Water soluble Vitamins & C (mine)

Vitamins are...

organic compounds w/ regulatory functions (essential in diet)

organic means what

it contains carbon (ex: water (H2O) is not organic)

vitamins and energy yielding

yield no energy

Preservation of vitamins (what are they sensitive to)

exposure to light, heat, air, water & alkaline

**water can cause vitamins to leach out of food

Fat soluble vitamins are generally...

stored (except K)

Water soluble vitamins are generally...

excreted (except B12 & B6)

Deficiency occurs when...

lacking in diet & stores are depleted

according to Juma, deficiency occurs when and suboptimal occurs when?

deficiency: storage depletion in body

suboptimal: lack of intake from diet

How to preserve?

eat ASAP, the sooner the less chance of nutrient loss

if absorption is defective... what will likely occur

Deficiency is likely

ex: fat malabsorption, alcohol abuse, intestinal disease (CF, Crohn's, Celiac)

EAR:

RDA:

AI:

UL:

what do they stand for and what are they

List Fat soluble vitamins

A, D, E, K

List water soluble vitamins

B complex:

- Folate

- B12

- B6

- thiamin

- riboflavin

- niacin

- biotin

- pantothenic

vitamin C

vitamin C is a... (function)

antioxidant & enzyme substrate

Forms of vitamin C

Reduced: Ascorbic acid/ascorbate

Oxidized: dehydroascorbic acid

Vitamin C is synthesized by ____ except _____

synthesized by most animals, except some primates, birds, humans

why can we not synthesize vitC

absence of gluconolactone oxidase

(glucose—> L-gulonolactone—> needed enzyme—> L-ascorbate)

reduced form (what does this mean)

gains -e

is more negative

oxidized form (what does this mean)

loses -e

becomes more +

reducing agent does what/ what happens to it

the reducing agent will lose electrons

the molecule being reduced gains electron

oxidizing agent does what/ what happens to it

the oxidizing agent will gain electrons

the molecule being oxidized loses electrons

D-glucose pathway/vitaC synthesis pathway

- starts w/ glucose

- halts after l-glulonolactone bc we lack enzyme

-then becomes another molecule that spontaneously becomes L-ascorbate (C)

- enzyme: gulonolactone oxidase

how is vitamin C commonly found in food (in what form)

mostly as reduced (ascorbate)

Vit C is destroyed by what? stable when?

- destroyed by heat, light, oxidation, alkaline

- stable in acid conditions

what can push vitas to brink of destruction?

metallic minerals (Fe, Cu) cause oxidative destruction yielding diketogulonic acid

Ascorbic acid digestion...

- not required

ascorbic acid absorption

• uses what carriers

- absorption by SVCT1 (main carrier) & SVCT2 (meta active tissue)

what are SVCT carriers dependent on?

sodium! (SVCT= sodium dependent vit C transporter)

what is the difference between SVCT1 and SVCT2?

• SVCT2 active in metabolically active tissue while SVCT1 in mostly active in the gut (main carrier)

how is absorption related to intake

decreases with intake

ex: if take a huge supplement it wont do any good, it will just be excreted and barely any will be absorbed

what may occur to ascorbate prior to absorption

may be oxidized (into dehydroascorbate)

transport of ascorbic acid in blood (how is it transported?)

in free form

storage of ascorbic acid

- tissues concentration is > plasma

Dehydroascorbic acid found in...

food or oxidized in GI

dehydroascorbic acid absorption occurs how

- via GLUT 1 & 3

how may vit C be absorbed if oxidized before absorption and intake is high (what transport may it use)?

absorbed by passive transport if intake is high

what occurs to dehydroascorbate once it is absorbed

it is reduced back into ascorbate by dehydroascorbate reductase (glutathione dependent)

how is vit C absorbed mostly (in what form; by what transport system)

as ascorbate in specific energy dependent transport system

(SVCT’s are Na dependent which usually indicates energy)

how is dehydroascorbate reduced to ascorbate (and what cells do this)

- Intestinal cells

- under action of dehydroascorbate reductase (glutathione is critical but NADPH & dithiol glutaredoxin can be used instead)

what other molecules can be used by dehycroscarbotate reductase instead of glutathione?

