Transcript What are Vitamins?

TUMS
Azin Nowrouzi, PhD
1
History
 Dumas (1871) individuals fed on pure minerals, water,





proteins, fats and carbohydrates did not maintain good
health.
Lunin (1880) similar finding in animals, milk restored
them to normal
Eijkman (1897) Beri-beri occurred in those fed on
polished rice. Rice-polishings cured them. ..toxin in
polished rice and antitoxin in rice polishings!
Grijns (1901) tried to isolate toxin but did not find any.
There may be a protective substance in rice polishing.
Pokelharing, McCollum, Hopkins (1911)
Corroborated the findings of Lunin. The protective
substance present in milk were named “accessory factors”
by Hopkins.
Funk (1911-1912) isolated crystalline substance from
rice polishings that could cure polyneuritis in pigeons.
2
Origin of the word VITAMIN
Casimir Funk, a Polish biochemist, isolated an antiberberi substance from rice polishing.
 Named it vitamine
 An amine
 Vital for life
Originally, it was thought these necessary compounds
were all amines. Since they were vital to our health they
became known as
“vital amines”, ie. vitamines.
When it was discovered that some were not amines, i.e.,
not ' --ines', the name was changed to:
vitamins
3
4
What are Vitamins?





Vitamins are micronutrients:
Nutritionally important organic compounds
Required in very small amounts.
Cannot be synthesized by the human body.
Do not enter into tissue structures unlike proteins.
Do not undergo degradation for providing energy unlike
carbohydrates and lipids.
Plants and animals synthesize vitamins.
– Vitamins form through biochemical life processes of the plants
and animals we eat.
Examples:
1. Most mammals can synthesize vitamin C; not humans and primates.
2. No mammal can synthesize B vitamins but rumen bacteria do.
3. Some function as vitamins after undergoing a chemical change:
Provitamins (e.g., β-carotene to vitamin A).
5
Coenzymes, Cofactors, and
Prosthetic groups
Vitamins bind the enzyme either loosely or
tightly:
 Coenzymes are lost upon dialysis because
they bind the enzyme loosely.
 When they bind enzymes tightly, they are
considered prosthetic group.
 The term cofactor includes such compounds
but also includes other molecules such as
metal ions that may be necessary for enzyme
activity.
6
Classification
Fat - soluble vitamins are much more
soluble in fats, hydrocarbons and similar
solvents than in water
 Vitamins A, D, K, E
Water- soluble vitamins are much more
soluble in water than in “organic solvents”.
 C, B complex
7
Classification, Requirements, Absorption
Water-soluble
Name(Letter)
RDA
(mg)
Thiamin (B1)
Riboflavin (B2)
Niacin (B3)
1.5
1.7
2
Pantothenic acid (B5)
Pyridoxine (B6)
Biotin (B7)
Folic acid (B9)
10
2
0.3
0.4
Cobalamin (B12)
Ascorbic acid (C)
6 g
60
Absorption: at the small
intestine.
Transported away from
small intestine in blood.
Typically not stored;
instead, kidney filters
excess into urine except
vitamin B6 and B12
 Thus, important to get
these vitamins daily.
 Toxicities almost unheard
of.
8
Classification, Requirements, Absorption
Oil-soluble
Name (Letter)
RDI
Retinol (A)
5000 IU
Calciferol (D)
400 IU
Tocopherol (E)
30 IU
Phylloquinone (K)
70 g
Absorption: Along with dietary fat in small intestine.
40-90% absorption efficiency.
Transported away from small intestine in
chylomicra via blood and lymph (depending on
size).
9
B Complex Vitamins
Vitamin Chemical name
B1
B2
B3
B4
B5
B6
B7
B8
B9
B10
B11
B12
Thiamine
Riboflavin
Nicotinamide (niacin)
Adenine (no longer considered a vitamin)
Pantothenic acid
Pyridoxine
Biotin
Inositol
Folacin (folic acid)
p-aminobenzoic acid (PABA) / H1
L-carnitine / b-hydroxy-g-trimethylammonium butyrate
Cyanocobalamin
10
B Complex - General features
1.
Present in all plant and animal cells.
2.
Generally act as components of coenzymes in
metabolism of carbohydrates, lipids and proteins,
especially in energy-yielding reactions.

Dietary requirement is closely linked to metabolic rate.
3.
Absorbed by passive diffusion (except B12) in small
intestine and any excess is excreted in urine i.e. there
is little or no tissue storage (except B12, some folic
acid).
4.
Must be continually supplied in diet (or by ruminal
synthesis).
11
Vitamin B1 - Thiamine
• Present in tissues as thiamin pyrophosphate (TPP)
• TPP is an essential coenzyme for oxidative decarboxylation of alphaketo acids
– pyruvate to acetyl CoA
• Deficiency
– beriberi in humans
– polyneuritis in birds
– bracken fern poisoning in ruminants and horses
• antithiamin activity
Thiamine, or thiamin,
sometimes called aneurin
chemical formula C12H17N4OS
12
Functions
1. Transketolase reactions of the
Pentose phosphate pathway
(hexose monophosphate shunt).
