Vitamin C (Ascorbic Acid)
Electrons carry a _____ charge.
negative
. When a neutral molecule accepts an electron, it becomes
negatively charged (reduced).
is carnitine a protein?
no
Scurvy typically manifests when total body Vit C pools below ______ mg and plasma concentrations fall below 0.2 mg/dL. Scurvy can develop within one month with vitamin C intakes less than ____mg/day, but is more likely to occur with an inadequate vit C intake for a duration of at least 4-6 months.
300 mg, 10mg
Primary function:
Antioxidant
Absorption of ascorbic acid... where does it occur & whats required
occurs across the intestinal cell brush border in the small intestine, especially the proximal jejunum, and requires sodium dependent vitamin C transporters (SVCT) 1 and 2.
what is generated In the initial steps of collagen production?
tropocollagen
Ascorbic acid is an electron donor, or reducing agent, and can be converted to DHA by giving up 2 electrons
true
Chronic high doses are purported to be unsafe for people with iron metabolism disorders (hemochromatosis, thassalemia).
true
Free radicals are natural by-products of biochemical reactions in the body.
true
Greater than 2 g/day could lead to adverse GI effects including abdominal pain and osmotic diarrhea (too much water in the bowels).
true
Vitamin C can both donate and accept hydrogen readily which makes it a great antioxidant and reducing agent.
true
Vitamin C does not require digestion prior to being absorbed into the intestinal wall.
true
Vitamin C exists both in the D and L isomer, but it is the L-isomer that exists is biologically active in humans.
true
vitamin C increases non-heme iron absorption
true
Vitamin C function is a cosubstrate in a number of hydroxylation (introduces a hydroxyl group -OH) reactions.
true *Three* hydroxylation reactions requiring vitamin C are necessary for the synthesis of collagen (structural protein found in skin, bones, dentine, connective tissue)
DHA, but not vitamin C, can be absorbed by facilitated diffusion and GLUT1-4 (mainly 1 and 3).
true -DHA is rapidly reduced to Vit C when entering the enterocyte - thereby maintaining a concentration gradient. -Within the enterocyte, DHA is reduced then exits the cell and spreads to the capillaries through the extracellular space.
When molecules of certain substances encounter ROS....
they "quench" the negative charge that causes damage and The ROS become stable molecules. The substances that do the quenching are anti-oxidants.
1) Tyrosine synthesis
• Hydroxylation of phenylalanine to tyrosine requires phenylalanine mono-oxygenase (hydroxylase), Fe+2. O2. tetrahydrobiopterin, NADPH, vitamin C -The hydroxylation reaction that converts amino acid phenylalanine to tyrosine is catalyzed by phenylalanine hydroxylase -A substrate for this reaction is tetrahydrobiopterin, which is converted to dihydrobiopterin. -Vitamin C is needed to regenerate tetrahydrobiopterin from dihydrobiopterin.
Vitamin C role for carnitine
• Required for 2 hydroxylation reaction in synthesis carnitine --> functions as preferred reducing agent, specifically reducing Fe from ferric (Fe3+ ) back to ferrous state (Fe2+ )
Transport and Storage
•Ascorbic acid and DHA are primarily transported in plasma in its free form •Small amounts of DHA are present due to rapid cellular uptake •Cellular uptake occurs via SVCT1. SVCT2 is also present except in skeletal muscle and lungs. •Maximum vitamin C pool is ~2 g.
vitamin C: Potential role as antioxidant in disease
•Colds - vit C supplements (200 mg or more) shortens duration of cold symptoms by 8% in adults and 14% in children ; does not prevent or treat. •Cancer - high intakes of fruit/veg are associated with a decrease risk of some cancers (oral cavity, esophagus, stomach, lung, breast, colon, rectum). •Oral supplementation does not seem to be beneficial; IV at concentrations > 100 times attained from oral ingestion may have some benefit. •Cardiovascular disease - high intakes of fruit/veg are associated with a decrease risk •Eye health - Vit C taken with other specific vitamins may have modest effects in slowing down macular degeneration; no affect on cataracts.
L-tryptophan is an essential amino acid that helps the body
make proteins and certain brain-signaling chemicals.
