Nomenclature of Enzymes

1. Nomenclature of Enzymes Classes on the basis of reaction type and functional groups.For enzyme classes and subclasses arabic numbers are used. Oxidoreductase NAD(P) acceptor 1.1.1.1 CH-OH donor alkohol-dehydrogenase Main enzyme classes: 1. Oxidoreductase 2. Transferase 3. Hydrolase 4. Lyase 5. Isomerase 6. Ligase

2. Main class: kind of reaction Sub-class: donor group or the type of the reaction Sub-sub-class: acceptor group or substrate Serial number specifies the enzyme itself e.g. 1.2.3.4 means: oxidoreductases aldehyde group donor oxygen acceptor oxalate oxidase Main classes: 1. oxidoreductases 2. transferases 3. hydrolases 4. lyases 5. isomerases 6. ligases

3. 1.) Oxidoreductases 1.X.1.Y: NAD or NADP acceptors = dehydrogenases 1.6.4.Y. NADPH H-donor (and S-S H-acceptor) = reductases 1.3.X.Y.O2 electron acceptor, H2O2 product = oxidases (except cytocrhome-oxidase: H2O) Monooxygenases: 1 atom oxygen built in, another forms water Dioxygenases: both oxygen atoms built in Peroxidases: H2O2 or R-OOH degradation Coenzymes of oxidoreductases may be: NAD, NADP, FAD, FMN, lipoate, ascorbate, DHB, cytochromes, iron-sulfur centres

4. 2.) Transferases 2.1.1. methyltransf. coenzyme: SAM = S-adenosylmethionine (exceptionally betain, methyl-THF) 2.1.2. C-1 units: methyl-, hydroximethyl-, formyl-, formimino-, methylene-, methenyl- coenzyme: THF= tetrahydrofolate 2.2. ketogroup transketolase: TPP, transaldolase 2.3.1. acyltransf. coenzyme: HS-CoA = coenzyme A 2.4. glycosyltransferases:. di-, oligo- and polysaccharide formation (synthases) active forms: UDP-sugar (UDP-glucuronate, PRPP) 2.6.1. aminotransferases: amino acid1 + oxo acid2 = oxo acid1 + amino acid2

5. 2.7. Phosphotransferases = kinases donor: ATP acceptor OH-, COO--, NH2-, HPO42-, etc. 2.8.2. Sulfotr. = sulphate transfer coenzyme: PAPS (phosphoadenosyl-phosphosulfate) 3.) Hydrolases (hydrolysing enzymes) 3.1. esterases carboxyl-, thiol-, phosphate-, sulphate ester hydrolysing 3.2. glycosidases: oligo- és polysaccharide cleaving 3.4. peptidases, proteases = protein degrading 4.) Lyases addition to double bonds or small molecule elimination 4.1. 1.decarboxylases, coenzyme: PLP 4.1.3. oxo acid lyases: citrate-synthase or lyase

6. 4.2.1. Hydrolyases: water elimination or addition: fumarase, enolase, akonitase 4.6.1.1. adenylate-cyclase 5.) Isomerases 5.1. Racemases and epimerases: one group position changed 5.2. cis-trans isomerases 5.3.1. aldo-keto isomerases (aldose-ketose) 5.3.3. double bond position changers (unsaturated fatty acids) 6.) Ligases = synthetases: ATP, CTP, GTP requiring 6.1.1. aminoacyl-tRNA synthetases 6.2.1.acyl-CoA synthetases 6.3.2. peptid synthetases e.g. glutathione = GSH 6.3.5.acid amide producing with Gln donor (GMP, Asn) 6.4. carboxylases, coenzyme: biotin

7. Vitamins: obligatory need for the living organisms for the life - the given creature can not produce, it has to eat • take part in enzyme catalysis, or they are hormons or • other regulating factors. • small organic molecules • B-vitamins: 1,2,3,5,6,7,9,12 and vitamin C are water soluble • A,D,E,K vitamins are lipid soluble • Coenzyme = loosely bound, easily dissotiated from the enzyme, taking part in catalysis, small organic molecule NAD, NADP, CoA • Prosthetic group = strictly bound to enzymes, not dissociated, taking part in catalysis, small organic molecule FAD, FMN, TPP, PLP, THF, DHB, biotin, cobalamine

8. Effect of alcoholism on the metabolism of vitamins 1.) gastroenteritis, diarrhoea → wrong absorption 2.) steatohepatitis, cirrhosis → storing capacity of the liver is decreased especially pyridoxal, folate, cobalamin 3.) competition with acetaldehyde on transport protein → pyridoxin degradation is increased 4.) iron absorbtion increased → iron deposits in liver, ROS formation Coenzymes of energy producing pathways: NAD, FAD, FMN, TPP, CoA, (PLP), biotin Any of them is missing → carbohydrate- lipid-, amino acid degradation is decreased → ATP shortage → fast multiplicating cells (intestine, skin, blood cells) and big energy requireing organs (nervous system, heart, muscles) can not work properly

