Vitamins

František Duška

Nomenclature

• Definition: compound indispensable for metabolism (usually co-enzyme), which cannot be synthetized in the body

• Nomenclature:– is historical and therefore confusing

– according to order of discovery

– a letter covers whole group of compounds

Vitamins:

• Water soluble: – indispensible for the intermediary

metabolism

– anemia preventing

– vitamin C

• Lipid soluble: A, D, E, K

Lipid-Soluble Vitamins

• Resorption from the gut is coupled with the absorption of fat

• Fat malabsorption (e.g. pancreatic insuficiency, xenical) can lead to vitamin deficiency

• Hypervitaminosis is possible due to poor water-solubility and slow renal excretion

Water-Soluble Vitamins

• Deficiencies can occure relatively quickly (except B12)

• Readily exreted by the kidney when surpassing the renal threshold - toxicity is rare

Vitamin A - Retinol

-caroten: yellow and green vegetable

cleavage (6mg to 1mg)

Retinol/-al/-ic acid: liver, yolk, milk

Vitamin A - Functions

• Both -caroten and retinol are antioxidants

• Retinol-P as a glycosyl donor for the synthesis of glycoproteins and proteoglycans

• Steroid-hormone-like action• Vision

Vitamin A - Deficiency and Toxicity

• Deficiency:– hyperkeratosis due to impaired epithelial

regeneration and mucus sercetion

– imunity disturbancies and anemia

– night-blindness

• Toxicity: !!! teratogenic!!!– “polar-bear liver eaters“, otherwise

uncommon

Vitamin D

• Is rather a hormone than a vitamin: can be synthetized in the body from 7-dehydrocholesterol (UV light is recquired)

Cholecalciferol - saltwater fish, liver, egg

(liver)

25-hydroxycholecalciferol

(kidney - PTH)

1,25-dihydroxycholecalciferol = calcitriol

Vitamin D - Action

• Increase calcium absorbtion (calbinden expression in the enterocyte)

• Promotes bone resorbtion (with PTH)• Inhibits Ca excretion by the kidney

Vitamin D - Deficiency and Toxicity

• Deficiency:– fat malabsorption, vegans, the eldery, renal

failure (impaired 25-hydroxylation)

– rickets in children and osteomalacia in adults (soft bones due to impaierd mineralization of normal organic matrix)

• Toxicity:– hypercalcemia with hypercalciuria (!stones),

bone demineralization

Vitamin E

• a mixture of tocopherols• Function:

– antioxidant: O. scavenger

– possible role in the respiratory chain or heme synthesis

– helps to prevent atherosclerosis

• Deficiency and toxicity: unknown

Tocopherol

Vitamin K

• A group of quinone derivates:– K1(phytylmetaquinone) from green veg.

– K2(multiprenylmenaquinone) syntethized by the intestinal bacteria

• Function:– recquired for the synthesis of clotting factors II.,

VII, IX and X.

– indispensable for osteocalcin synthesis (= Ca-binding protein of the bone matrix)

František Duška:

carboxylation of Glu residues to gama-carboxyglutamic acid form a chelat-like comp., indispensable for Ca binding

František Duška:

carboxylation of Glu residues to gama-carboxyglutamic acid form a chelat-like comp., indispensable for Ca binding

Vitamin K

Vitamin K (cont.)

• Deficiency:– increase coagulation time (Quick test),

i.e. increase the risk of hemorhage and decrease th risk of thrombosis

– newborns or long-term antibiotic treatment, fat malabsorbtion

• Vitamin K antagonists (Warfarine) are widely used as an anticoagulant drug.

Water-Soluble Vitamins

It’s useful to learn features common for whole group of

vitamins!

Water-Soluble Vitamins

1. For energy metabolism:– B1, B2, B6 and niacin

– pantothenic acid and biotine

2. Hematopoetic vitamins:– Folic acid and B12

3. Vitamin C

“Energy-Releasing Vitamins“

• Are turned to co-enzymes of key reactions of energy metabolism

• Sources: whole-grain cereals, meat, yolk, yeasts

• For B1, B2 and B6 is recommended daily dose 1 to 2 mg for the normal adult.

“Energy-Releasing Vitamins“

• Deficiencies can appear in alcoholics– otherwise rare: extreme diets, the eldery,

increased recquirements (pregnancy…)

• Symptoms are derived from impaired energy metabolism:– rapidly growing tissues (cheilitis, dermatitis,

diarhoea)– peripheral and central nervous system– malaise

Vitamin B1 (Thiamine)

• is a precursor for TDP: co-enzyme of:– PDH and KG-DH (Krebs cycle)– transketolase (pentose-P pathway)– ? possible role in nerve transmission

• Recomended daily dose is dependent oncarbohydrate and alcohol intake

• Sources: whole-grain cereals (incl. flour), yeast etc.

Thiamine deficiency

• In whom?– alcoholics

– polished rice as a major source of energy

• Beri-beri: impairment of nervous tissue, heart failure, muscle weakness

Vitamin B2 Riboflavine

• As a part of FMN and FAD• Important for respiratory chain and

various red-ox reactions• Deficiency in alcoholics, impairment of

the skin and mucous membranes

Niacin = Nicotinic Acid

• a part of NADH & NADPH molecules in the form of nicotinamid

• can be synthetized from tryptophan• Deficiency = pelagra = 3Ds:

– dermatitis

– diarhoea

– dementia

Vitamin B6 (Pyridoxin)

• Pyridoxin, pyridoxal, pyridoxamin are all turned to pyridoxalphosphate (PLP)

• Recquired for:– transamination

– other reactions (e.g. serotonin and catecholamine synthesis, -ALA synthesis, homocystein breakdown)

• Deficiency causes neurologic symtoms

Panthotenic Acid Biotin

• Panthotenic acid is a part of CoA– used by more than 70 enzymes

– widespread in all food, deficiency not described

• Biotin is a co-enzyme of carboxylation– pyruvatecarboxylase: anaplerotic for

Krebs cycle and gluconeogenesis

– AcCoA carboxylase: FA syntesis

“Hematopoetic vitamins“

The lack of B12 and/or folate causes macrocytic anemia.

“Hematopoetic vitamins”

• Both co-operate in one-carbon metabolism, recquired for:– purines and dTMP (i.e. nucleic acids)– conversion of homocystein to Met– other: choline, Ser, Gly

• Deficiency leads to:– macrocytic anemia (impaired DNA synthesis)– hyperhomocysteinemia (risk factor of

atherosclerosis)

Folic Acid• Absorbed and stored as polyglutamate

reductase

dihydroholate (FH2)

reductase

tetrahydrofolate (FH4)

= active form

Vitamin B12

• Cyanocobalamin