TTP (thiamine triphosphate)
is required for nerve function
(unrelated to coenzyme
activity).
1. Oxidative decarboxylation
of pyruvic acid.
2. Oxidative decarboxylation
of –ketoglutaric acid.
13
14
E1 uses TPP to release CO2 and produce
HydroxyethylTPP (HETPP)
15
Thiamine Deficiency (B1) Beriberi
Dry beriberi –
peripheral
neuropathy, atrophy
Wet beriberi – dilated
cardiomyopathy
Due to peripheral
dilation of arterioles
16
Alcohol, Wernicke Korsakoff syndrome:
Alcohol dilated
cardiomyopathy
Ataxia (inability to coordinate muscular movements
due to nervous disorders).
Confusion.
Memory loss/confabulation (to fill in gaps in memory by
fabrication).
Opthalmoplegia – can’t follow light source.
Nystagmus-involuntary jerking of the eye.
17
Vitamin B2 or G = Riboflavin
• Essential constituent of
flavoproteins (e.g., FAD)
• Hydrogen carrier in
glycolysis, TCA and
oxidative
phosphorylation
• Deficiency
– curled toe paralysis in
birds
18
Deficiency symptoms
1.
Inappetence, poor growth,
vomiting, skin eruptions and
eye abnormalities in pigs.
•
•
•
•
Cheilosis/Angular stomatitis
(fissure at the angle of the
mouth)
Localized seborrheic dermatitis
of the face
Vascular changes in the cornea
Purple smooth tongue due to
loss of tongue papillae
(Glossitis).
Cheilosis/Angular stomatitis
2. Poor growth and "curled toe
paralysis" in chicks.
•
The toes frequently curl inward
and they may be unable to
stand.
Glossitis
19
Chemical structure
• Isoalloxazine ring system = dimethylbenzene + pteryn
• Ribitol (Reduced ribose) attached to N10
Riboflavin
20
FMN
FAD
5
1
5
1
riboflavin 5’-phosphate
Flavokinase
(riboflavin kinase)
FAD
FMN + ATP
FAD + ppi
synthetase
21
22
Chemical structure and atom numbering of
the flavin mononucleotide
23
Riboflavin Functions
• Essential constituent of the
– Flavoproteins
– Flavin mononucleotide (FMN)
– Flavin adenine dinucleotide (FAD)
• These play key roles in hydrogen transfer
reactions associated with
– Glycolysis
– TCA cycle
– Oxidative phosphorylation.
24
Dietary Sources
• Dairy products
• organ meats (liver and heart) but not
muscle meat.
• Green leafy plants (especially alfalfa)
• Yeast and animal products
• Cereals are poor sources so poultry fed
cereal-based rations should receive
supplemental riboflavin.
25
Niacin = Vitamin B3
• Amide derivative of nicotinic acid
– Can be synthesized from trytophan
• Essential constituent of NAD and NADP
• Hydrogen carrier catalyzed by dehydrogenase enzymes
– ATP synthesis
• Deficiency
– Pellagra in farm animals and humans
• Fiery inflammation of tongue, mouth and upper esophagus
Nicotinic acid
Nicotinamide
26
NAD+
NADP+
Functions:
Active coenzymes:
nicotinamide-adenine
dinucleotide (NAD+)
nicotinamide-adenine
dinucleotide
phosphate (NADP+).
Both are extremely
important in
hydrogen transfer
reactions catalyzed
by dehydrogenase
enzymes.
ATP synthesis, from
oxidation of primary
fuels (glucose, fatty
acids and to a lesser
extent, amino acids)
(NAD+)
Also important in
reductive
biosynthesis
(NADP+)
27
28
29
Deficiency symptoms
1. Pellagra in farm animals and humans (fiery inflammation of tongue, mouth and upper
esophagus).
2. Poor growth, enteritis and dermatitis.
3. Occurs in people who subsist mainly on corn which is low in both niacin and
tryptophan
4. The signs of pellagra include dermatitis, diarrhea, dementia (the three Ds) and loss of
tongue papillae.
Sources of B3
Most non-corn-based diets contain adequate amounts of nicotinamide or its
precursor, tryptophan.
30
Vitamin B4- Adenine
• Adenine is no longer considered a vitamin !
• purine (pyrimidine + imidazole)
•
•
•
•
•
•
FAD
NAD
NADP
CoA
S-AdoMet
PAPS (Phosphoadenosine
phosphosulfate)
• ATP
31
Energy charge (EC) within cells
The energy charge can have a value ranging from 0 (all AMP) to 1(all ATP).
