VITAMINS and COENZYMES

INGRID ITANOV 2010/2011

Introduction to Vitamins
VITAL + AMINES = VITAMIN Organic molecules, essential for the normal growth and development, required in tiny amounts Cannot be synthesized by mammalian cells must be supplied in the diet Vitamin C human Vitamin A - from precursor Vitamin K, H gut flora Vitamin D skin (UV light)

FUNCTIONS

Regulate metabolism, help convert lipids and saccharides into energy Hormones (vitamin D) Antioxidants (vitamin E) Regulators of cell and tissue growth and differentiation (vitamin A) Precursors for enzyme coenzymes (B-complex)

AVITAMINOSIS - chronic or long-term vitamin deficiency (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 ANTIVITAMINS a substance that destroys or inhibits the metabolic action of a vitamin.

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

Antivitamins - chemotherapy of several infectious diseases Classification: 1. Enzymes decomposing vitamins (tiaminase, ascorbase) 2. Compounds forming nonactive complexes with vitamins (avidin) 3. Compounds structurally similar to vitamins (sulphonamides)
O
H2N C OH O

H2N
Sulphonamide

S NH2 O

Paraaminobenzoic acid (PABA)

Sulphonamides prevent bacterial multiplication, without toxicity to the human tissues

GTP

PABA

Sulphonamide prevents growth and division of MO

interfering with PABA action

FOLIC ACID

COENZYME (THF)

Purin and pyrimidin synthesis

PABA growth factor for MO H2N SO2 H2N COOH

sulphonamide

p-aminobenzoic acid (PABA)

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 K Quinons Vitamin F Vitamin A - Retinol Vitamin D - Calciferol Vitamin E - Tocoferol

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

VITAMIN A = R E T I N O L
Its provitamin - -carotene - (red, orange pigments in plants and fruits) - Antioxidant Structure: tetraterpenoid containing -ionone ring with an unsaturated side chain -, - a - provitamin A

15 15'

O2

-carotene karotn
Fe2+
dioxygenase dioxygenza

CHO

COOH

all-trans retinal dehydrogenase dehydrogenza

11 1

isomerase izomerza

kyselina retinov Retinoic acid

CH2OH
1

11

trans retinol1 - vitamn A1 Premeny -karotnu a vitamnu A1

11-cis retinal

CHO

All-trans-retinal

11-cis-retinal

Retinol

Kyselina Retinoic retinov 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. Excess bone loss, hip fracture (increase of osteoclasts cells, that break down bones) Reproduction sperm production, menstrual period Resistance to infectious disease deficiency leads to increased frequency and severity of disease Epithelial cell "integrity they require vitamin A for proper differentiation and maintenance. Lack of vitamin A - the skin becomes keratinized and scaly, and mucus secretion is suppressed.

VISION CYCLE
R

LIGHT
E

RHODOPSIN (PIGMENT)

T CIS-RETINAL I NERVE IMPULS

RETINAL ISOMERASE

OPSIN

TRANS-RETINAL-OPSIN

N TRANS-RETINAL NADH+H+
DEHYDROGENASE

NAD+ TRANS -RETINOL

Retinolesters (liver) transport by blood proteins

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

-carotene supplements (high doses) Lung cancer / smokers / Skin discoloration Retinal Birth defects Liver problems Reduced bone mineral density that may result in osteoporosis Coarse bone growths Hair loss Excessive skin dryness/peeling Death Signs of acute toxicity nausea, vomiting, headache, dizziness, blurred vision, loss of muscular coordination

SOURCES
-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

Increases Ca into bloodstream by promoting absorption of

Calcium and Phosphorus from food in the intestines and reabsorption of Ca in the kidneys, enabling normal mineralization of bone 2 types: D2 derived from precursor ergosterol present in plants D3 derived from precursor 7-dehydrocholesterol present in skin

Structure similar to steroid hormones (cortizol, estradiol, progesteron) - derived from cholesterol

UV 7-dehydrocholesterol (skin) (provitamin) cholecalciferol (D3, calciol)

UV Ergosterol (plants) (provitamin) ergocalciferol (D2, ercalciol)

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 sunscreen

7-dehydrocholesterol
Plants

Cholekalciferol (D3)