•Two ways vitamin C is absorbed:
(1) as dehydroascorbic acid, which uses facilitated diffusion and GLUT1-4; and (2) as vitamin C, which has two transporters: sodium ascorbate co-transporter 1 (SVCT1) and sodium ascorbate co-transporter 2 (SVCT2). Vitamin C requires a Na-dependent gradient coupled carrier.
is required for the reduction of DHA. GSH is oxidized to glutathione disulfide (GSSG).
*Glutathione (GSH)
2. the conversion of 4(y)-butyrobetaine to carnitine (catalyzed by 4(y)butyrobetaine dioxygenase
- Last step in carnitine synthesis in the cytoplasm
1. the conversion of trimethyllysine to 3-hydroxy trimethyllysine (catalyzed by trimethyllysine dioxygenase)
- first step in carnitine synthesis in mitochondria
Interactions with other vitamins
-One of vitamin C's most notable interactions is with the mineral iron. -Vitamin C enhances intestinal absorption of nonheme iron most likely by reducing iron ferric state to iron ferrous state. Vitamin C's benefits are thought to be maximized at about 75 mg. It is commonly suggested that individuals, especially if iron deficient, consume vitamin C rich foods such as orange juice when ingesting non-heme iron rich foods to promote iron absorption.
reactive oxygen species (ROS)
-ROS are damaging to cells -They can damage DNA and other structures. --> The damage they cause results in inflammation. -They are sometimes referred to a pro-oxidants or pro-inflammatory molecules
vit C is a Co-substrate for enzyme activity
-Reducing agent in collagen synthesis -Cofactor in Carnitine synthesis -Cofactor in Catecholamine synthesis
SVCT1
-SVCT1 is the main carrier responsible for vitamin C absorption. -SVCT 1 enables absorption of the vitamin in excess of cell needs.
3) Norepinephrine is generated from the hydroxylation of the side chain of dopamine
-The conversion of dopamine to norepinephrine is catalyzed by dopamine beta monooxygenase which contains 8 copper atoms -During the reaction, the cuprous ions (Cu1+) become oxidized to cupric ions (Cu2+). Vitamin C is needed to reduce copper (Cu), at its active site (primarily the adrenal glands), from cupric to cuprous -Norepinephrine is involved in arousal, alertness, vigilance, memory and attention, increases HR, BP, releases glucose from E stores.
During the reaction:
-The hydroxylase incorporates one atom of O2 into the product and the second atom of O2 into the a-ketoglutarate to form the new carboxyl group succinate. -During these reactions, the iron cofactor in the hydroxylase enzymes is oxidized; that is converted from a ferrous to ferric state -Ascorbic acid is required to reduce Fe3+ to Fe2+, forming DHA in the process. -With Fe2+, the enzyme is then able to continue to hydroxylate proline and lysine.
Carnitine synthesis
-carnitine is produced from lysine and methionine -essential for movement of LCFA from cytoplasm into mitochondria for B-ox
vitamin C is a potent reducing agent
-primary water soluble, non-enzymatic antioxidant in plasma and tissues -readily donates to vitamin E and Glutathione
Measures of Nutrient Requirements
1.Recommended Daily Allowance (RDAs) A.Average daily dietary intake level sufficient to meet nutrient requirements of 97% healthy people 2.Dietary Reference Intakes (DRIs) A.Approximations of nutrient needs for the purpose of planning and assessing diets of health people 3.Adequate Intakes (AIs) A.Replaces RDA when there is insufficient data to calculate EARs 4.Estimated Average Requirements (EARs) A.Nutrient requirement for 50% of the healthy people in a specified group/age 5.Tolerable Upper Intake Levels (Uls) A.Highest intake level for a nutrient that is unlikely to cause adverse health
Regular use of Vitamin C (250 mg-1 g daily) reduced the incidence of colds by _______% among some subsets (athletes, soldiers exposed to extreme conditions). Existing evidence has shown Vitamin C modestly and consistently shortens the duration of cold symptoms by about ____% in children and 14% in adults.x
50%, 8%
Over a range of foods, vit C is absorption is about 70-95%.
Absorption decreases with increased intake.
