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Vitamins Hormones Aquaculture - a new industry. History of Vitamins. Life is a series of Chemical Reactions taking place in cells in different tissues. This leads to the questions: What chemicals (foods) are required ? How can these be distributed ?
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Vitamins • Hormones • Aquaculture - a new industry
History of Vitamins Life is a series of Chemical Reactions taking place in cells in different tissues. This leads to the questions: What chemicals (foods) are required ? How can these be distributed ? Essential Nutrients for Human Health Carbohydrate, Fat, Protein, Vitamins, Minerals and Water • Vitamins - enzyme cofactors • Essential Amino Acids - body tissues etc • Essential Fatty Acids - cell membranes etc • Mineral Ions - many individual functions • Hormones - Communication between different parts of the body .
The development of the concept of vitamins Scurvy - known for hundreds of years . Disease involves:- - rapid exhaustion - muscular pains - gums ulcerate & teeth drop out - lung and kidney troubles - eventual death 1497-98 Vasco da Gama Lisbon/Africa/India • 160 crew of which 100 died of scurvy On long sea voyages sailors lived on- Biscuits & salted beef (no vitamin C) In 1577 Spanish Galleon found adrift - everyone on board was dead The development of the idea that vitamin C prevented and cured scurvy took a long time and many hopeful pointers were ignored
The route to a cure for scurvy • 1536 French explorer Jaques Cartier - discovered the St Lawrence River - sailed to Quebec - spent winter - 25 died of scurvy BUT:- - a local Indian told them to drink tea made from needles & bark of tree Treatment worked - but no one took much note. [Now we know that these leaves have vit C] • 1747 James Lind - Doctor, British Navy - expts: oranges, lemons and scurvy Excellent results BUT................ Further expts with boiled juices failed. • 1795 British Navy - lime juice in rations British referred to as Limeys
Captain James Cook - many long voyages 1728-1779 O Rations of lime juice & sauerkraut (Vit C) O Encouraged eating of fresh fruit at ports O No deaths from scurvy O Gave him advantage over rivals ! It was now clear that there was a Diet - Disease - relationship but no real concept of details. • In particular, the crew of the Endeavor were to be guinea pigs in the Navy's fight against "the scourge of the sea"--scurvy. The human body can store only about 6 week's worth of vitamin C, and when it runs out seamen experience lassitude, rotted gums, hemorrhaging. Some 18th century ships lost half their crew to scurvy. Cook carried a variety of experimental foods onboard, feeding his crew such things as sauerkraut and malt wort. Anyone who refused the fare would be whipped. Indeed, Cook flogged one in five of his crew, about average in those days. .
1800 Another major disease Beri-beri - Asia, South America & Pacific Islands - Symptoms of Beri-beri o Nervous disorders (persecution complex) o Paralysis in legs (+oedema) o Paralysis in lungs & heart death 100 years ago young fit sailors died by the hundreds - on duty in Dutch East Indies .Dreadful death through inability to breath • 1886 Dutch doctor - Eijkman investigated Beri-beri for 3 years but no progress. Then he noticed:
O Lab chickens fed luxury rice (for soldiers) died gradually with beri-beri-like symptoms O When the ill chickens were fed common (unpolished) rice, they recovered O Expts repeated sucessfully with 300,000 prisoners in Dutch East Indies O 1907 Eijkman isolated extract of bran - containing a special nutrient needed for health Eijkman Put Mice on : Prot, Fat & Carb only High death rate versus Prot, Fat & Carb + milk or +egg yolk All OK --Identified the compound as thiamin: present in whole-grain products, brown rice, meat products
, 1905-12 Hopkins (England); Similar, extended expts with rats • 1911 Funk (Poland) Said - 4 substances in food prevented 4 diseases - beri-beri, scurvy, pellagra and rickets: - Thought they were amines and vital for life Vital Amine = Vitamine Later - not all are amines - hence VITAMIN Identified later as: • Beri-Beri: Vit B1 (Thiamin) • Rickets: Vit.D • Scurvy: Vit. C • Pellagra: Vit. B3 (niacin, nicotinic acid)
Vitamin C • 1928 Szent-Gyorgyi (Poland) isolated pure vit C • 1933 Haworth & Hirst - structure of vit C • 1935 Vitamin C sold in shops • 1950 Linus Pauling & Common Cold ?? • 1995 Are vitamins C and E important in cancer prevention ??
Vitamin C (Ascorbic Acid) Required byNot required by - Humans All other - Guinea Pigs Animals - Most Fish Glucose Vitamin C In humans the last stage in this conversion is missing Biochemical Role of Vit C Hydroxy Proline Proline Collagen Amino acid residues in protein Enzyme + Vitamin C In the absence of vitamin C collagen is not properly formed. This leads to Scurvy.
Role of Thiamine and Other Vitamins The concept of enzyme cofactors • FOR SELF STUDY • Various molecular functions of vitamins and cofactors • http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.section.1088
Vitamins • The functional role of coenzymes is to act as transporters of chemical groups from one reactant to another. The chemical groups carried can be as simple as the hydride ion (H+ + 2e-) carried by NAD • Many coenzymes are water-soluble derivatives of vitamins. • The main clinical symptoms of dietary vitamin insufficiency generally arise from the malfunction of enzymes, which lack sufficient cofactors derived from vitamins to function • The most prominent function of vitamins is that they act as cofactors for enzymatic reactions. • Vitamins generally cannot be synthesised by mammalian cells and, therefore, must be supplied in the diet. The vitamins are of two distinct types: Water soluble and oil soluble
Enzyme cofactors • Many enzymes require the presence of an additional, non-protein, cofactor • metal ions such as Zn2+, Cu2+, Mn2+, K+, and Na+. • Some cofactors are small organic molecules called coenzymes. The B vitamins • thiamine (B1) • riboflavin (B2) • niacin (nicotinic acid) (B3) are precursors of coenzymes. • Niacin is a precursor of Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) which are two of the most important coenzymes in the cell
Co-Factors • A coenzyme acts along with an enzyme and will be regenerated later. • A coenzyme is a separate molecule from the enzyme protein. CH3CH2OH + NAD+alcoholdehydrogenaseCH3CHO + NADH + H+ Regenerated by other reactions Nicotinamide adenine dinucleotide (NAD+) is derived from the vitamin niacin. A prosthetic group acts in a similar fashion but it is firmly attached to the enzyme. CH2.CO2H Enzyme CH.CO2H Enzyme CH2.CO2H + FAD CH.CO2H + FAD2H Metal Ions - can also be essential factors or certain enzymes. Enzyme Glucose Mg++ Glucose-6-phosphate ATP ADP 71
Biochemical Role of Thiamine Glucose Glycolysis Lactic Acid Pyruvic Oxidative Decarboxylation Acetyl Co-A Acid Kreb’s Cycle Thiamine pyrophosphate is a cofactor in the 1st reaction linking glycolysis & Kreb’s Cycle Linked to use of O2 Lack of thiamine build up of lactic & pyruvic acids N.B. Oxidative processes occur in the mitochondria 75
The roles of NAD+ and NADP+NAD+ is co-factor in catabolic redox reactions; NADP+ is a cofactor in anabolic redox reactions; They accept and donate electrons and protons NADPH The dehydrogenases remove hydrogen and electrons from the substrate and transfer it to the coenzymes NADP and NAD. As these electrons are passed to an electron acceptor (or hydrogen acceptor), energy is released. The cell is able to store this energy as chemical energy (usually in the form of ATP).