Vitamin C biosynthesis Flashcards
The inability of humans to synthesise ascorbate is in the
L-gulonolactone oxidase
the last enzyme in the pathway
Ascorbate synthesis pathways in animals and plants are
not the same
The precursor to all ascorbate biosynthesis is
an aldonic acid lactone
derived from uronic or aldonic acid
Ascorbate synthesis pathway in animals
L-Gulonolactone + O2 –> Asc and H202
catalysed by Gulonolactone oxidase
GULO is ER associated
Ascorbate synthesis pathway in plants
L-Galactonolactone + CytC ox –> Asc + CytC red
catalysed by Galactonolactone dehydrogenase
GALD is found in mitochondrial complex 1
What is the possible reason that ascorbate biosynthesis may have been lost in some animals?
GULO (gulonolactone oxidase) produces H202 during ascorbate synthesis
Where does L-Galanolactone come from?
L-galactose is the precursor for L-galactonolactone
L-gal is rare - most sugars are metabolised in D conformation
L-galactose to L-galactonolactone reaction catalysed by NAD+ (NAD dependent dehydrogenase)
At what stage is ascorbate synthesis controlled in plants?
The 3/4th step by GDP-L-gal phosphorylase
What affects ascorbate concentration in plants?
The VTC2 gene and the rate of ascorbate breakdown
transcription of the vtc2 gene is promoted by light and repressed by ascorbate
In plants ascorbate is essential for
seedling growth and resistance to ROS
In humans, ascorbate deficiency results in
defects in collagen (scurvy)
collagen is an extracellular protein with a critical structural role in tissues
collagen contains hydroxyproline which is formed by hydroxylation of proline residues by prolyl hydroxylase. This enzyme is a member of the large 2-oxoglutarate dependent dioxygenases (2-ODD) family which require ascorbate to function (used in repair of the enzyme - FeIV cannot be reduced back to FeII)
Ascorbate deficiency can influence a range of processes because 2ODDs are involved in a large range of reactions
- prolyl hydroxylase
- carnitine synthesis
- hormones - noradrenaline and dopamine
- O2 sensing with HIF (hypoxia inducible factor)
- epigenetic regulation (methylations of lysine)
Ascorbate improves iron uptake by reducing
Fe3+ to Fe2+ (more soluble)
Ascorbate has been shown to be both an anti oxidant and a pro oxidant
high doses can cause DNA damage due to the Fenton Reaction:
H202 + Fe2+ –> .OH + OH- + Fe3+
high doses delivered to tumours selectively kills cancer cells due to high Fe availability
The REICHSTEIN PROCESS (industry synthesis of ascorbate) is essential but not environmentally friendly because
it uses high temps and pressures and organic solvents
there is one bacterial step: gluconobacter reduces sorbitol to sorbose
D-Glu > D-sorbitol > L-sorbose > Diacetone-L-sorbose > 2 keto-L-gulonic acid > 2klg methyl ester > L ascorbic acid