Most cells maintain EC at a constant value with very little variation: The energy
charge of most cells range from 0.8 to 0.95. As EC drops catabolic, energy
producing pathways, such as Glycolysis increase in rate, while anabolic, energy
consuming pathways decrease in rate. The opposite occurs as EC increases,
resulting in a tight control around an optimal value, as seen in the figure. It is evident
that control of these pathways has evolved to maintain the energy charge within
rather narrow limits. In other words, the energy charge like the pH of a cell is
32
buffered.
vitamin B5 / pantothenic acid
•
•
Dipeptide derivative of B-alanine and a butyric acid derivative
Essential constituent of coenzyme A
–
•
Acyl transfer
Coenzyme A is essential for the formation of energy as adenosine triphosphate (ATP)
from carbohydrate, protein, alcohol, and fat. Coenzyme A is also important in the
synthesis of fatty acids, cholesterol, steroids, and the neurotransmitter
acetylcholine, which is essential for transmission of nerve impulses to muscles.
33
Coenzyme A and Acetyl coenzyme A
• Essential constituent of coenzyme A, Pantothenic acid combines with
ATP and cysteine in the liver to generate CoA-SH.
• CoA-SH transfers activated acyl groups, R-(C=O)-, such as acetyl
group by binding them as a thioester. Acyl transfer is important in the
TCA cycle and de novo fatty acid synthesis.
34
Vitamin B5 deficiency
• Deficiency symptoms
• 1. Poor growth, diarrhea, loss of hair,
characteristic "goose-stepping" in pigs.
• 2. Poor growth and feather development,
dermatitis in chickens.
• In humans: headache, fatigue, impaired
muscle coordination, abdominal cramps,
and vomiting
• Sources
• Widely distributed in plants (especially
legumes and cereal) and animal products.
35
Lipoic Acid &
DiHydroLipoic Acid (DHLA)
lipoic acid = Internal disulfur of 6,8-dithiooctanoic acid.
Lipoic Acid (LA) is part of a redox pair.
oxidized form
reduced form
36
Structure
PDH = Pyruvate
dehydrogenase
complex
37
Lipoic acid
• Alpha Lipoic acid is a natural substance
found in certain foods and also produced
in the human body.
• Alpha Lipoic acid is a disulfide
compound found naturally in
mitochondria as the coenzyme for
pyruvate dehydrogenase and ketoglutarate dehydrogenase.
38
The coenzyme function for pyruvate dehydrogenase
and -ketoglutarate dehydrogenase
39
• Clinical Uses for R Alpha Lipoic Acid
– Perhaps the best use of R-alpha lipoic acid is as a life extension
nutrient. It acts as:
•
•
•
•
•
an anti-oxidant
anti-glycation agent
blood sugar normalizer
mitochondria activator
glutathione enhancer.
• Dosage of R Alpha Lipoic Acid
– As a nutritional supplement, doses of 50 to 100 mg per day are
generally recommended.
– As a Therapeutic agent, higher doses may be used.
– In Germany, dosages of 600 mg per day are prescribed for
preventing the damaging effects of hyperglycemia in diabetes.
– Larger doses, 1200 mg given intravenously, have been used to treat
aminita mushroom poisoning.
• R Alpha Lipoic Acid Side Effects and Precautions
– Clinical research has shown no evidence of carcinogenic effects
with administration of alpha lipoic acid. Serious side effects have not
been observed, even at high doses. Minor side effects include skin
reactions and gastrointestinal effects, such as nausea and vomiting.
40
Pyruvate dehydrogenase complex (PDH)
The reaction is:
Pyruvate + NAD+ +CoASH
PDH
Acetyl CoA + NADH + H+ + CO2
5 non-protein molecules
(coenzymes) required for this
enzyme catalyzed reaction are:
NAD+ and CoASH (coenzyme
A); (these are present in the
equilibrated reaction formula,
as can be seen above)
TPP (thiamine pyrophosphate),
Lipoic acid and FAD (flavin
adenine dinucleotide)
participate in the reaction but
do not show up in the
equilibrated reaction formula.
E1 = Pyruvate dehydrogenase
E2 = Dihydrolipoamide acyltransferase
E3 = Dihydrolipoamide dehydrogenase
41
Mechanism of the reaction catalyzed by
PDH complex
42
E2 uses lipoic acid to transfer the
hydroxyethyl group from TPP to CoASH in
order to produce AcetylCoA
43
44
Definition of terms
• MDR = Minimal Daily Requirement
– The minimal oral intake necessary to prevent the
symptoms and signs of vitamin deficiency from
appearing.
• RDA = Recommended Daily Allowance
– An estimate of the adequate vitamin intake in each
age group.
• Vitamin levels in foods or supplements are
sometimes stated in Retinol Equivalents (REs)
or in International Units (IUs).
– for Retinol: 3 IU = 1 RE = 1µg (= 6µg carotene)
– 10µg calciferol = 400 IU vit.D
45
46