VITAMINS and COENZYMES

❖ Organic molecules, essential for the normal

growth and development, required in tiny amounts

Introduction to Vitamins

VITAL + AMINES = VITAMIN

❖ Cannot be synthesized in sufficient quantities by

mammalian cells; must be supplied in the diet

Vitamin C – vitamin for human

Vitamin K, H – synthesized by gut flora

Vitamin A - from precursor beta carotene

FUNCTIONS

• Regulate metabolism, help convert lipids and saccharides

into energy (B-complex)

• Hormones (vitamin D)

• Antioxidants (vitamin E, C)

• Regulators of cell and tissue growth and differentiation

(vitamin A)

• Coenzyme precursors (B-complex)

AVITAMINOSIS - chronic or long-term vitamin lack (beri-beri,

scurvy, rickets and pellagra)

HYPOVITAMINOSIS - any of several diseases caused by

deficiency of one or more vitamins

HYPERVITAMINOSIS – the condition resulting from the

chronic excessive intake of vitamins (vitamin supplements)

side effects – nausea, diarrhea, vomiting

Avitaminoses

▪ Vitamin A deficiency causes xerophthalmia or night blindness

▪ Thiamine (B1) deficiency causes beri-beri

▪ Niacin (B3) deficiency causes pellagra

▪ Vitamin B12 deficiency leads to megaloblastic anemia

▪ Vitamin C deficiency leads to scurvy

▪ Vitamin D deficiency causes rickets

▪ Vitamin K deficiency causes impaired coagulation

▪ Rare in developed world - fortification

ANTIVITAMINS

H2N C

O

OH

Paraaminobenzoic acid (PABA)

H2N S

O

NH2

O

Sulphonamide

Sulphonamides – prevent bacterial multiplication, without toxicity to the human tissues

• substances that destroy or inhibit the metabolic

action of a vitamin

Classification:

1. Enzymes decomposing vitamins (thiaminase, ascorbase)

2. Compounds forming nonactive complexes with vitamins (avidin)

3. Compounds structurally similar to vitamins

(sulphonamides)

Water Soluble Vitamins Fat Soluble Vitamins

Thiamine (B1)

Riboflavin (B2)

Niacin (B3)

Panthotenic acid (B5)

Pyridoxin (B6)

Biotin (B7 ) – vitamin H

Folic acid (B9)

Cobalamin (B12)

Bioflavonoids (P)

Ascorbic acid (vit. C)

Vitamin A - Retinol

Vitamin D - Calciferol

Vitamin E - Tocoferol

Vitamin K – Quinons

Vitamin F

Water soluble vitamins Fat soluble vitamins

Vitamins soluble in water

➢ directly absorbed from intestine into blood

➢ hypervitaminosis – vitamins excreted from the body

Vitamins soluble in fat

➢ require correct function of the liver and gall bladder

➢ hypervitaminosis – toxic effect

Its provitamin - -carotene - (red, orange pigments in plants and fruits)

- Antioxidant

-CAROTENE

VITAMIN A (R E T I N O L)

Structure: tetraterpenoid containing -ionone ring with an unsaturated

side chain

-, - a - provitamin A

α - Carotene

β - Carotene

γ - Carotene

dioxygenáza

CHO COOH

all-trans retinal izomeráza kyselina retinová

dehydrogenáza

CH2OH

trans retinol1 - vitamín A1

Premeny β-karoténu a vitamínu A1

15'

1

1111

1

1

CHO

Fe2+

O2

11-cis retinal

β-karotén

15

-carotene

dioxygenase

Retinoic acidisomerase

dehydrogenase

2

All-trans-retinal 11-cis-retinal

Retinol Kyselina retinováRetinoic acid

Functions of vitamin A

❖ Vision – retinal is a structural part of rhodopsin (visual purple) –

light sensitive pigment in retina

❖ Bone remodeling – function of osteoblasts and osteoclasts

depend on it.

