lecture 14: vitamin C

Question 1

ascorbic acid

Answer 1

6 carbon lactone synthesized from glucose

most mammals synthesize in the liver, humans unable

Question 2

why can’t humans synthesize vitamin C

Answer 2

we lack gulonolactone oxidase, the terminal enzyme in the biosynthetic pathway of ascorbic acid

Question 3

ascorbate absorption

Answer 3

sodium-dependent process via SVCTs - highly specific

Question 4

absorption of dehydroascorbic acid

Answer 4

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

Question 5

excess vitamin C supplements

Answer 5

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

Question 6

ascorbyl radical

Answer 6

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

Question 7

ascorbate recycling

Answer 7

dehydroascorbic acid rapidly reduced in vivo, either by one electron reduction to ascorbyl radical or [2 electron reduction to ascorbate] - ascorbate recycling

Question 8

NADPH

Answer 8

electron donating agent for dehydroascorbic acid reduction

Question 9

iron absorption

Answer 9

vitamin c supplements increase non-heme iron absorption, reduces Fe3+ to Fe2+ to form an absorbable iron-ascorbic acid complex

Question 10

non enzymatic functions of ascorbate

Answer 10

reductant
recycling of tetrahydrobioprotein
antioxidant

Question 11

THB

Answer 11

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

Question 12

vitamin C as antioxidant

Answer 12

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

Question 13

the antioxidant network

Answer 13

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

Question 14

monooxygenase

Answer 14

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

Question 15

dioxygenase

Answer 15

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

Question 16

collagen synthesis

Answer 16

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

Question 17

L-carnitine

Answer 17

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

Question 18

impaired carnitine biosynthesis

Answer 18

fatigue - early symptom of vitamin c deficiency

Question 19

scurvy

Answer 19

vitamin C deficiency

symptoms like hemorrhaging, joint pain, bleeding under skin, etc related to loss of prolyl and lysyl hydroxylase activity for collagen biosynthesis

Question 20

dismutation reaction of ascorbyl radicals

Answer 20

two ascorbyl radicals react together so one is reduced to ascorbate, other one oxidized to dehydroascorbic acid

Question 21

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?

Answer 21

Vitamin C strongly enhances iron absorption by reducing dietary ferric Fe3+ iron to ferrous Fe2+ iron. It forms an absorbable iron-ascorbic acid complex.

Question 22

Consider the symptoms of scurvy. Relate three of these symptoms to ascorbate’s function as a cofactor for enzymatic reactions.

Answer 22

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

Question 23

why is it helpful that vitamin C is “middle of the road” as a reducing agent?

Answer 23

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