NADPH and dithiol glutaredoxin

Rate of absorption of vit C

16-98% based on needs

avg from 70-100mg is 70-90%

- falls rapidly w/ supplement use

uptake into tissues of vit C via what

SVCT1 and SVCT2

Difference in SVCT 1 & 2

2 is MUCH more metabolically involved

Tissue Levels of Vitamin C

exceed plasma by x3-10 fold

Blood Levels of Vitamin C

Plasma & RBC 70%; WBC 30%

WBC is x80 fold higher than plasma

Vitamin C storage (how long, major tissues, major organ, max body pool)

- quickly excreted, no major long term storage

- major tissue sites: pituitary & adrenal glands

- major organ sites: liver, spleen, kidneys, pancreas & heart

- max body pool of 2g

Ascorbic acid function's & mechanisms (6) — know because it then leads to those roles

-Antioxidant

-Cosubstrate

-Collagen synthesis

-Carnitine synthesis

- Tyrosine catabolism

- Neurotransmitter synthesis

What role does vitamin C play in collagen synthesis?

Vitamin C is involved in 3 hydroxylation reactions

What amino acids are precursors for collagen synthesis?

Proline and lysine.

What are the key enzymes involved in collagen synthesis?

Prolyl hydroxylase (4- & 3-) and lysyl hydroxylase.

What is the cofactor required for collagen synthesis?

Iron (Fe) is the cofactor, which is reduced by ascorbate.

What does ascorbate convert iron into during collagen synthesis? What is ascorbate converted to?

Fe3 + —> Fe2+

Ascorbate —> dehydroascorbate

What is the precursor for carnitine synthesis?

Lysine

What methylates lysine in carnitine synthesis?

S-adenosyl methionine (SAM)

What role does Vitamin C play in the reduction of iron? (in carnitine synthesis)

It acts as a reducing agent, converting Fe3+ to Fe2+.

What is the first step in the conversion of trimethyllysine to 3-hydroxytrimethyllysine?

It is catalyzed by trimethyllysine dioxygenase/hydroxylase.

What is the last step in carnitine synthesis involving ascorbate?

Ascorbate acts on the enzyme 4-butyrobetaine dioxygenase to produce carnitine.

ascorbates role in carnitine synthesis (explain what occurs)

step 1: trimethyllysine is converted into 3-hydroxytrimethyllysine by trimethyl-lysine hydroxylase. For this to occur ascorbate reduces iron (Fe3+ —> Fe2+) and is oxidized into dehydroascorbate

last step: 4-butryobetaine is converted into carnitine by 4-byturobetaine hydroxylase. For this to occur ascorbate reduces iron (Fe3+ —> Fe2+) and is oxidized into dehydroascorbate

What amino acid is required for tyrosine synthesis?

Phenylalanine

What enzyme facilitates the synthesis of tyrosine from phenylalanine?

Phenylalanine monooxygenase (which is iron dependent)

In which organs does tyrosine synthesis occur?

Liver and kidneys

what must be regenerated in the process; what does this

tetrahydrobiopterin must be regenerated

vit C does regenerates it

What is the role of Vitamin C in the regeneration of tetrahydrobiopterin?

it reduces it

Explain how Vitamin C can regenerate cosubstrate

can help tetrahydrobiopterin become dihydrobiopterin then back to tetrahydrobiopterin

What else Vitamin C reduce in the catabolism process?

Copper (Cu)

What role does vitamin C play in tyrosine catabolism?

Vitamin C is a reducing agent for Fe.

What is the first step in the conversion of p-hydroxyphenylpyruvate in tyrosine catabolism?

It is converted to homogentisate.

**ascorbate reduces Fe for this to occur

What does vitamin C convert homogentisate into?

4-maleylacetoacetate via homogentisate dioxygenase.