❖ Reproduction – sperm production, menstrual period

❖ Resistance to infectious disease – deficiency leads to

increased frequency and severity of disease

RHODOPSIN

(PIGMENT)

LIGHT

cis-RETINAL trans-RETINAL-OPSIN

NERVE

IMPULS

TRANS-RETINAL

NADH+H+

DEHYDROGENASE

NAD+

TRANS -RETINOL

OPSIN

RETINAL

ISOMERASE

R

E

T

I

N

A

Retinolesters (liver)transport by blood proteins

VISION CYCLE

HYPOVITAMINOSIS A

➢ Night blindness – mild deficiency of vitamin A – inability to

produce sufficient amount of rhodopsin (lack of retinal)

➢ Large deficiency of vit. A – xeroftalmia – keratinisation of the eye

tissue (today in Africa, Asia)

➢ Dry skin, frequent infections, decreased synthesis of thyroid

hormones

HYPERVITAMINOSIS

β-carotene supplements (high doses)

• Skin discoloration

• Lung cancer / smokers /

Retinal

• Birth defects

• Liver problems

• Reduced bone mineral density that may result in osteoporosis

• Hair loss

• Excessive skin dryness/peeling

• Death

Signs of acute toxicity – nausea, vomiting, headache, dizziness, blurred vision, loss

of muscular coordination

SOURCES

The body stores both retinol and beta-carotene in the liver,

drawing on this store whenever more vitamin A is needed

β-carotene - carrot, green leafy vegetables – spinach, kale,

sweet potatoes, yellow and orange fruits

Retinal – liver of polar bear, seal, eggs and fatty fish

VITAMINS D - CALCIFEROL

• maintain normal blood levels of Ca and P by promoting their

absorption from food in the intestines and reabsorption of Ca in the

kidneys, enabling normal mineralization of bones

2 major forms:

D2 – derived from precursor ergosterol present in plants

D3 – derived from precursor 7-dehydrocholesterol present in skin

Structure of provitamins of vitamin D - similar to steroid hormones

- derived from cholesterol

UV

7-dehydrocholesterol (skin) cholecalciferol

(provitamin) (D3, calciol)

UV

Ergosterol (plants) ergocalciferol (D2, ercalciol)

(provitamin)

Adequate amounts of vitamin D3 can be made in the skin after only

10 -15 minutes of sun exposure at least 2x per week to the face,

arms, hands, or back without a sunscreen

UV

Kidneys: 25-hydroxylase

Liver: 1-hydroxylase

Normal vitamin D metabolism

DEFICIENCY

◼ Results from a number of factors:

◼ inadequate intake coupled with inadequate sunlight

exposure

◼ liver or kidney disorders (impair conversion of

vitamin D into active metabolites)

DEFICIENCY

Leads to impaired bone mineralization, and to bone softening

diseases including:

• RICKETS - a childhood disease - impeded growth, and

deformity of the long bones

• OSTEOPOROSIS - reduced bone mineral density and

increased bone fragility

Odd curve to spine or

back

Wide joints at

elbow and

wrist

Odd-shaped

legs

Vitamin D malnutrition may also be linked to an

increased susceptibility to several chronic diseases:

◼ high blood pressure

◼ cancer

◼ periodontal disease

◼ multiple sclerosis

◼ memory loss

◼ autoimmune diseases including type 1 diabetes

Overdose of vitamin D:

◼ Ca release from bones and its deposition in soft tissues

(kidneys, lungs gall bladder, endocrine glands) causing

their calcification

Sources of vitamin D

◼ Fish liver oils

◼ Fatty fish species

◼ A whole egg

◼ Beef liver, cooked

◼ mushrooms (Vitamin D2)

•

Benefits

• Protects lipids (cell membranes), DNA, proteins from

oxidation – ANTIOXIDANT

Protects food fats from going rancid

• Helps to form red blood cells

• Aids in the absorption of vitamin K

Vitamin E – Tocopherols

antisterile vitamin

Free radical

Cell

Mitochondria

Vitamin E protects cell membrane lipids from oxidation by reacting

with lipid radicals produced in the lipid peroxidation chain reaction

O

CH3

CH3 CH3 CH3

R3

R2

HO

R1

O

HO

CH3

CH3

CH3 CH3 CH3

R1 R2 R3

Tocol -CH3 -CH3 -CH3

-CH3 -H -CH3

-H -CH3 -CH3

-H -H -CH3

tocotrienol

STRUCTURE: tocol, forms 8 basic derivativesα-tocopherol is the most effective form