Neurotransmitter synthesis
As with the synthesis of carnitine and collagen, vitamin C reduces mineral cofactors that become oxidized during selected reactions in the synthesis of some neurotransmitters and hormones.
Foods Sources
Characteristics: •Heat labile •Dissolves in water •Destroyed by alkali, oxidation and light. •***Contact with iron and copper destroys Vit C.*** •Stabilized by acidic solutions •Vitamin C can be lost when exposed to air, light and heat.
Ascorbic acid is required to reduce Fe3+ to Fe2+, forming ____________in the process
DHA
With ___________, the enzyme is then able to continue to hydroxylate proline and lysine
Fe2+
Nutrient intake is typically adequate if it meets or exceeds the AI, but may not be adequate if they are less than the AI.
If nutrient intake is more than the RDA and less than the UI, than the intake are likely to be adequate.
Vitamin C as a pro-oxidant:
In the presence of elevated ROS, high doses of Vit C (IV delivery) increases ROS and thereby increases cell apoptosis.
Vitamin C is needed to regenerate tetrahydriobiopterin from dihydrobiopterin.
SEROTONIN SYNETHESIS
when body demands more vit C, what does it demand?
SVCT1
absorbic acid downregulates
SVCT1... this limits absorption when superphysiological doses are ingested
Vitamin C Deficiency
Scurvy •May develop in as little as 1 month •4 Hs of scurvy •Hemorrhagic signs •Hyperkeratosis of hair follicles •Hypochondriasis (psychological manifestation) •Hematologic abnormalities •Treated with 100-500 mg daily until cured
other functions
Tyrosine catabolism Neurotransmitter synthesis - Norepinephrine - Other neurotransmitters and hormones
Is vitamin C an antioxidant?
Vitamin C acts as a reducing agent or electron donor and therefore it is a very effective antioxidant
Collagen Synthesis
Vitamin C acts as a reductant keeping iron in its ferrous state. Vitamin C can reduce iron to the ferrous form --> increases intestinal absorption of nonheme iron. Not clear whether increased consumption of Vitamin C can assist in iron deficiency anemia.
Hydroxylation of Phenylalanine:
Vitamin C is needed to regenerate tetrahydrobiopterin from dihydrobiopterin.
Iron is needed as a cofactor for the hydroxylation of trimethyllysine and 4-butyrobetaine hydroxylase;
Vitamin C is the preferred reductant.
Excessive vitamin C can also interfere with some laboratory tests, including urine analysis.
Vitamin C may act as a reducing agent and thus interfere with tests used for glucose in urine (diabetics) or for blood in the feces (GI tract bleeding).
2) Tyrosine is converted to DOPA
Vitamin C may have a potential role in stress reactions as dopamine is involved in reward, motivation, memory, learning, emotional responses, attention, regulating body movements
Dopamine to norepinephrine:
Vitamin C reduces copper (Cu) at its active site (primarily the adrenal glands) - seems to be needed to allow for release of adrenal hormones into the system.
Vitamin C is transported in blood in the form of free ascorbic acid or dehydroascorbic acid (minor amounts) and is primarily stored in ____________________
adrenal and pituitary glands, eyes, brain, white blood cells.
After these chains are made, vitamin C-dependent hydroxylation reactions occur post translationally and allow __________________ and ______________________
aggregation and further cross linking of the chains
Hydroxylase means that the enzymes add __________________ to the amino acids proline and lysine
alcohol (hydroxyl, -OH)
Nutriture
bodily condition with respect to nutrition and especially with respect to a given nutrient
Antioxidants are substances that can prevent or slow damage to cells caused by
by free radicals, unstable molecules that the body produces as a reaction to the environment and other pressures (stress, disease). --> They do this by giving up some of their own electrons.
Similar to the hydroxylation reactions in collagen synthesis, vit C acts as a reducing agent in _________________ synthesis, reducing iron to its ferrous state (Fe3+) for the reactions catalyzed by trimethyllysine hydroxylase and 4-butyrobetaine hydroxylase.
carnitine
Free radicals are
chemical species of high oxidative potential that can damage the human body on a cellular level.
