RTF2)
- in large amounts, absorbed via diffusion
- bile facilitates absorp.
- alcohol impairs digestion + absorp.
- 95% absorp.
What is the maximum in g of vit. B2 absorbed per day?
25g
What are the functions of vit. B2?
- energy metabolism
- flavoproteins (fatty acid beta-oxidation)
Is B2 affected by B1?
Yes, it is low when B1 is low.
What are the daily recommendations of vit. B2 for men and women?
men = 1.2mg/d women = 1.1mg.d
What are the results of vit. B2 deficiency?
- cracks/redness at mouth corners
- sore throat
- inflamed eyes/eyelids
- sensitivity to light/skin rashes
What is Vitamin B3 known as?
Niacin
How was niacin discovered?
through its deficiency - pellagra
Niacin is a generic term for?
nicotinin acid and nicotinamide
Niacin absorption is dependent on…?
Na+-dependent, carrier mediated diffusion
At what g is there complete absorption of B3 (niacin)?
3-4g
What are the functions of niacin?
- Coenzyme
- b-oxidation of fatty acids
- fatty acid/cholesterol/hormone synthesis - Non-redox roles (donor of ADP)
- Energy metabolism
- Cell respiration
- DNA repair/synthesis
- Act as secondary messenger
- Stimulate increased Ca2+
What are the symptoms of pellagra (hint: 4Ds)?
- Dermatitis (sunburn-like skin)
- Dementia (neurological, headache, memory loss)
- Diarrhoea (+ vomiting)
- Death
What re the recommended daily intakes of vit. B3 (niacin) for men and women?
men = 16mg women = 14mg
What is the tolerable upper intake level of B3?
35mg/day
What is pantothenic acid bound as?
coenzyme A (CoA)
What reactions do CoA participate in?
- nutrient metabolism
- energy production (TCA cycle)
- Acyl-carrier protein (ACP)
What results from pantothenic acid deficiency?
Burning feet syndrome
What was biotin usually called?
Vitamin H or B7
Although rare, when the biotin deficiency occur?
in patients treated with anticonvulsnts/antibiotics
What synthesises significant quantities of biotin?
- intestinal flora
What does avidin do?
- irreversibly binds to biotin
- prevents biotin absorption (not heat resistant)
What is the tightest non-covalent bond found in nature?
avidin binding with biotin
What are the coenzyme forms of folate?
DHF and THF
What is folate known as?
Vitamin B9
What are the functions of folate?
- Amino acid metabolism
2. Purine and pyrimidine synthesis/nucleotide metabolism
What is the recommended daily intake of folate (vit. B9) for adults?
400μg/d
When would there be requirement of additional dietary intakes of folate?
during pregnancy and lactation
What are the sources of folate?
- leafy green vegetables
- liver, kidney beans, lima beans
- leaf beef, potatoes, whole grain bread
- excludes oranges and root vegetables
What destroys half of folate in foods?
heat and oxidation during cooking/storage
What is the % of dietary folate that is nutritionally available?
25-50%
What are the results of folate (B9) deficiency?
- anaemia, mental confusion
- increase of neural tube defects, anencephaly, absence of cerebral hemisphere
- alterations in DNA metabolism
- changes in cellular nuclear morphology
- poor growth, GI tract disturbances
How does a women achieve maximum benefit from folate supplementation?
enhance her folic acid intake before she becomes pregnant
Why is vitamin B12 unique?
contains metal ion, cobalt
What is required for B12 absorption?
intrinsic factor
What are the functions of B12?
- Methyl transfer reactions (with folate)
- Homocysteine to methionine
- DNA/RNA
- L-methylmalonyl-coA to succinyl-coA
- Fat and protein metabolism
- Haemoglobin metabolism
What are sources of B12?
- food from animals
- liver and kidney
- milk, egg, fish, cheese, meat
When how much B12 is lost % when milk is pasteurised or evaporated?
40-90%
What is the recommended intake of B12 in adults?
2.4μg/d
What are the results of vitamin B12 deficiency?
- reflects inadequate absorption and not poor intake
- lack of HCL (development of atrophic gastritis esp. in elderly)
- Lack intrinsic factor (defective gene of IF)
- impaired DNA synthesis
- defective proliferation of rapidly dividing cells (megalobasltic anaemia, glossitis, hypospermia.. etc)