Chromanol ring

HO- group - reduction of free radicals

Saturated side chain – penetration in membranes

R1

R2

R3

Deficiency

neurological problems, anemia

Natural Sources

green leafy vegetable, vegetable

oils, nuts, seeds, spinach, broccoli,

soybean oil

Vitamin K1 (phylloquinone) - from plant sources

Vitamin K2 (menaquinone) - made by intestinal bacteria

(production can be disturbed by antibiotics, Crohn disease)

Vitamin K3 (menadione, menadiol) - synthetic form

German „koagulation“ vitamin K

VITAMIN K - QUINONES

Methylated naftoquinone ring

• Promotes normal blood clotting (coagulation)

• Bone metabolism

• Vascular health

Biochemistry

coenzyme of an enzyme carboxylase –

carboxylation of glutamic acid gamma-

carboxyglutamic acid (Gla) – involved in binding Ca2+

FUNCTIONS

nonactive active

clotting factor-glutamic acid clot.factor-Gla-Ca2+

CO2

Vitamin K

Carboxylase

The vitamin K cycle

Rare in healthy adults: 1) vitamin K widespread in foods

2) vitamin K cycle conserves vitamin K

3) large intestine bacteria synthesize vit. K

Deficiency

Adults at risk:

• those taking vitamin K antagonist - anticoagulant drugs

• adults with significant liver damage

• newborn babies – exclusively breast-fed:

1) vitamin K is not easily transported across the placental

barrier

2) the newborn's intestines are not yet colonized with bacteria

that synthesize menaquinones

3) the vitamin K cycle may not be fully functional in newborns

Natural Sources

green leafy vegetables – alpha-alpha, Brussel sprouts,

spinach, kale, cabbage, avocado, cheddar cheese

VITAMINS SOLUBLE

IN WATER

VITAMIN B1 – THIAMINE, ANEURINE

(antineuritic factor, antiberiberi factor)

PYRIMIDINE and THIAZOL rings linked through themethylene bridge

Antagonists – Sulfites (food preservatives) – attack at the methylene

bridge

- cofactor for several enzymes (pyruvate dehydrogenase,

alpha-ketoglutarate dehydrogenase)

Thiamine diphosphate

COENZYME = thiamine diphosphate

- in the catabolism of saccharides and aminoacids

Deficiency

▪ severely reduced capacity of cells to generate energy

▪ BERI-BERI - neurological symptoms, cardiovascular

abnormalities, and edema with fatal outcome

It affects the nerves to the limbs, producing pain,

paralysis, and swelling

Natural Sources

Meat, potatoes, bananas, lentils, beans, yeast

OverdoseHypersensitive reactions resembling anaphylactic shock

InteractionsAntibiotics - decrease thiamine level

Beri – beri disease

VITAMIN B2 – RIBOFLAVIN

METHYL DERIVATE OF ISOALOXAZINE + RIBITOL

Lactoflavin, ovoflavin, vitamin G

Riboflavin powder.

Riboflavin solution

ribitol

Riboflavin

Flavinadenine dinucleotide

(FAD)

Flavin mononucleotide (FMN)

H-

H+

FADNitrogens 1 & 5 bind hydrogens in FADH2

Deficiency

Fatigue, red, swollen, cracked mouth and tongue, mouth

ulcers, cracks at the corners of the mouth

Riboflavin deficiency is often seen in chronic

alcoholics due to their poor dietetic habits

Overdose

Itching, numbness, a burning sensation

Storage

Riboflavin decomposes when exposed to visible light

This characteristic can lead to riboflavin deficiencies in

newborns treated for hyperbilirubinemia by phototherapy

Vitamin B3, Niacin, vitamin PP

NicotinamideNicotinic Acid

Niacin is not a true vitamin in the strictest definition since it

can be derived from tryptophan.

nicotinic acid + vitamin

!