Ergosterol

pre-D2

UV

Kidneys: 25-hydroxylase Liver: 1-hydroxylase

SKIN
7-dehydrocholesterol

Increased parathyroid hormone

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) body characteristics (skin color and body fat)

DEFICIENCY

Leads to impaired bone mineralization, and to bone softening diseases including:

RICKETS - a childhood disease - impeded growth, and deformity of the long bones OSTEOMALACIA - a bone-thinning disorder occurs exclusively in adults proximal muscle OSTEOPOROSIS - reduced bone mineral density and increased bone fragility

Stunted growth

Large forehead

Odd curve to spine or back

Odd-shaped ribs and breast bones Wide joints at elbow and wrist

Large abdomen

Wide bones

Odd-shaped legs

Wide ankles

Vitamin D malnutrition may also be linked to an increased susceptibility to several chronic diseases: high blood pressure tuberculosis cancer periodontal disease multiple sclerosis chronic pain memory loss autoimmune diseases including type 1 diabetes

Sources of vitamin D
Fatty

Fish liver oils Fatty fish species A whole egg Beef liver, cooked UV-irradiated mushrooms (Vitamin D2)

Vitamin E Tocopherols antisterile vitamin

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 protects cell membrane lipids from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction

Free radical

Cell

Mitochondria

vitamn E R vitamn E vitamn E RH

O=C O-C HO-C vitamn E O radikl L-ascorbic kys eliny L-ascorbic acid acid radical Las korbovej

Radical of

+ vitam n C

H-C HO-C-H CH 2OH

O=C O-C O HO-C H-C HO-C-H

O=C O-C O HO-C

O=C HO-C O HO-C H-C HO-C-H

2 ascorbate

O=C O=C O O=C

H-C HO-C-H

H-C HO-C-H
2 dehydroascorbate

Radical of radikl L-ascorbic L-ascorbic kys eliny Lacid radical acid

CH 2OH

radikl L-ascorbic kys eliny L-ascorbic Lacid radical acid as korbovej

Radical of

CH 2OH

CH -OH glutatin- t Glutathione reduk tz a reductase

CH -OH

as korbt Ascorbic acid

dehydroaskorb Dehydroascorbic acid

GS-SG

2 GSH

Nonenzymatic scavenging of free radicals by vitamins

Nonenzyme scavenging of freeradiklov radicals by vitamins Neenzmov vychytvanie vitam nmi

NADPH

Pentose pentzafos ftov Phosphate cyklus cycle

NADP+

STRUCTURE: tocol, forms 8 basic derivatives -tocopherol is a most effective form

R3 R2 HO R1
Chromanol ring HO- group - reduction of free radicals Saturated side chain penetration in membranes
R3

CH3
R1 Tocol -CH3 -CH3 -H -H

CH3
R2 -CH3 -H -CH3 -H

CH3
R3 -CH3 -CH3 -CH3 -CH3

CH3

R2

CH3

CH3

CH 3

CH3 CH3

HO
R1

tocotrienol

Deficiency neurological problems, anemia Natural Sources green leafy vegetable, vegetable oils, nuts, seeds, spinach, broccoli, soybean oil

VITAMIN K - QUINONES

Vitamin K1 (phylloquinone) - from plants sources Vitamin K2 (menaquinone) - made by intestinal bacteria (production can be disturbed by antibiotics, Crohn disease, gallstones) Vitamin K3 (menadione, menadiol) - synthetic

German koagulation

vitamin K

Overview Promotes normal blood clotting (coagulation) Bone metabolism Vascular health Biochemistry coenzyme for a vitamin K-dependent carboxylase carboxylation of glutamic acid gammacarboxyglutamic acid (Gla) involved in binding Ca2+
Vitamin K

clotting factor-glutamic acid nonactive

carboxylase

clot.factor-Gla-Ca2+ active

CO2

Bone metabolism gamma-carboxylation of osteocalcin (bone-related protein) in the presence of vitamin K Vascular health decreases calcification in the arteries by absorbing the hardened calcium to lessen risk of heart disease

Deficiency
Rare in healthy adults: 1) vitamin K widespread in foods 2) vitamin K cycle conserves vitamin K 3) large intestine bacteria synthesize vit. K 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

