Metsbolism and metabolic disease Flashcards
Which vitamins are fat soluble and which are water soluble?
Fat soluble - A,D,E and K
All others are water soluble
What are vitamins A,D,E and K synthesised from?
Isoprene units
What are the only 2 vitamins that can be synthesised in the body?
D and K
What is Vitamin A?
Umbrella term describing several components including retinol and retinal
What are some sources of vitamin A?
- Broccoli
- Liver
- Sweet potato
- B-carotene from plants
Vitamin A associated with the protein opsin forms what?
Rhodopsin
Where is rhodopsin found?
Membrane discs of rod cells
What other 4 opsins do humans have?
- Photopsins I, II and III found in cone cells
- Melanopsin found in photosensitive ganglion cells
Describe the visual cycle
- Cis retinal associates with opsin to form rhodopsin
- Absorbs a ‘green/blue’ photon: light induced isomerism to trans retinal initiates light perception and subsequent dissociation of opsin and pigment
- Elicits a signalling cascade via interaction with transducin
Describe the biochemical mechanism of sight
1) Light induces conformational change and dissociation
2) Transducin binds GTP
3) Diminishes cGMP levels by elevating phosphodiesterase activity
4) Closes Na channels, resulting in hyperpolarisation of the photoreceptor cell
5) Diminishes release of glutamate into the synapse: This depolarises the inter connecting (bipolar) neuron, which stimulates the ganglionic neuron
What is vitamin C otherwise known as?
ascorbic acid
Why can’t humans synthesise vitamin C?
Because we have lost the last enzyme in the synthesis pathway
What is vitamin C used for?
- collagen synthesis
- antioxidant
- metal chelator
- facilitates iron absorption from intestine
Lack of vitamin C causes what disease?
Scurvy
What are the symptoms of scurvy?
- Swollen, bleeding gums
- Pain in limbs
- Reddish bruise like spots
- Severe pain and bleeding inside joints
What can occur is scurvy is left untreated?
Can enlarge the heart muscles causing cardiac bleeding
can result in death
What is vitamin D?
Umbrella term for vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol)
How is vitamin D3 synthesised?
In the skin, 7-dehydocholesterol is converted to D3 using UV light
How is vitamin D3 activated?
Converted to 1,25(OH)2 vitamin D3 in liver or kidney
Why do modern human need dietary vitamin D?
Clothed - less produced in skin
What are the 2 major effects of Vitamin D?
- Uptake of calcium from intestine
- Release of calcium from bone
What is the result of vitamin D deficiency?
- Rickets in children
impeded growth and deformity of long bones - Osteomalacia in adults
milder condition
diffuse body pains, muscle weakness and fragility of bones
What is the treatment for Rickets and osteomalacia?
Administration of D3 or D2
Where do humans get vitamin K from?
- Vitamin K from green plants
- Vitamin K2 from gut microorganisms
What are the symptoms of vitamin K deficiency?
- Localisation of blood (haematomas)
- Red or purple skin spots (petechiae)
- Stomach pains
- Risk of massive uncontrolled bleeding
- Cartilage calcification
What is Warfarin?
- Synthetic analogue to vitamin K
What is Warfarin used for?
- Inhibits the formation of active prothrombin
- Potent rodenticide
- Drug for treating individuals at risk of excessive blood clotting
What can be caused by a large excess of vitamin C and Vitamin A
- Excess of vitamin c can cause gastrointestinal problems
- Excess of vitamin A can cause foetal malformationd
What is the overall reaction type of pyruvate to acetyl CoA and CO2 by the PDC?
Oxidative decarboxylation
What are the 5 cofactors needed for the pyruvate dehydrogenase complex (PDC)
- Thiamine pyrophosphate (TPP)
- Flavin adenine dinucleotide (FAD)
- Coenzyme A (CoA-SH)
- Nicotinamide adenine dinucleotide (NAD)
- Lipoate
What 4 cofactors have vitamins as vital components and what vitamins are they?
- Thymine/Vitamin B1 in TPP
- Riboflavin/Vitamin B2 in FAD
- Niacin/Vitamin B3 in NAD
- Pantothenate/Vitamin B5 in CoA
What are some characteristics of Thiamine/Vitamin B1?
- Water soluble
- Only synthesised in bacteria, fungi and plants
- Thiamine pyrophosphate is a coenzyme
What is the overall reaction of the pyruvate dehydrogenase complex?
Pyruvate + CoA-SH + NAD+ ————–> Acetyl-CoA + NADH + CO2
PDC (E1+E2+E3)
TPP
Lipoate
FAD
What are the names of the 3 enzymes in the PDC?
E1 - pyruvate dehydrogenase
E2 - dihydrolipoyl transacetylase
E3 - dihydrolipoyl dehydrogenase
What is the PDC reaction mechanism?
1) pyruvate reacts with bound TPP of E1, undergoing decarboxylation to hydroxyethyl derivative
2) Hydroethyl is oxidised to the level of a carboxylic acid (acetate). The 2 electrons removed reduce -S-S- of lipoyl group on E2 to 2 thiol (-SH) groups
3) Transesterification in which the -SH group of CoA replaces the -SH group of E2 to yield acetyl-CoA and the fully reduced (dithiol) form of the lipoyl group
4) E3 promotes transfer of 2 hydrogen atoms from reduced lipoyl groups of E2 to FAD of E3, restoring the oxidised for of the lipoyl group of E2
5) Reduced FADH2 of E3 transfers a hydride ion to NAD+, forming NADH - enzyme complex now ready for another cycle
What is pyruvate dehydrogenase complex deficiency with Leigh Syndrome?
- PDHC activity significantly lower at low TPP concentrations
- Decrease in affinity of PDHC for TPP
- Sequencing of X linked PDHC Ela subunit revealed a C to G point mutation resulting in a substitution of glycine for arginine
Who discovered vitamins and in what year?
Hopkins and Eijkman in 1929