Nicotinamide adenine dinucleotide (NAD+) and Nicotinamide

adenine dinucleotide phosphate (NADP+) - cofactors for numerous

dehydrogenases (lactate, malate dehydrogenases) - acceptor of

during alcohol oxidation

NICOTINAMIDE ADENINE DINUCLEOTIDE (NAD+)

H-

NADH

-OH phosphorylated in NADPate

!

Reduction of NAD+ to NADH

Function

• Niacin is a precursor to NADH, NAD+ - coenzymes of

oxido-reductases – transfer of hydrogen anion

• Nicotinic acid (but not nicotinamide) - lowers plasma

cholesterol levels (and TAG, LDL, VLDL) and has been

shown to be a useful therapeutic for hypercholesterolemia

• Elevates blood glucose and uric acid production (not

recommended for diabetics or gout)

Deficiency

Dermatitis on the hands and face, weakness

The severe symptoms, depression, dermatitis and

diarrhea - PELLAGRA (3D disease)

Natural Sources

Beef liver, brewer’s yeast, meat, eggs, grains and milk

PELLAGRA

Overdose

Niacin flush, liver damage, stomach ulcers, nausea,

diarrhea, weakness

Overview

• Pantothenate is required for synthesis of coenzyme A –

metabolism of saccharides, proteins, lipids.

• Growth factor for MO

• „Anti-stress vitamin“

Vitamin B5 – Pantothenic Acid

Vitamin B5

COENZYME A

SOURCES

Whole grains - milling removes much of the pantothenic acid

Vegetables – broccoli, avocados

Meats, rice, alfalfa, peanuts, molasses, yeasts

DEFICIENCY

Excessive fatigue, sleep disturbances

Deficiency - extremely rare due to its widespread distribution in whole

grain cereals, meat

Pyridoxine

(Pyridoxol )Pyridoxal Pyridoxamine

Pyridoxal Phosphate

(PDP)

All three compounds are

efficiently converted to the

biologically active form of

vitamin B6, PYRIDOXAL

PHOSPHATE (PDP)

Vitamin B6 – Pyridoxine

!

!

FUNCTIONS

➢ Affects the body’s use of proteins, saccharides

• a coenzyme in all transamination reactions, in some

decarboxylation and

deamination of amino acids

➢ PDP aids in the synthesis of heme

➢ Helps in absorption of vitamin B12 and formation of

erythrocytes

➢ Role in the conversion of tryptophan to serotonin – helps against

mental depression

➢Vitamin B6-magnesium - help attention deficit disorder -

improvements in hyperactivity, and improved school

attention

➢ Vitamin B6 - cure for premenstrual syndrome (PMS)

Deficiency

• Anemia

• Nerve damage (mental confusion, irritability, nervousness)

• Skin problems

• Sores in the mouth

Deficiencies of vitamin B6 are rare

Natural Sources

Potatoes, Salmon, Shrimp, grains,

soya, yeasts, poultry, fish, eggs, nuts

Interactions

Tobacco/alcohol - Reduces vitamin

absorption rates

FUNCTION

• Cofactor of enzymes that are involved in CARBOXYLATION

reactions (e.g. acetylCoA carboxylase, pyruvate carboxylase)

helps to transfer CO2

• Key role in the metabolism of lipids, proteins and saccharides

• It activates protein/amino acid metabolism in the hair roots and

fingernail cells - the “beauty vitamin” - often recommended for

strengthening hair and nails.

• Role in DNA replication and transcription

VITAMIN H - BIOTIN

Carboxybiocytin

BiotinBiocytin

imidazol

valeric acidtiophane

STRUCTURE - imidazol and thiophane heterocyclic ring with valeric acid

DEFICIENCY

• hair loss, hair thinning

• brittle fingernails

• depression, halucination,

• muscle pain,

• dermatitis (skin rash, typically on the face)

Synthetized by intestinal bacteria - deficiencies rare

Deficiency occurs in:

• Alcoholics

• People with inflammatory bowel disease

• Someone who eats large quantities of raw egg whites

• Long-term antibiotic use

Raw eggs -

preventing absorption of biotin

vit. H deficiency

avidin from egg whites + biotin = complex

SOURCES

gut flora, liver, egg yolk, nuts, seeds, soya

:

Functions

• Nucleotide biosynthesis

• DNA and RNA synthesis and repair

• Important during periods of rapid cell division and growth

• Production of red blood cells, prevention of anemia.

