Vitamin C Flashcards
vitamin C aka
ascorbic acid or ascorbate
ascorbic acid (ascorbate) is synthesize from __ by many animals in __ or __
ascorbic acid (ascorbate) is synthesize from glucose by many animals in liver or kidney
is ascorbic acid produced by humans?
NO
2 food forms of vit C present in foods
ascorbic acid (AA)
dehydroascorbic acid (DHA)
best sources of vit c
fruits and veggies
other sources of vit c
animal organs (liver, kidney, brains)
__% AA, __% DHA
80-90% AA, 10-20% DHA
common sources of vit C
camu berry
tomato
peppers
tolerable upper limit (UL) is __ based on adverse effects of __
tolerable upper limit (UL) is 2 g/day based on adverse effects of osmotic diarrhea
can you reach UL from dietary vit C alone
no, it is only caused by excess supplementatin
excess vitamin c cause increased excretion of __ and __ which may increase __ formation
excess vitamin c cause increased excretion of oxalate and uric acid which may increase kidney stone formation
contraindications: people with __, __ anemia, or __ should aboid ascorbate supplements
contraindications: people with hemochromatosis, sideroblastic anemia (heme deficiency even with adequate iron), or thalassemia major (excess iron) should aboid ascorbate supplements
ascorbic acid acts as an __ (__ agent) and reacts with __
ascorbic acid acts as an electron donor (reducing agent) and reacts with oxidants
ascorbic acid can donate __ electrons
its free radical form is __
ascorbic acid can donate 2 electrons
its free radical form is stable
where is vit c absorbed
ileum and jejunum
2 methods of vit C absorption (overviews)
- ascorbate is coupled to sodium and transported directly by SVCT (sodium-dependent vit C transporter)
- GLUT requires extracellular oxidation of ascorbate to DHA
SVCT mechanism
- ascorbic acid goes through SVCT with NA+ and enters cell (against the gradient)
- Na+ leaves through ATPase
SVCT type of transporter
symporter: secondary active
why use SVCT and waste ATP
bc ascorbic acid is scarce in nature, so we must take advantage of it when available
vit C GLUT transport mechanism
- Asc –> DHA
- DHA is similar to glucose –> goes through GLUT into enterocyte
- enterocyte produces Asc
GLUT type of transport
facilitated diffusion
GLUT 1, 2, and 3 regulation
glucose
competitive inhibition
GLUT 4 regulation
insulin sitmulates
GLUT 1, 2, 3 location
osteoblasts
muscle
intestinal cells
GLUT 4 location
adipose
muscle cells
SVCT1 location
liver epithelial
intestine
kidney
SVCT 1 regulation
ascorbate: feedback inhibition of SVCT expression
more ascorbate absorbed, less activity of SVCT
SVCT2 location
broad distribution (brain, retinal, and placenta cells)
SVCT1 knockout
total loss of ascorbate resorption in kidneys BUT intestinal absorption is unchanged
SVCT2 knock out
severe ascorbate deficiency in tissues
KO IS LETHAL
mice die at birth
__ transporters must exist, but remain unidentified
efflux transporters must exist, but remain unidentified
as more ascorbate is absorbed, __ has __ activity
__ feedback
as more ascorbate is absorbed, SVCT1 has less activity
negative feedback
resorption of ascorbate in renal tubules by SVCT1 carrier is __
resorption of ascorbate in renal tubules by SVCT1 carrier is saturable
at vit C intakes of above __mg, all vit C is usually __
at vit C intakes of above 500 mg, all vit C is usually excreted
ascorbate in blood is __ soluble and free in __
ascorbate in blood is water soluble and free in plasma
tissue concentrations of ascorbate are __ than plasma levels
SO, ascorbate is actively transported __ a gradient into cells via a transporter
tissue concentrations of ascorbate are way higher than plasma levels
SO, ascorbate is actively transported against a gradient into cells via a transporter
white blood cells have a concentration of ascorbate that is up to __ times __ than plasma
white blood cells have a concentration of ascorbate that is up to 80 times higher than plasma
RBC and WBC uptake (via GLUT1 and GLUT3) and transport __ in circulation
RBC and WBC uptake (via GLUT1 and GLUT3) and transport DHA in circulation
degradative oxidation of ascorbate occurs primarily in __ but also to some extent in __
