Vitamin C Flashcards
Talk about the structure of Vitamin C
It is a 6c lactone
Reduced form - ascorbic acid
Oxidised form - ascorbyl radical, dehydroascorbic acid (fully oxidised form)
Biological function of Vitamin C?
Acceptor and donor of e-
What is oxidised form of Vitamin C called?
Ascorbyl radical - fully oxidised form called dehydroascorbic acid
Explain synthesis of Vitamin C
- It is synthesised from glucose by plants
- Some animals synthesise in their liver, kidney
- Humans lost ability to synthesise it 30-40m years ago
- because of a mutation in the gulonolactone oxidase gene, which means we cant convert l-gulonlactone into 2 ketogulonlactone
- Proposed that we lost it because we had lots of fruits in the diet making it redundant - biological advantage? (during global cooling - to prevent fat burn)
Sources of Vitamin C
Fruits: (1cup)
Peach- 236
Papaya-188
Orange Juice-124
Veg: (raw- 1 cup)
Red pepper - 283
Green pepper - 123
Hot chilli pepper- 109
Animal sources: (mg/100g) Beluga whale 38 - raw Lamb liver - 12 - fried Oyster 30 - raw Milk - 2mg/100ml
UK DRV for Vitamin C?
40-45mg/day
What is relationship b/w dietary intake of vit c intake plasma levels?
Increase intake in vit C causes increase plasma concentrations till intakes of 100-200mg /day blood
(after-which plasma levels plateau at around 70-80uM)
-above that ascorbic acid levels do not alter.
What is relationship b/w
dietary intake of vit c and tissue concentrations?
There is a steep rise in tissues vit c levels as intake levels increase to 100 mg/day
-thereafter tissue ascorbic acid levels plateau.
- Data indicates that relative to dietary intake, tissue ascorbic acid concentrations are also tightly controlled. —Why tight control over vitamin C
levels in blood and tissues occurs is still unclear
Talk about tight control of Vitamin C levels in
blood/tissues
- Mediated by kidney and gut
- Kidney is responsible for tight control of vitamin C levels
- Once Vit C levels cross 60mg/day it starts to appear in urine
Talk about uptake and absorption of vit c
-Absorption happens in SI
-Vit C water soluble so needs mediator for absorption into lipid bilayer of plasma membrane
-It is absorbed from intestinal lumen to enterocyte as ASCORBIC ACID via Na Dependant Vit C transporter - SVCT 1
-It enters Portal circulation
-Then transported by SVCT 1 to liver cells
-From liver cells transported to other tissues by SVCT 2
SVCT1 is a low affinity/high capacity Asc transporter
whereas SVCT2 is a high affinity/low capacity transporter.
-SVCT1 can operate over a wide Asc concentration range such as those found in the gut, kidney and liver,
-whereas Svct2 operates over a lower concentration range, ensuring efficient extraction and delivery of the vitamin from blood into tissues.
-Once dietary conc ↑ above 200mg/day - SVCT 1 is saturated in gut - limited absorption
-Once kidney Vit C level ↑ above 60mg/day - SVCT 1 in kidney saturated- limited reabsorption
-SVCT1 is most likely responsible for tight control of vitamin C concentrations in blood and tissues
Talk about alternate route of VIt C Absorption
- GLUT 1-4 can transport vit C into cell when it is in oxidised form- dehydroascorbic acid (DHA)
- THis is because DHA structurally similar to Glucose
- Once inside cell - it is reduced to ascorbic acid (active form) by internal mechanism like glutathione
- This process is called ascorbate recycling
- It is a recovery pathway to maintain vitamin C levels in tissues under oxidizing conditions
Why do diabetics have low ascorbate levels?
-hyperglycemic inhibition of DHA uptake via GLUTs
-Results in low grade tissue scurvy
-Controversial - Concentrations of DHA in blood are v low (1-2 uM) - it’s not clear if the value is real or an assay artifact, caused by Asc oxidation during sample handling. -Blood glucose levels are also in mM range, whereas DHA, if it exist at all in blood, is in the uM range
DHA uptake by GLUTs would therefore be blocked by glucose.
-Recycling may still occur but under very specific localized oxidizing conditions, like in intestinal lumen during digestion/absorption of foods.
What is ascorbate recycling?
- GLUT 1-4 can transport vit C into cell when it is in oxidised form- dehydroascorbic acid (DHA)
- THis is because DHA structurally similar to Glucose
- Once inside cell - it is reduced to ascorbic acid (active form) by internal mechanism like glutathione
- This process is called ascorbate recycling
- It is a recovery pathway to maintain vitamin C levels in tissues under oxidizing conditions
Why do diabetics have low ascorbate levels?
-hyperglycemic inhibition of DHA uptake via GLUTs
-Results in low grade tissue scurvy
-Controversial - Concentrations of DHA in blood are v low (1-2 uM) - it’s not clear if the value is real or an assay artifact, caused by Asc oxidation during sample handling. -Blood glucose levels are also in mM range, whereas DHA, if it exist at all in blood, is in the uM range
DHA uptake by GLUTs would therefore be blocked by glucose.
-Recycling may still occur but under very specific localized oxidizing conditions, like in intestinal lumen during digestion/absorption of foods.
What are biochemical functions of Vit C?
Used for enzymatic and non enzymatic reactions
Enzymatic reactions:
- (3) Collagen hydroxylation (e.g. Prolyl 4 –hydroxylase)
Stabilizes collagen matrices
- (2) Carnitine synthesis ( e.g. Butyrobetaine hydroxylase)
Fatty acid metabolism (ATP) - Dopamine to Noradrenaline (Dopamine hydroxylase)
Sympathetic neurotransmitter, HR, glucose metabolism, blood flow, fight /flight - Amidation of hormones (e.g. peptidylglycine monoxygenase)
50% of human peptides require amidation for biological activity (receptor recognition) - Tyrosine catabolism (hydroxyphenylpyruvate dioxygenase)
- Hydroxylation (degradation) hypoxia inducible factor ( Asparaginyl hydroxylase)