• Antioxidant

Vitamin B9 - Folic Acid

Folacin

Benefits

• To carry and transfer various forms of one carbon units

(methyl, methylene, methenyl, formyl or formimino groups)

during biosynthetic reactions (purine nucleotides, dTMP)

• Promotes a healthy pregnancy

Folic Acidpositions 7 & 8 carry hydrogens in dihydrofolate (DHF)

positions 5-8 carry hydrogens in tetrahydrofolate (THF)

• Active form of folic acid - tetrahydrofolate (THF) – coenzyme F –

formylating coenzyme – transfer of 1-carbon moeities

pterin PABA Glutamic acid

• Folic acid is itself not biologically active, but derivative

tetrahydrofolate and other derivatives after folic acid conversion to

dihydrofolic acid in the liver

Deficiency

◼ Neural tube defects in developing embryos

◼ Megaloblastic anaemia,

◼ mood disorders and gastrointestina ldisorders

Overdose

dizziness, headache, anxiety, nausea,vomiting

Natural Sourcesanimal liver and kidneys, sardines, beef, tuna, trout, salmon

Spina bifida

• Malformation of the spine

• Lost ability to control bladder - urination,

• Impaired function of legs

Function• Synthesis of DNA and erythrocytes

• Coenzyme during conversion of methylmalonyl CoA to succinyl

CoA

• Functioning of brain and nervous system

• Antioxidant

• B12 is used to regenerate folate in the body

VITAMIN B12 - Cobalamin

Natural SourcesAnimal liver and kidneys, sardines, beef, tuna, salmon, dairy

products, eggs

Methylcobalamíne Cyanocobalamine 5´-deoxyadenosylcobalmine

DimethylbenzimidazolCorin ring

!

B12 - protein

B12protein

Intrinsic faktor (IF)

(stomach)B12-IF

Absorption (small intestine)

B12-transcobalamine II

(circulation)

Transcobalamine II

B12 Synthesis

(MO) Hydrolysis (stomach)

Binding of B12-transcobalamin II to the cell

receptors

Endocytosis of the complex into cells

Degradation of the complex in lysosomes and liberation

of B12

Coenzyme of enzymes in the cell cytoplasm

Mouth

Salivary glands produce R-protein

Stomach

a. HCl and pepsin release vitamin B-12 bound

to protein in food

b. Free vitamin B-12 binds with R-protein

c. Parietal cells secrete IF (intrinsic factor)

Small intestine

a. Trypsin from pancreas releases R-protein

from vitamin B-12

b. Vitamin B-12 links with IF intrinsic factor

Ileum

Vitamin B-12/ Intrinsic factor complex is

absorbed into blood and binds to transport protein

transcobalamin II

Liver

Vitamin B-12 stored in liver

VITAMIN B-12 absorption

Smallintestine

Ileum

StomachLiver

Salivary gland

Deficiency – develops if the body does not produce enough intrinsic

factor, or if you don’t eat enough vitamin-B12-rich foods

Pernicious anaemia

Nausea, loss of appetite, sore mouth

Deficiencies - rare

The liver can store up to six years worth of vitamin B12

Interactions

Tobacco/Alcohol - Reduces the absorption of vitamin B12

Blood cells of

pernicious anemiaThe cells are larger than

normal and irregular in

shape

Normal blood cellsThe size, shape and color

of these red blood cells

show that they are normal.

Overview

Participates in oxidation-reduction reactions

Ascorbic acid Dehydroascorbic acid

!

Gulonic

acid

L-ascorbic acidL-dehydroascorbic

acid

Enzyme block

➢ The vast majority of vertebrates are able to synthesize their own ascorbic acid

(excluding humans, guinea pigs, bats) from glucose.