degradative oxidation of ascorbate occurs primarily in liver but also to some extent in kidneys
oxalic acid is found mainly in
spinach, but also lots of other foods
oxalic acid acts as a magnet for __ molecules (like __)
oxalic acid acts as a magnet for positively charged molecules (like Ca, Fe, Zn)
degradation: vit C is __ to DHA, then destroyed by __
degradation: vit C is oxidized to DHA, then destroyed by opening the ring
ascorbate enzymatic role
reducing agent, iron and copper containing enzymes
ascorbate non-enzymatic role
anti-oxidant and, possibly, pro-oxidant (by reducing free Fe and Cu ions)
2 non-enzymatic mechanisms of ascorbate
- antioxidant (free radical quenching)
- potential functions (pro-oxidant, ROS formation)
enzymatic mehcanisms of ascorbate (6)
- collagen synthesis (structural)
- carnitine synthesis (metabolic energy)
- catecholamine synthesis (hormonal)
- peptide amidation (ie vasopressin)
- epigenetic regulation (DNA and histone methylation)
- transcriptional regulation (ie HIF)
ascorbate in collagen synthesis role:
ascorbate reduces heme iron (ferric –> ferrous)
this restores enzyme activity
what enzyme activity is restored by ascorbate in collagen synthesis
prolyl hydroxylase
in collagen synthesis, ascorbate __ iron3+ to __
in collagen synthesis, ascorbate reduces iron3+ to iron2+
vit C is essential for __ synthesis
vit C is essential for carnitine synthesis
carnitine can be acquired from __ or synthesized from __ and __
carnitine can be acquired from diet or synthesized from lysine and methionine
ascorbate’s role in __ synthesis explains the first sign of vit C deficiency: __
ascorbate’s role in carnitine synthesis explains the first sign of vit C deficiency: fatigue
scurvy is associated with high circulating levels of __ and excretion of high levels of __
scurvy is associated with high circulating levels of tyrosine and excretion of high levels of 4-hydroxyphenyl pruvate
premature infants also have high levels of __ and excretion of high levels of __
__ fixes this issue
premature infants also have high levels of tyrosine and excretion of high levels of 4-hydroxyphenyl pruvate
ascorbate fixes this issue
alkaptonuria is a mutation that inactivates __
this causes __ to accumulate in __ and turn it __ color
alkaptonuria is a mutation that inactivates homogentisate dioxygenase
this causes homogentisate to accumulate in urine and turn it black color
depleted ascorbate prevents us from making __ and __
depleted ascorbate prevents us from making catecholamines and dopamine
epinephrine and norepinephrine are synthesized in __ and __
synthesis occurs in __ compartments
epinephrine and norepinephrine are synthesized in neurons and adrenal gland
synthesis occurs in vesicular compartments
what is needed to convert norepinephrine to epinephrine?
SAM
ascorbate plays a role in hormone activation via
alpha-amidation
alpha-amidation is essential in __ activation
alpha-amidation is essential in hormone activation
hormone activation: ascorbate provides electrons in __ dependent mechanism
hormone activation: ascorbate provides electrons in cytochrome b-561 dependent mechanism
vitamin c reduces several oxygen-centered __ and __
vitamin c reduces several oxygen-centered radicals and reactive species
vit C is an antioxidant due to the __ power of __
vit C is an antioxidant due to the reducing power of ascorbate
antioxidant function of ascorbate (3 things work together)
glutathione + Vit C + Vit E
assessment of vit C, best method
WBC content of vit C
assessment of vitamin C problems
no functional measure other than scurvy
vitamin C deficiency and symptoms
scurvy
4 Hs
hemorrhage
hyperkeratosis
hypochondriasis
hematologic abnormalities
earliest manifestations of scurvy are
dermatologic
some early signs of scurvy are
unspecific
decreased appetite, fatigure, weakness
groups at risk
malnourished ppl:
1. cancer cachexia
2. low SES
3. drug and alcohol
4. elderly men
5. children
6. keto diet (no fresh fruits or veggies)
3 vitamin c controversial treatments (aka it does not work as a treatment)
CVD
cancer
common cold