PH1123 Vitamins and Coenzymes

Question 1

how does taking unnecessary vitamin supplements effect health ?

Answer 1

One in three women and one in four men in the UK take dietary supplements for health reasons. But a review of 14 trials of vitamin pills taken by 170,000 people found they increased the death rate by 6 per cent. While they offered no explanation as to what caused the deaths, they discovered that the supplements offered no protection against cancers of the gut.

The researchers, writing in The Lancet, estimate that for every one million people taking the supplements, 9,000 would die prematurely as a result. The figure takes account of the background level of premature death in the population.

Question 2

what’s an apoenzyme ?

Answer 2

the large protein molecule that forms the bulk of the enzyme molecule. In isolation it may be able to bind substrate but not able to catalyse its reaction

Question 3

Whats a co factor ?

Answer 3

non-protein molecule or metal ion that binds to the apoenzyme to form the holoenzyme. The cofactor may be bound at the active site or at a distant site on the apoenzyme.

Question 4

Whats a holoenzyme ?

Answer 4

Holoenzyme – the catalytically active form of the enzyme.

Question 5

Whats the substrate ?

Answer 5

Substrate – the substance upon which an enzyme acts

Question 6

Define a coenzyme

Answer 6

Definition: A non-protein organic compound, produced in living cells, which is involved in the activation of enzymes.
Co-substrates are altered during the course of the reaction and then dissociate from the enzyme. They are then regenerated by another enzymatic reaction.
Prosthetic groups remain bound to the enzyme but still need to be regenerated.

An enzyme is a protein that acts as a catalyst to increase the biochemical reaction rate without altering itself in the process, while a coenzyme is an organic non-protein molecule that is required by an enzyme to perform its catalytic activity.
Unlike enzymes, the coenzyme is often structurally altered during an enzyme-catalysed reaction.

Question 7

Whats the definition of a vitamin ?

Answer 7

Definition: General term for any of several organic substances essential for normal metabolic processes and which, when absent in the diet, produce deficiency states as THEY ARE NOT PRODUCED NATURALLY BY THE BODY.
Many coenzymes are synthesised from dietary precursors - these dietary precursors are often vitamins.

Question 8

describe the differences between water soluble and lipid soluble vitamins

Answer 8

WATER SOLUBLE

readily excreted via kidney in urine

 required daily (in small
amounts)

e.g. Vitamins B & C

LIPID SOLUBLE

stored in the body
(usually in liver)

excessive intake can
cause toxicity

e.g. Vitamins A, D, E & K

Question 9

state general information for B group vitamins

Answer 9

Originally thought to be a single vitamin but now understood to be multiple vitamins – all of which form coenzymes

Some can be synthesised within the body by intestinal flora (note: this is different to being produced by the body)

Question 10

State the sources, function and coenzyme produced by vitamin B1

Answer 10

Sources:
Found in cells therefore present in all whole natural foods e.g. whole cereal grains, beans, fruits and yeast

Coenzyme produced: Thiamine pyrophosphate (TPP)

Function:
Coenzyme to several enzymes in carbohydrate metabolism pathways (helping to release energy from food)
Also involved in conduction of action potentials in neurons and neuro-muscular transmission

Question 11

What is the deficiency state of vitamin B1 and in whom is it most prevalent?

Answer 11

Deficiency state
Prevalent in eastern Asia (white rice contains little thiamine) and in chronic alcoholics (severely malnourished). Athletes and pregnant/lactating women may require supplements (increased carbohydrate consumption)

Beriberi can affect different organ systems
Wet beriberi affects the cardiovascular system and presents with cardiac failure, dyspnoea and oedema

Dry beriberi affects the peripheral nervous system and presents with peripheral neuritis, paralysis and wastage. A severe form of dry beriberi is known as Wernicke–Korsakoff syndrome and is characterised by paralysis of eye movement, unusual movements and impaired mental function.

Question 12

State the sources, function and coenzymes produced by vitamin B2

Answer 12

Name: Vitamin B2 [A.K.A. riboflavin]

Sources:
Dairy products, eggs, green vegetables and almonds

Flavin mononucleotide (FMN)
Flavin adenine dinucleotide (FAD)

Function:
Heterocyclic system acts as a H acceptor (or donor)
Coenzymes act as prosthetic groups on a family of mainly oxidoreductase enzymes known as flavoproteins
Involved in the metabolism of fats, carbohydrates and proteins
Also acts as a coenzyme in the processing of other vitamins (e.g. conversion of vitamin B6 into its coenzyme)

Question 13

What is the deficiency state of vitamin B2 ?

