lecture 14: vitamin C Flashcards
ascorbic acid
6 carbon lactone synthesized from glucose
most mammals synthesize in the liver, humans unable
why can’t humans synthesize vitamin C
we lack gulonolactone oxidase, the terminal enzyme in the biosynthetic pathway of ascorbic acid
ascorbate absorption
sodium-dependent process via SVCTs - highly specific
absorption of dehydroascorbic acid
sodium independent process
GLUT 1,3,4 transport with high affinity, due to structural similarities of dehydroascorbic acid and glucose
once absorbed, reduced to ascorbate in enterocytes
excess vitamin C supplements
plasma levels saturated at 200-400 mg daily
vitamin c distributes into general circulation
reabsorbed after filtering in the kidneys
when it is saturated, excess vitamin C is excreted in the urine
ascorbyl radical
formed by partial oxidation of ascorbate, can be reduced to ascorbate
two radicals react with eachother in a non-enzymatic dismutation reaction (one becomes fully oxidized, one becomes reduced)
reacts poorly due to resonance stabilization, ideal electron donor and strong antioxidant
ascorbate recycling
dehydroascorbic acid rapidly reduced in vivo, either by one electron reduction to ascorbyl radical or [2 electron reduction to ascorbate] - ascorbate recycling
NADPH
electron donating agent for dehydroascorbic acid reduction
iron absorption
vitamin c supplements increase non-heme iron absorption, reduces Fe3+ to Fe2+ to form an absorbable iron-ascorbic acid complex
non enzymatic functions of ascorbate
reductant
recycling of tetrahydrobioprotein
antioxidant
THB
cofactor for many enzymes, including eNOS (produces nitric oxide - relaxation of smooth muscle cells)
ascorbate maintains or increases THB levels by reduction of oxidized THB
increase eNOS activity, decrease BP
vitamin C as antioxidant
free radical scavenger, reduces harmful biological oxidants
ascorbyl radical is stable due to delocalized electrons
first line of antioxidant defense in extracellular fluids, prevents lipid peroxidation
the antioxidant network
group of antioxidants work together to maintain reduced forms of vitamins C and E (ex. ascorbate can reduce one-electron oxidation of a-tocopherol)
GSH can act as electron donor to reduce dehydroascorbic acid
monooxygenase
incorporate single oxygen atom (O) into a substrate
require 2 copper atoms in active site, reduced by ascorbate, receive 1 e from each of 2 ascorbate
2 ascorbyl radicals dismutate
norepinepherine synthesis: dopamine B-hydroxylase
Peptide Hormones: Peptidylglycine α-Amidating Monooxygenase
dioxygenase
incorporate O2
most require a-ketogluterate as a co-substrate
use iron in active sites
collagen and carnitine synthesis
cross-linking of peptides in collagen
collagen synthesis
cross-linking of peptides in collagen
hydroxylase dioxygenases have specific binding sites for ascorbate
ascorbate keeps iron reduced in the reactive center (replenishes electrons)
if polypeptide substrate is limiting, enzyme catalyzes uncoupled decarboxylation > oxidation of iron center, can only be reduced with another ascorbate
L-carnitine
zwitterionic amino acid required to transfer long-chain FAs into mitochondria for B-oxidation and ATP synthesis > vitamin C deficiency causes fatigue
CPT1 Transfers FA, linked to carnitine
impaired carnitine biosynthesis
fatigue - early symptom of vitamin c deficiency
scurvy
vitamin C deficiency
symptoms like hemorrhaging, joint pain, bleeding under skin, etc related to loss of prolyl and lysyl hydroxylase activity for collagen biosynthesis
dismutation reaction of ascorbyl radicals
two ascorbyl radicals react together so one is reduced to ascorbate, other one oxidized to dehydroascorbic acid
After experiencing low energy for an extended time, your friend was diagnosed with having iron-deficiency anemia. It was recommended that they take an iron supplement for the next few months. You suggest taking a vitamin C supplement along with the iron supplement. When your friend ask you why, what do you say?
Vitamin C strongly enhances iron absorption by reducing dietary ferric Fe3+ iron to ferrous Fe2+ iron. It forms an absorbable iron-ascorbic acid complex.
Consider the symptoms of scurvy. Relate three of these symptoms to ascorbate’s function as a cofactor for enzymatic reactions.
Ascorbate works as a cofactor with hydroxylases for collagen synthesis - health of teeth, hair, and joints
symptoms: teeth, coiled hair, and arthralgias (joint pain)
Plays a role in carnitine synthesis - fatigue
why is it helpful that vitamin C is “middle of the road” as a reducing agent?
They can become reduced and reduce many strong biological oxidizers
Better move between oxidized and removed state – we want to be able to reduce vitamin C again