(K2)

Isoprene units

Toxicity

Vitamin K1, K2 no known toxicity Vitamin K3 interferes with glutathione (antioxidant) oxidative damage to cell membranes. - injections liver toxicity, jaundice, hemolytic anemia in infants

Warfarin Bromadiolon (anticoagulant) (Anticoagulant)

Natural Sources

green leafy vegetables alpha-alpha, Brussel sprouts, spinach, kale, cabbage, avocado, cheddar cheese

VITAMIN F ESSENTIAL UNSATURATED HIGHER CARBOXYLIC ACIDS Structure: unsaturated higher carboxylic acids

Linoleic acid - 2 double bonds 18:2 Linolenic acid - 3 double bonds 18:3 Arachidonic acid??? 4 double bonds 20:4 synthesized from linoleic acid in the body

Fatty acids needed for: normal growth, behavior, healthy cell membranes, well balanced hormone level, immune system

Linoleic acid -6 fatty acid

Arachidonic acid -6 fatty acid

Linolenic acid -3 fatty acid

ARACHIDONIC ACID WITH 4 DOUBLE BONDS

cyclooxygenase

lipoxygenase

epoxides prostaglandins prostacyclins cytochrom P450 tromboxanes leukotriens

The eicosanoids from AA generally promote inflammation

VITAMIN B1 THIAMINE, ANEURINE (antineuritic factor, antiberiberi factor)

PYRIMIDINE and THIAZOL rings linked through methylene bridge Antagonists Sulfites (food preservatives) attack at the methylene bridge

VITAMIN B1 THIAMINE, ANEURIN

Natural thiamine phosphate derivatives:

thiamine monophosphate (TMP) thiamine diphosphate (TDP) (pyrophosphate TPP) thiamine triphosphate (TTP)

Phosphate derivatives involved in many cellular processes

COENZYME = thiamine diphosphate cocarboxylase in catabolism of saccharides and aminoacids

Thiamine pyrophosphate TPP - cofactor for the pyruvate dehydrogenase - alpha-ketoglutarate dehydrogenase catalyzed reactions - the transketolase catalyzed reactions of the pentose phosphate pathway.

TPP

TPP

Deficiency
severely reduced capacity of cells to generate energy BERI-BERI - affecting the peripheral nervous system (polyneuritis) and/or the cardiovascular system, with fatal outcome

Overdose
Hypersensitive reactions resembling anaphylactic shock

Natural Sources
Meat, potatoes, bananas, lentils, beans, yeast

Interactions
Antibiotics - Decrease thiamine level

Overview Essential to energy generation Riboflavin - precursor for the coenzymes FAD, FMN redox reactions FLAVIN MONONUCLEOTIDE (FMN) FLAVIN ADENINE DINUCLEOTIDE (FAD) The enzymes requiring FMN or FAD as cofactors flavoproteins involved in redox reactions (succinate dehydrogenase and xanthine oxidase)

VITAMIN B2 RIBOFLAVIN
Lactoflavin, ovoflavin, vitamin G

ribitol
Riboflavin powder.

Riboflavin solution

METHYL DERIVATE OF IZOALOXAZINE + RIBITOL

FUNCTION:

Key role in energy metabolism - required for the metabolism of lipids, saccharides, and proteins

It is the central component of the cofactors FAD (flavinadenin dinucleotide) and FMN (flavinmononucleotide)

Riboflavin Flavinmononucleotide (FMN)

Flavinadenine dinucleotide reduc. (FADH2)

FAD
Nitrogens 1 & 5 transfer hydrogen in FADH2

Riboflavin

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

Food sources
Food
Fortified cereal Milk (nonfat) Egg (cooked) Almonds Spinach (boiled) Salmon (cooked) Cheddar cheese Chicken, dark meat (roasted) Beef (cooked) Broccoli (boiled) Asparagus (boiled) Halibut (broiled)

Serving
1 cup 1 cup (8 ounces) 1 large 1 ounce 1/2 cup 3 ounces* 1 ounce 3 ounces 3 ounces 1/2 cup chopped 6 spears 3 ounces

Riboflavin (mg)
0.59 to 2.27 0.34 0.27 0.23 0.21 0.12 0.11 0.16 0.16 0.10 0.13 0.08

Vitamin B-3, Niacin, vitamin PP

Nicotinic Acid

Nicotinamide

nicotinic acid + vitamin

Niacin is not a true vitamin in the strictest definition since it can be derived from tryptophan.