Answer 13

Deficiency state
Rare in developed countries due to fortified foods but common in developing countries (due to malnutrition)
SYMPTOMS INCLUDE INFLAMMATION OF THE MOUTH AND LIPS (STOMATITIS) WHICH IS SIMILAR TO PELLAGRA BUT WITHOUT THE WIDESPREAD SKIN LESIONS (PELLAGRA SINE PELLAGRA)
It can also reduce iron absorption leading to anaemia with the size and haemoglobin content of red blood cells remaining normal (normochromic normocytic anaemia)

Question 14

State the sources, function and coenzymes produced by vitamin B3

Answer 14

Name: Vitamin B3 [A.K.A. nicotinamide (niacinamide); niacin (nicotinic acid)]

Sources:
Meat, fish and nuts
Nicotinamide also used in acne treatments

Coenzymes produced:
Nicotinamide adenine dinucleotide (NAD)
Nicotinamide adenine dinucleotide phosphate (NADP

Function:
Important in oxidoreductase enzyme reactions: NAD(P)+ is an oxidising agent whilst NAD(P)H is a reducing agent
NADPH is important in anabolic processes (e.g. lipid and nucleic acid synthesis) whilst NAD+ is vital to catabolic processes (e.g. metabolism of energy sources like fatty acids and glucose)

Question 15

What is the deficiency state of vitamin B3

Answer 15

Deficiency state
Body not entirely dependant on dietary intake as nicotinic acid can be produced from dietary tryptophan in vivo
Deficiency common in areas in which maize is the principal foodstuff (as it is low in both nicotinic acid and tryptophan)
Pellagra – characterised by ‘dermatitis, diarrhoea and dementia’.
Chronic alcoholics also at risk of deficiency

Question 16

What is the toxicity state of vitamin B3 ?

Answer 16

Toxicity state
Skin flushes, liver damage (mainly seen with niacin supplementation; nicotinamide may be given as alternative supplement)

Question 17

State the sources, function and coenzymes produced by vitamin B5

Answer 17

Name: Vitamin B5 [A.K.A. pantothenic acid]

Sources:
Dairy products, eggs, avocado, mushrooms
Present in the outer layers of whole grains- milling greatly reduces the pantothenic acid content

Coenzyme produced: coenzyme A

Function:
Coenzyme in the synthesis and oxidation of fatty acids
Involved in the oxidation of pyruvate as part of the Krebs cycle

Question 18

What is the deficiency state of vitamin B5 ?

Answer 18

Deficiency state

Extremely rare and as a result has not been studied thoroughly

Question 19

State the Name, sources, function and coenzymes produced by vitamin B6

Answer 19

Name: Vitamin B6 [A.K.A. pyridoxine, pyridoxal, pyridoxamine]

Sources:
Found in most foods of vegetable (pyridoxine) or animal (pyridoxal, pyridoxamine) origin
Interconvertible via their phosphates in vivo

Coenzyme produced: pyridoxal-5’-phosphate

Function:
Involved in tryptophan metabolism (vitamin B6 deficiency is a risk factor for vitamin B5 deficiency)
Also involved in the production of a number of neurotransmitters (e.g. dopamine, GABA)
Acts as a coenzyme for an extremely broad range of enzymes (approximately 4% of enzymes; >140 reactions)

Question 20

What is the deficiency state of vitamin B6 ?

Answer 20

Deficiency state
Rare as most diets contain adequate amounts and some is synthesised by intestinal flora
Results in disorders of CNS, skin and mucous membranes
Patients taking medicines such as isoniazid may benefit from increased intake due to increased excretion of pyridoxine

Question 21

What is the toxicity state of vitamin B6 ?

Answer 21

Toxicity state
Supplementation with high doses of vitamin B6 can lead to nerve damage (particularly in spinal ganglia) which manifests as pain/numbness in the extremities or in extreme cases difficulty with motor functions

Question 22

State the Name, sources, function and coenzymes produced by vitamin B7

Answer 22

Name: Vitamin B7 [A.K.A. biotin]

Sources:
Egg, avocado, yeast, fresh vegetables

Coenzyme produced: N/A [biotin acts as a coenzyme]

Function:
Required by several carboxylase enzymes that are involved in fatty acid synthesis, amino acid breakdown and glucose synthesis (gluconeogenesis)

Question 23

what is the deficiency state of vitamin B7 ?