The enzymes proline hydroxylase and lysyl hydroxylase are important in the formation of the protein ______________
collagen
Antioxidants, are free radical scavengers, which are?
compounds that either reduce the formation of free radicals or react with and neutralize them
In the course of the hydroxylating proline or lysine, ferrous iron (Fe2+) is oxidized to ______________.
ferric iron (Fe3+)
Proline and lysyl hydroxylases require _________________ to function.
ferrous iron (Fe2+)
High doses unsafe for those predisposed to kidney stones, or with certain disorders of iron metabolism. Because Vitamin C metabolism generates oxalix acid, a common constituent of kidney stones
high intakes may increase kidney stone formation. People at high risk should avoid doses > 500 mg/day.
The formation of ___________________________ provides for attachments to CHO moieties and allows for additional post-translational modifications, such as glycosylation and phosphorylation, to further strengthen the collagen.
hydroxylsyl residues
Vitamin C inhibits the renal reabsorption of uric acid...
increasing uric acid excretion acidifying the urine to promote precipitation of uric acid crystals and the formation of uric acid kidney stones.
Carnitine is a non-protein, nitrogen containing compound made from lysine which is critical in fat metabolism, because ....
it is essential to transport long- chain fatty acids from cell cytoplasm into mitochondrial matrix where β-oxidation occurs (thus energy production).
Hydroxylation of the proline to produce hydroxyproline in collagen chains allows for subsequent cross linking via __________________.
lysyl oxidase
Free radicals can cause damage to the parts of the cells such as proteins, DNA and cell membranes by stealing their electrons through ________________. This why free radical damage is also called 'oxidative damage'.
oxidation When there is an imbalance between free radicals and antioxidants in the body (i.e. too many free radicals) it is termed 'oxidative stress'.
The reduction potential of vitamin C is such that it also readily donates electrons/hydrogen ions to regenerate other antioxidants, such as Vitamin E and glutathione, and can help protect LDL from ________________
oxidation, thereby potentially reducing cholesterol level
Visual signs of scurvy:
pale skin, follicular hemorrhaging, red, swollen gums or loose teeth
When a neutral molecule donates an electron, it becomes
positively charged (oxidized).
Vitamin C may also act as a _______________ by reducing transition metals
pro-oxidant -for example cupric ions --> cuprous and ferric ions --> ferrous. -The products from these reactions may cause cell damage by generating reactive oxygen species and free radicals like hydroxyl, superoxide radicals. -Pro-oxidant activity is thought to be minimal but may increase in pathological conditions (toxicity).
Collagen contains a number of hydroxylated _____________ and ____________ that are needed for collagen strands to properly cross-link
prolines and lysines This cross-linking is important for collagen to wind together like a rope, forming the strong triple helix known as *tropocollagen*
Some of these redox reactions produce unstable molecules carrying a negative charge known as
reactive oxygen species (ROS)
Reactions in which electrons are being moved around among molecules are called
redox
Ascorbate is needed to function as a reductant in order to...
reduce iron back to its ferrous (2+) in prolyl and lysyl hydroxylases. Ascorbate acts as a reducing agent to convert the oxidized iron form back to its reduced state in the enzymes lysyl hydroxylase and prolyl hydroxylase --> which incorporate one atom of oxygen in the hydroxyl group of the product and the other in the in succinate.
Vitamin C functions as both an antioxidant and as a cosubstrate for enzyme activity. As a cosubstrate, some enzymes contain a mineral (copper or iron) cofactor and vitamin C functions as a __________________
reducing agent to maintain the iron and copper atoms in the reduced state.
Your body changes L-tryptophan into a brain chemical called
serotonin! Serotonin is a neurotransmitter involved in the transmission of nerve impulses and impacts every part of your body. Helps regulate mood, social behavior, appetite, digestion, sleep, memory, and sexual desire and function. Found primarily in the intestines.
Vitamin C absorption is channeled through
sodium-dependent and gradient coupled carrier mechanism.
Vitamin C as a powerful antioxidant:
superoxide anions, hydrogen peroxide, hydroxyl free radicals.