Nicotinamide adenine dinucleotide (NAD+) and Nicotinadenine dinucleotide phosphate (NADP+) - cofactors for numerous dehydrogenases (lactate and malate dehydrogenases)- acceptor Hduring alcohol oxidation

NADH

-OH phosphorylated in NADPated in NADP+ (ATP, ATPase)

NICOTINAMIDE ADENINE DINUCLEOTIDE (NAD+)

alcohol to be oxidized

Alcohol dehydrogenase
Transfer: H-

NADH

H+
Aldehyde Residue NAD+ Residue NAD+

Riboflavin unit

Coenzyme Residue+

Reoxidation of NADH

Coenzyme Residue+

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, brewers 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

D-pantoate

-alanine

Pantothenic Acid

Fatty acids

Fatty acids

Krebs cycle

Respiratory chain

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. Toxicity Mild intestinal distress and diarrhea at worst

Pyridoxine (Pyridoxol )

Pyridoxal

Pyridoxamine
All three compounds are efficiently converted to the biologically active form of vitamin B6, PYRIDOXAL PHOSPHATE (PDP)

Pyridoxal Phosphate (PDP)

Overview

Affects the bodys 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 help against mental depression A role in preventing heart disease prevents homocysteine build up (damage to blood vessel linings)

Folic acid

hyperhomocysteinemia cause of atherosclerosis

Homocystein

Cystein

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

VITAMIN H - BIOTIN

FUNCTION Cofactor of enzymes that are involved in CARBOXYLATION reactions (e.g. acetylCoA carboxylase, pyruvate carboxylase) helps to transfer carbon dioxide CO2 Key role in the metabolism of lipids, proteins and carbohydrates 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 arising from its interaction with nuclear histone proteins

DEFICIENCY

hair loss, depression, halucination, muscle pain, dermatitis

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 Long-term use of anti-seizure medications Raw eggs - avidin from egg whites + biotin = complex preventing absorption of biotin deficiency
SOURCES gut flora, liver, egg yolk, nuts, seeds, soya

vit. H

imidazol

valeric acid

thiophane

STRUCTURE - imidazol and thiophane heterocyclic ring with valeric acid

COENZYME - BIOCYTIN
Biotin + Lysin-enzyme = Biocytin (biotinyllysin)
ATP CO2

carboxybiocytin

Coenzyme of carboxylases enzymes transporting CO2

Biotin

Biocytin

Carboxybiocytin

HN

Biotin

Carboxybiotin

Activation of CO2 by biotin - formation of carboxybiotin

Vitamin B9 - Folic Acid

:

Overview Nucleotide biosynthesis DNA and RNA synthesis and repair Cofactor in biological reactions involving folate Important during periods of rapid cell division and growth Production of red blood cells, prevention of anemia. 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

pterin

PABA

Glutamic acid

Folic Acid
positions 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 PABA (para-aminobenzoic acid)- vitamin character not synthetized in the organism

Folic acid
Metotrexate Aminopterin
(competitive inhibitors)

Dihydrofolate reductase

THF

DNA Synthesis

GTP

PABA

Sulphonamide prevents growth and division of MO

interfering with PABA action

FOLIC ACID

COENZYME (THF)

Purin and pyrimidin synthesis

PABA growth factor for MO H2N SO2 H2N COOH

sulphonamide

p-aminobenzoic acid (PABA)

Deficiency Neural tube defects in developing embryos Megaloblastic anaemia, mood disorders and gastrointestinal disorders Overdose Prostate cancer latin word folium = leaf Interactions Methotrexate - Folic acid efficacy reduced Natural Sources Green leafy vegetables, yeasts, animal liver

Spina bifida

malformation of the spine

VITAMIN B12 - Cyanocobalamin

Function Synthesis of DNA and erythrocytes Coenzyme during conversion of methylmalonyl to succinyl CoA Coenzyme during conversion of homocystein to methionine Functioning of brain and nervous system Benefits Promotes growth and cell development Natural Sources Dairy products, Eggs

