Metsbolism and metabolic disease

Question 1

Which vitamins are fat soluble and which are water soluble?

Answer 1

Fat soluble - A,D,E and K

All others are water soluble

Question 2

What are vitamins A,D,E and K synthesised from?

Answer 2

Isoprene units

Question 3

What are the only 2 vitamins that can be synthesised in the body?

Answer 3

D and K

Question 4

What is Vitamin A?

Answer 4

Umbrella term describing several components including retinol and retinal

Question 5

What are some sources of vitamin A?

Answer 5

• Broccoli
• Liver
• Sweet potato
• B-carotene from plants

Question 6

Vitamin A associated with the protein opsin forms what?

Answer 6

Rhodopsin

Question 7

Where is rhodopsin found?

Answer 7

Membrane discs of rod cells

Question 8

What other 4 opsins do humans have?

Answer 8

• Photopsins I, II and III found in cone cells

- Melanopsin found in photosensitive ganglion cells

Question 9

Describe the visual cycle

Answer 9

• 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

Question 10

Describe the biochemical mechanism of sight

Answer 10

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

Question 11

What is vitamin C otherwise known as?

Answer 11

ascorbic acid

Question 12

Why can’t humans synthesise vitamin C?

Answer 12

Because we have lost the last enzyme in the synthesis pathway

Question 13

What is vitamin C used for?

Answer 13

• collagen synthesis
• antioxidant
• metal chelator
• facilitates iron absorption from intestine

Question 14

Lack of vitamin C causes what disease?

Answer 14

Scurvy

Question 15

What are the symptoms of scurvy?

Answer 15

• Swollen, bleeding gums
• Pain in limbs
• Reddish bruise like spots
• Severe pain and bleeding inside joints

Question 16

What can occur is scurvy is left untreated?

Answer 16

Can enlarge the heart muscles causing cardiac bleeding

can result in death

Question 17

What is vitamin D?

Answer 17

Umbrella term for vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol)

Question 18

How is vitamin D3 synthesised?

Answer 18

In the skin, 7-dehydocholesterol is converted to D3 using UV light

Question 19

How is vitamin D3 activated?

Answer 19

Converted to 1,25(OH)2 vitamin D3 in liver or kidney

Question 20

Why do modern human need dietary vitamin D?

Answer 20

Clothed - less produced in skin

Question 21

What are the 2 major effects of Vitamin D?

Answer 21

• Uptake of calcium from intestine

- Release of calcium from bone

Question 22

What is the result of vitamin D deficiency?

Answer 22

• Rickets in children
  impeded growth and deformity of long bones
• Osteomalacia in adults
  milder condition
  diffuse body pains, muscle weakness and fragility of bones

Question 23

What is the treatment for Rickets and osteomalacia?

Answer 23

Administration of D3 or D2

Question 24

Where do humans get vitamin K from?

Answer 24

• Vitamin K from green plants

- Vitamin K2 from gut microorganisms

Question 25

What are the symptoms of vitamin K deficiency?

Answer 25

- Localisation of blood (haematomas) - Red or purple skin spots (petechiae) - Stomach pains - Risk of massive uncontrolled bleeding - Cartilage calcification

Question 26

What is Warfarin?

Answer 26

- Synthetic analogue to vitamin K

Question 27

What is Warfarin used for?

Answer 27

- Inhibits the formation of active prothrombin - Potent rodenticide - Drug for treating individuals at risk of excessive blood clotting

Question 28

What can be caused by a large excess of vitamin C and Vitamin A

Answer 28

- Excess of vitamin c can cause gastrointestinal problems | - Excess of vitamin A can cause foetal malformationd

Question 29

What is the overall reaction type of pyruvate to acetyl CoA and CO2 by the PDC?

Answer 29

Oxidative decarboxylation

Question 30

What are the 5 cofactors needed for the pyruvate dehydrogenase complex (PDC)

Answer 30

- Thiamine pyrophosphate (TPP) - Flavin adenine dinucleotide (FAD) - Coenzyme A (CoA-SH) - Nicotinamide adenine dinucleotide (NAD) - Lipoate

Question 31

What 4 cofactors have vitamins as vital components and what vitamins are they?

Answer 31

- Thymine/Vitamin B1 in TPP - Riboflavin/Vitamin B2 in FAD - Niacin/Vitamin B3 in NAD - Pantothenate/Vitamin B5 in CoA

Question 32

What are some characteristics of Thiamine/Vitamin B1?

Answer 32

- Water soluble - Only synthesised in bacteria, fungi and plants - Thiamine pyrophosphate is a coenzyme

Question 33

What is the overall reaction of the pyruvate dehydrogenase complex?

Answer 33

Pyruvate + CoA-SH + NAD+ --------------> Acetyl-CoA + NADH + CO2 PDC (E1+E2+E3) TPP Lipoate FAD

Question 34

What are the names of the 3 enzymes in the PDC?

Answer 34

E1 - pyruvate dehydrogenase E2 - dihydrolipoyl transacetylase E3 - dihydrolipoyl dehydrogenase

Question 35

What is the PDC reaction mechanism?

Answer 35

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

Question 36

What is pyruvate dehydrogenase complex deficiency with Leigh Syndrome?

Answer 36

- 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

Question 37

Who discovered vitamins and in what year?

Answer 37

Hopkins and Eijkman in 1929