Ascorbic acid (AH2) acts as a reducing agent in aqueous environments (bloods, ICF) and is efficient in reducing
superoxide, hydroxyl radicals, and hydrogen peroxide
Foods as opposed to supplements are the preferred sources for the intake of vitamins
true -Diets rich in fruits, vegetables, whole grains are associated with reduction in risks for heart disease, type 2 diabetes, metabolic syndrome, and some cancers, among other conditions. -Scientific evidence supports the consumption of foods (fruit, veg, whole grains, meat, fish, poultry, nuts, seeds, legumes) versus the use of supplements to meet nutrient needs and to reduce the risk of diseases.
The type of SVCT transporter depends on the characteristics and requirements in each cell
true -SVCT2 being more frequent in tissues that require a constant supply of ascorbate, even under vitamin C deficiency conditions -SVCT1 is more frequent in cells responsible for tissue distribution of ascorbate
Once oxidized, ascorbic acid needs to be regenerated or reduced to repeat the antioxidant cycle...
true!! -glutathione, thioredoxin -niacin (NADH and NADPH)
vitamin C is derived from glucose
true, but humans are not able to synthesize it because we lack L-gulonolactone Oxidase
Free radicals are atoms or molecules that are highly reactive with other cellular structures because they contain
unpaired electrons
ascorbate, ascorbyl radical, dehydroascorbic acid (DHA)
vit C
•Water soluble vitamin, derived from glucose, its prime function is as an antioxidant. Additional functions include:
•Collagen formation is dependent on vitamin C metabolism. •Vitamin C can reduce iron to the ferrous form, which is more available for intestinal absorption. •It is central in two reactions in the formation of carnitine to allow for longer chain fatty acids to cross the inner membrane of mitochondria for β-oxidation.
Vitamin C -why do we need to consume it?
•Humans are unable to synthesize vitamin C., which is derived from glucose. •Humans lack L-gulonolactone oxidase, the last enzyme in the vitamin C synthetic pathway, to finish the metabolism of glucose. •Vitamin C plays an essential component of: -wound healing -collagen synthesis -antioxidant -->supports regeneration of other antioxidants - which may help with chronic diseases such as cancer, immune function, absorption of nonheme iron.
Vitamin C: Recommended Dietary Allowance
•Men: 90 mg/day •Women: 75 mg/day •Pregnancy: 100 mg/day •Lactation: 120 mg/day •Add 35 mg/day for smokers -Minimum requirement is 75 mg for men and 60 mg for women. -Smoking accelerates the depletion of the body's ascorbic acid pool it is recommended that smokers consume an added 35 mg of vit C daily. For example, 1 orange has 51 mg of Vitamin C. Total body content of Vitamin C is about 300 mg (scurvy) to about 2g.
Vitamin C Toxicity
•UL: 2g/day - nausea, abdominal cramps, osmotic diarrhea, headache, fatigue, and insomnia; hot flashes and rashes; aggravation of gout, urinary track infections, kidney stones; interference of medical tests (false positive or false negative) •High doses: -Osmotic diarrhea -Increased risk of kidney stones •Assessment of nutriture -measure plasma concentration (< 0.2 mg/dL is deficient) or leukocyte concentration (< 10 ug/108 is deficient).
Vitamin C
•Vitamin C is also known as ascorbic acid (AH.2). •At physiological ph, it loses a H and is usually in is ionized form ascorbate (AH-). •Oxidation of ascorbate generates the ascorbyl radical A-, which has one proton and one electron less than ascorbate. •The oxidized form of the vitamin is called dehydroascorbic acid (DHA) and has vitamin activity because it can be converted into ascorbate in body cells.
Water soluble vitamins are handled differently from the way it handles the fat soluble vitamins.
•Water soluble vitamins are absorbed into the portal blood stream and metabolized in the liver. •Fat soluble vitamins enter the lympatic system as part of a chylomicron. • With some exceptions, excess water soluble vitamins are excreted into urine whenever plasma levels exceed renal thresholds; they are not stored in large quantities in the body tissues. •Water soluble vitamins with the exception of Vitamin C, are members of the B complex. •Most of the B complex can be further divided according to their general functions such as energy production and nutrient metabolism, hematopoiesis, and gene expression.