Deficiency Nausea, loss of appetite, sore mouth Deficiencies - rare The liver can store up to six years worth of vitamin B12 Pernicious anaemia develops as a result of a lack of intrinsic factor in the stomach leading to malabsorption of the vitamin. Interactions Tobacco/Alcohol - Reduces the absorption of vitamin B12

Cyanocobalamin

B12 Synthesis (MO)

B12 - protein
hydrolysis

B12

protein
Intrinsic faktor (IF) (stomach)

B12-IF

Absorption (small intestine)

Transcobalamine II

B12-transcobalamine II (circulation)

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

Overview Participates in oxidation-reduction reactions

Ascorbic acid

Dehydroascorbic acid

Enzyme block

Gulonic acid

L-ascorbic acid

L-dehydroascorbic acid

The vast majority of animals and plants are able to synthesize their own ascorbic acid (excluding humans, guinea pigs, bats)

FUNCTION
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

vitamn E R vitamn E vitamn E RH

O=C O-C HO-C vitamn E O radikl kys eliny L-ascorbic Lacid radical as korbovej

+ vitam n C

H-C HO-C-H CH 2OH

O=C O-C O HO-C H-C HO-C-H CH 2OH radikl kys eliny L-ascorbic Lacid radical

O=C O-C O HO-C

O=C HO-C O HO-C H-C HO-C-H CH 2-OH as korbt ascorbate

O=C O=C O O=C

H-C HO-C-H CH 2OH radikl kys eliny L-ascorbic Lacid radical as korbovej

H-C HO-C-H CH 2-OH

dehydroaskorb dehydroascorbate glutatin- t Glutathione reduk tz a

reductase

GS-SG

2 GSH

NADPH

Nonenzyme scavenging of freeradiklov radicals by vitamins Neenzmov vychytvanie vitam nmi

Pentose pentzafos ftov Phosphate cyklus cycle

NADP+

Deficiency Muscle weakness, swollen gums, loss of teeth, tiredness Scurvy - avitaminosis Liver spots on the skin Spongy gums

SCURVY

Overdose Flushed face, headache, increased urination, lower abdominal cramps Natural Sources Fruits and vegetables

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

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. Colour of flavonoids from yellow to dark violet

Flavonoids

Pigments for flower coloration producing yellow or red/blue pigmentation They also protect plants from attacks by microbes and insects They show anti-allergic, anti-inflammatory, anti-microbial and anticancer activity. The beneficial effects of fruit, vegetables, and tea or even red wine have been attributed to flavonoid compounds rather than to known nutrients and vitamins

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

LIPOIC ACID

Coenzyme aerobic decarboxylation and transacylation during photosynthesis Growth factor of several bacteria and protozoa

Antioxidant dihydrolipoic acid regenerates glutathione, vitamin C and E - acts in hydrophilic and lipophilic environment

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 administration - mushroom poisoning, heavy metal intoxication

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

UBIQUINONE COENZYME Q
Present in the respiratory chain of mitochondria and in membranes of various organels (ER, peroxisomes, lysosomes) It is not a vitamin - all animals, including humans, can synthesize ubiquinones Fat soluble Transports electrones Antioxidant due to its ability to transport electrones Important for energy production in cells

Coenzyme Q3

CH2=C(CH3)CH=CH2
isoprene (2-methyl-1,3-butadiene )

mitochondria

Vonkajia membrna

Semiradical Oxidized form

Reduced form

Biosynthesis
1) Synthesis of the benzoquinone structure from either tyrosine or phenylalanine 2) Synthesis of the isoprene side chain from acetylcoenzyme A (CoA) via the mevalonate pathway 3) The joining or condensation of these two structures

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

adenine

ribose

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 is made from adenosine diphosphate (ADP) or adenosine monophosphate (AMP) and its use in metabolism converts it back into these precursors

 ATP - substrate in signal transduction pathways by KINASES - phosphorylate proteins and lipids ADENYLATE CYCLASE - uses ATP to produce the second messenger molecule cyclic AMP cAMP

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+

Adenylate cyclase

ATP

cAMP