Answer 23

Deficiency state(s)
Rare – severe deficiency never reported in healthy individuals eating a normal mixed diet
Presents with thinning hair, brittle nails, rashes and neurological symptoms
Pregnant/lactating women at risk of deficiency (clinical reason unknown)
Those eating lots of raw eggs are at risk due to avidin in the whites reducing the absorption of biotin

Question 24

State the Name, sources, function and coenzymes produced by vitamin B9

Answer 24

Name: Vitamin B9 [A.K.A. folic acid]

Sources:
Nuts, seeds, chickpeas, green vegetables
Folic acid is the vitamin that is most commonly added to ‘fortified’ foods such as flour

Coenzyme produced: tetrahydrofolate (THF)

Function:
THF is the coenzyme in enzymatic reactions that transfer hydroxymethyl (-CH2OH), formyl (-CHO) and methyl (-CH3) groups in a large number of reactions and significantly in the synthesis of amino acids and purine/pyrimidine bases in the formation of DNA

Question 25

What is the deficiency state of vitamin B9 ?

Answer 25

Deficiency state Patients with malignant disease or who are pregnant/breastfeeding are at risk of deficiency due to increased folic acid demand. A number of medications (e.g. methotrexate) interfere with folic acid processing and so create a risk of deficiency Folic acid deficiency during pregnancy is associated with low birth weight, premature birth and neural tube defects Supplements are therefore given in pregnancy, leukaemia and drug-induced folate deficiency Deficiency can cause megaloblastic anaemia (large red blood cells) due to faulty erythrocyte multiplication and maturation Supplementation with folic acid may mask vitamin B12 deficiency which leads to damage to the nervous system

Question 26

State the Name, sources, function and coenzymes produced by vitamin B12

Answer 26

Name: Vitamin B12 [A.K.A. cobalamin] Sources: Animal food sources (meat, fish, milk, eggs) Rare in common plant-based foods (some in fermented foods and seaweed) Coenzyme produced: adenosylcobalamin and methylcobalamin (the body converts hydroxocobalamin and cyanocobalamin from the diet into these active forms) Function: Acts as a cofactor for methionine synthase which is involved in the production of THF from folic acid Also acts as cofactor in molecular rearrangement reactions (e.g. metabolism of branched-chain amino acids) – particularly in the central nervous system

Question 27

What is the deficiency state of Vitamin B12 ?

Answer 27

Deficiency state Deficiency cause pernicious anaemia – megaloblastic anaemia plus gastrointestinal (diarrhoea, loss of bladder control) and neurological symptoms (seizures, degeneration of spinal cord) Folic acid supplementation can reverse the megaloblastic anaemia but will not reverse the other symptoms Care must be taken with anaemic patients to balance intake of folic acid, cobalamin and iron

Question 28

State the Name, sources, function and coenzymes produced by vitamin C

Answer 28

Name: Vitamin C [A.K.A. ascorbic acid] Sources: Citrus fruits, guava, kiwi, broccoli, and Brussels sprouts First ever clinical trial used citrus juice vs. scurvy (1747) Coenzyme produced: N/A [ascorbic acid acts as a cofactor] Function: Most powerful reducing agent known to occur naturally in living tissue Acts as a cofactor in the hydroxylation of proline to hydroxyproline (creating more OH groups for H-bonding) which gives the triple helix of collagen its strength Ascorbic acid is important due to its ability to maintain metal ions (also cofactors) in the correct ionic state within an enzyme’s active site (e.g. Fe2+ in the active site of prolyl hydroxylase) It also acts as cofactor in steroid synthesis, noradrenaline production and the conversion of folic acid to THF It also has an important independent role within the body as an antioxidant- donating electrons to limit the damage caused by free radicals and oxidative species It is also involved in immune system regulation (especially during infection)

Question 29

What is the deficiency state of vitamin C?

Answer 29

Deficiency state Scurvy is characterised by swollen gums, bruising, haemorrhage, bone fracture, loose teeth, poor wound healing and anaemia Supplements may benefit those not following a balanced diet (elderly, infirm), diabetics, pregnant and lactating women, heavy drinkers and smokers

Question 30

What is the toxicity state of vitamin C ?

Answer 30

Toxicity state | Stomach complaints

Question 31

State the Name, sources, function and coenzymes produced by vitamin A

Answer 31

Name: Vitamin A [A.K.A. retinol] Sources: Cod liver oil, butter, cheese, milk Retinol can be synthesised from carotenoids (found in carrots and tomatoes) Coenzyme produced: N/A [retinol does not form a coenzyme] Function: Retinol is converted into retinal and retinoic acid in the body Retinal is further converted to 11-cis-retinal (using NADP+ as a coenzyme) which is a photosensitive prosthetic group essential for normal function of the retina The retinal molecule undergoes isomerisation in the presence of a photon of the correct wavelength of light It is regenerated via the RPE65 enzyme so that it can be used to detect light again Retinoic acid is required for normal embryonic development, growth, development, immune system function and the maintenance of epithelial tissue (including skin- retinoic acid used as psoriasis/acne treatment)

Question 32

What is the deficiency state of vitamin A ?