✓ Antioxidant (prooxidant)

✓ Cofactor of enzymes used in the synthesis of collagen

✓Tyrosine degradation

✓ Adrenalin synthesis

✓ Carnitin synthesis

✓ Bile acids production

✓ Steroidogenesis

✓ Iron absorption

✓ Metabolism of bone minerals

FUNCTION

SCURVY

Fragility of capillaries

Gums bleeding

Swallen gums

Overdose

Flushed face, headache,

increased urination,

lower abdominal cramps

Natural Sources

Fruits and vegetables

• Pigments for flower coloration producing yellow or red/blue

pigmentation

• They also protect plants from attacks by microbes and insects

VITAMIN P – BIOFLAVONOIDS

❖ • Found in close association with vitamin C - vitamin C .

❖ • Bioflavonoids help maximize the benefits of vitamin C by

inhibiting its breakdown in the body

❖ • Antioxidants, antivirals, and anti-inflammatories

❖ • Protection against infections

❖ • Decrease the cholesterol level

Flavonoids

• Strengthening the walls of the blood vessels (rutin)

❖ • Preventing nosebleeds, miscarriages, postpartum bleeding,

and other types of hemorrhages

❖ • Protection against cancer and heart disease

❖ • Anticoagulant activity (preventing blood clotting)

❖ • Improvement of circulation

❖ • Improvement of liver function

❖ • Improvement of vision and eye diseases

Essencial compounds are rutin, hesperidin, quercetin.

Sources

Citrus fruits, grapes, black current, blackberries, blueberries,

cherries, apricots, cacao, tea

Absorption of the bioflavonoids can be slow, but small amounts

can be stored in the body

LIPOIC ACID

Coenzyme – aerobic decarboxylation and transacylation during

photosynthesis

Growth factor of several bacteria and protozoa

Antioxidant - acts in hydrophilic and lipophilic environment

- dihydrolipoic acid regenerates glutathione, vitamin

C and E

LIPOIC ACID

Chelator

• Lipoic acid – chelates Cu2+, Zn2+ and Pb2+, but not Fe3+.

• Dihydrolipoic acid – chelates Cu2+, Zn2+ a Pb2+ and Fe3+.

- prooxidant – it can reduce Fe3+ to Fe 2+

• Lipoic acid intravenous administration - mushroom poisoning,

heavy metal intoxication

Sources - kidney, heart, liver, spinach, broccoli, peas, potatoes

Brewer´s yeasts

UBIQUINONE – COENZYME Q

• Present in the respiratory chain of mitochondria

• Transports electrones

• Important for energy production in cells

• Antioxidant

• It is not a vitamin - all animals, including humans, can synthesize

ubiquinones

• Fat soluble

Coenzyme Q3

CH3

CH2=C - CH=CH2

isoprene (2-methyl-1,3-butadiene )

Reduced form

Oxidized form

Semiradical

Antioxidant

• Deficiency

Decreased plasma levels of coenzyme Q10 - diabetes,

cancer, and congestive heart failure

• Sources

meat, poultry, fish, nuts,

moderate sources - fruits, vegetables, eggs, and dairy

products

ADENOSINEPHOSPHATES

Adenine

Ribose

Triphosphoric acid

- donors and acceptors of phosphoric acid in all living systems

5´

ribose

adenine

adenosine

Adenosine-5'-triphosphate (ATP)

• Transports chemical energy within cells for metabolism

• It is an energy source produced during photosynthesis and

cellular respiration

• It is consumed by many enzymes in biosynthetic reactions,

motility, and cell division.

• ATP - substrate in signal transduction pathways by

KINASES - phosphorylate proteins

ADENYLATE CYCLASE - uses ATP to produce the second

messenger cyclic AMP

• ATP is also incorporated into nucleic acids

• ATP has several negatively charged groups in neutral solution, it

can chelate metals with very high affinity

• Due to the strength of these interactions, ATP exists in the cell

mostly in a complex with Mg2+

cAMP