What condition is caused by a defect in the dioxygenase enzyme?

Alkaptonuria.

What is alkaptonuria?

It is the accumulation of homogentisic acid, leading to painful joints and urine oxidation (black).

What is the starting amino acid for the synthesis of DOPA?

Tyrosine

What enzyme converts Tyrosine to DOPA?

Tyrosine monooxygenase

What is the product of the conversion of Tyrosine by tyrosine monooxygenase?

Dihydrophenylalanine (L-Dopa)

What cosubstrate is involved in the formation of L-Dopa?

Tetrahydrobiopterin (which requires NADPH)

What role does ascorbate play in norepinephrine synthesis?

L-dopa is converted into dopamine,

It acts as a factor in dopamine monooxygenase (enzyme) to form norepinephrine because reduces Cu.

precursor for dopamine

L-Dopa

Pathway to make epinephrine & enzyme used

Phenylalanine -> Tyrosine -> Dopamine -> (enzyme: Dopamine monooxygenase) -> Norepinephrine -> (methionine) -> epinephrine

What is the precursor of serotonin?

Tryptophan

enzyme for converting tryptophan —> serotonin

tryptophan monooxgenase

what is the cosubstrate for the reaction

tetrahydrobipterin

How does vitamin C influence tetrahydrobiopterin?

Vitamin C influences the regeneration of tetrahydrobiopterin, which is important in hydroxylation.

What other role does vit C play in this

reduces iron via an enzyme.

What is the role of ascorbate in peptide amidation?

Ascorbate is important for amidation of peptides with C-terminal glycine, forming amidated peptides, hormones, and hormone-like factors.

What is the function of vitamin C in relation to glycine-a-amidating monooxygenase?

Vitamin C acts as a reductant for copper associated with glycine-a-amidating monooxygenase.

Name some hormones and hormone-like factors that are neurotransmitters.

GRP, calcitonin, cholecystokinin, growth hormone, oxytocin, vasopressin, and other releasing hormones.

In which tissues are neurotransmitters and hormones active?

They are active in neuroendocrine tissues such as the brain, thyroid, and adrenal glands.

What is one function of vitamin C related to liver metabolism?

Microsomal metabolism in liver microsomes & reticuloendothelial

What types of compounds can vitamin C act on?

Endogenous & exogenous (xenobiotics)

What role does vitamin C play as an antioxidant?

It reduces via hydrogen or electron donation.

it is a reducer so it will reduce the molecule by giving it electrons***

How does vitamin C exhibit pro-oxidant activity?

It becomes oxidized by reducing iron (Fe) and copper (Cu).

**if it becomes oxidized it, it cant oxidize other things

Under what conditions does vitamin C show pro-oxidative activities?

In vitro & at high concentrations.

Vitamin C as a reducing agent

- reduces transitional metals (Fe & Cu)

- acts on ROS (reactive oxygen species) such as:

hydroxyl, hydroperoxyl, superoxide, alkoxyl, peroxyl

why do we take vitamin C for Colds?

proliferation of macrophages and lymphocytes,

increase killer cells (T cells), destroying histamine

effect of vitamin C on cancer

inhibits nitrosamine formation (via nitrite & nitrate)

strongest effect against oral, esophagus, stomach, colon, lung & breast cancer

effect of vitamin C on CVD

decreases monocyte adhesion

enhances collagen IV (prevents apoptosis)

effect of vitamin C on cataracts & macular degeneration

antioxidant

prevents lipid peroxidation & protein crosslinking

Iron & vitamin C absorption

vitamin C enhances nonheme Fe absorption

metabolism & excretion of vitamin C

Excreted or oxidized to dehydroascorbate—> turned to diketogulonic acid—>

intermediate product are excreted as oxalic, threonic, xylonic acid & xylose (sugar moiety)

Oxalic acid Is & can cause

product of diketogulonic acid & can causes stones

food sources of vitamin c are sensitive too

heat, Fe, Cu & O2