Answer 32

Deficiency state Still widespread in developing world. Symptoms include night blindness, dry/ hyperkeratotic skin, skin infection, corneal damage and blindness. Supplements may be required in breast feeding women to compensate for infant’s supply and in patients unable to absorb or store lipids

Question 33

What is the toxicity state of Vitamin A ?

Answer 33

Toxicity state Toxicity to unborn children (C/I using retinoic acid in pregnancy) Hypervitaminosis A – excessive intake (usually supplements or diet (esp. liver) can lead to liver damage, bone pain, vision changes and death

Question 34

State the Name, sources, function and coenzymes produced by vitamin D

Answer 34

Name: Vitamin D [A.K.A. calciferol] Sources: Ergocalciferol is found in fungi sources (e.g. mushrooms) and cholecalciferol is found in animal sources (e.g. fatty fish, cod liver oil, egg yolk) The body is not entirely dependent on dietary intake as vitamin D3 is formed under UV light from provitamin precursors (7-dehydrocholesterol) in the skin Coenzyme produced: N/A [calciferol does not form a coenzyme] Function: Calciferol is converted into calcifediol in the liver before being further altered in the kidney to produce calcitriol Calcitriol stimulates synthesis of specific proteins that act as Ca2+ carriers in bone and intestine increasing absorption of dietary Ca2+ and release of Ca2+ from bone (PO4- passively accompanies the Ca2+ movements) Calcitriol maintains Ca2+ and PO4- at sites of new bone formation therefore is essential for proper formation of the skeleton

Question 35

What is the deficiency state of vitamin D ?

Answer 35

Deficiency state Calciferol deficiency leads to rickets in children- characterised by distortion of the long bones of the legs and bones of the pelvis and spine Calciferol deficiency in adults leads to osteomalacia (bone softening) Rate of synthesis of vitamin D in the skin depends on exposure to UV light therefore night workers and miners traditionally prone to deficiency Rate of synthesis of vitamin D in the skin also depends on skin pigmentation. Melanin protects skin cells by preventing UV light penetration into the skin- this reduces the efficiency of the conversion of 7-dehydrocholesterol

Question 36

What is the toxicity state of vitamin D ?

Answer 36

Toxicity state | Hypercalcaemia  calcium deposits in organs (e.g. kidneys, liver, heart), anorexia, insomnia, abnormal bone formation

Question 37

State the Name, sources, function and coenzymes produced by vitamin E

Answer 37

Name: Vitamin E [A.K.A. the tocopherols and tocotrienols] Sources: Vegetable oils (e.g. sunflower oil, rapeseed oil and palm oil) Coenzyme produced: N/A [tocopherols/tocotrienols do not form coenzymes] Function: Act as a fat-soluble antioxidant – they are particularly important in protecting cell membranes from oxidative damage by free radical species Also involved in smooth muscle growth and the maintenance of nerves

Question 38

What is the deficiency state of vitamin E ?

Answer 38

``` Deficiency state(s) Usually due to malabsorption of fat rather than lack of dietary intake Symptoms include nerve damage and haemolytic anaemia – due to oxidative damage to red blood cells ```

Question 39

What is the toxicity state of vitamin E ?

Answer 39

Toxicity state | Antagonises vitamin K- leading to risk of bleeding

Question 40

State the Name, sources, function and coenzymes produced by vitamin K

Answer 40

Name: Vitamin K [A.K.A. phytomenadione (K1), menaquinone (K2)] Sources: Leafy green vegetables (e.g. spinach, cabbage, kale) contain high levels of phytomenadione. Menaquinone is found in eggs, meat and dairy products. Intestinal flora can convert phylloquinone into menaquinone Coenzyme produced: N/A [phytomenadione acts as a cofactor] Function: Acts as a cofactor in reactions that add a second carboxylic acid group onto the glutamate residues of a number of proteins to form a gamma-carboxyglutamate (Gla) residue This is important in the formation of coagulation factors II (prothrombin), VII, IX, and X in the liver Also involved in the production of anticoagulant proteins C and S and protein Z Warfarin inhibits phytomenadione’s effects on the coagulation to mediate its clinical effect

Question 41

What is the deficiency state of vitamin k ?

Answer 41

Deficiency state Rarely due to lack of dietary intake Liver damage (e.g. alcoholics) and medication (e.g. anticoagulants) can lead to deficiency Symptoms include anaemia, bruising and bleeding at the mucosal membranes (e.g. gums, nose)

Question 42

What is the toxicity state of vitamin K ?

Answer 42

Toxicity state Unlike most fat-soluble vitamins, not stored in great quantities in the liver Therefore, toxicity is not seen with higher doses of vitamin K1 or K2 in otherwise healthy people