9. Vitamins taking part in amino acid and nucleotid metabolism pyridoxin, folate, cobalamin In their deficiency the metabolism of amino acids and synthesis of nucleotides, therefore synthesis of nucleic acids (DNA, RNA) is improper mainly in fast replicating cells: blood cells, enterocytes, skin, mucous membranes Excess water soluble vitamins are excreted by kidney, some of them are stored in liver: folate, cobalamin (6 years), pyridoxin (2 month). Even pharmacological doses do not cause poisoning or overdosage, except vit. B3 and B6. Lipid soluble vitamins absorbed and transported together with lipids. Pharmacological doses cause poisoning of vitamin A or D. Vitamin E has many adventageous characteristics, no overdosing

10. Vitamin B1 = tiamin→ TPP= thiamin-pyrophosphate prosthetic group Function: oxidative decarboxylation in enzymes: PDHC, αKGDHC, and transketolase Deficiency: no aerob glucose degradation, citric acid cycle, amino acid degradation leading to ATP-shortage pentosephosphate pathway can not work, NADPH-deficiency Low grade deficiency in elderly and restricted, poor diet: loss of appetite, constipation, depression, peripheral neuropathy, irritability, fatigue Moderate severe deficiency in chronic alcoholists = Wernike-Korsakoff- syndrome: mental confusion, ataxia (missing movement coordination), ophtalmoplegia (lower eye movement capacity) Severe deficiency = beri-beri: in alcoholists, in populations who eat only polished rice: muscle atrophy (disappearance), heart failure

11. Demand increased: carbohydrate rich food, fever, trauma, pregnancy, lactation, tea- and coffee consumers Source: every natural organic food except polished rice, white flour, refined sugar. It is found in the cover of the seeds of cereals.

12. Vitamin B-2 = riboflavin→ FAD, FMN prost. gr. Producers: plants, bacteria Stores: yeast, liver, kidney, egg, milk Function: some dehydrogenases and reductases, all oxidases E.g. succinate deh., mt. glycerol-3-P deh., electrontransport prot. acyl-CoA deh. dihydrolipoyl deh. glutathione red., NADH deh., amino acid oxidases. xanthine oxidase, cytochrome P450 red., pyruvate deh., ketoglutarate deh. Deficiency signs in chronic alcoholists: (inflammations) angular cheilitis (lips), glossitis (tongue), stomatitis (mouth), photophobia, scaly dermatitis

13. Niacin, nicotinic acid, nicotinamide → vitamin B3 NAD, NADP Not really a vitamin, we can synthesize it from tryptophan, but not enough. Synthesis needsTrp, pyridoxin, riboflavin, iron. Sourses: lean meat, oily seeds, legumes, liver, fish (in maize Trp is scarce) Deficiency in starving elderly, alcoholists: pellagra (= rough skin) 4 D symptoms: dermatitis, dementia, depression, diarrhoea and other mucous membranes’ inflammation in GI, and GU tract Function: NAD: dehydrogenases’ characteristic coenzyme NADPH: reductases’ characteristic coenzyme Demand increased: pregnancy, lactation, chronic illness

14. Pantothenic acid = vit. B5 → HS-CoA, ACP Function: acyl-transferases, synthases, synthetases carboxyl-group joins to it by thioesther bond. In carbohydrate, lipid, cholesterol, amino acid metabolism > 70 enzyme Source: every originally living organism, especially liver, meat, milk, egg, legumes, mushrooms, fish, fully ground cereals Sensitive for acids, alkalines and heat Deficiency signs: alone can not occur, just together with other vitamin B types

15. Pyridoxine, pyridoxal, pyridoxamin → pyridoxal phosphate = vit. B6 PLP Function: Glycogen phosphorylase (here the bigest amount) Amino acid metabolism:1. transaminases: Gly,Ala, Val, Leu, Ile, Tyr, Cys, Glu, Asp, ornithine 2. amino acid decarboxylases: noradrenalin, dopamin, adrenalin, serotonin, hisztamin, GABA synthesis 3. hem synthesis (for hemoglobin, myoglobin, cytochromes) 4. sfingolipid synthesis (for membranes) 5. Ser, Thr, Cys, Gly metabolism dehydratases, aldolases, desulfinases, synthases and lyases, cleavage enzyme 6. NAD(P) synthesis

16. Deficiency signs: Irritability, depression, peripheral neuropathy, seizures, microcytic anaemia, glucose intolerance, thrombosis, cardiovascular signs Source: meat, vegetables, fully ground cereals, egg yolk Demand increase: lactation, pregnancy, age, oral contraceptives consumers, protein rich diet

17. Folate = folic acid = vit. B9 → THF = H4F = tetrahydrofolate Function: Ser, Gly, His, Trp, choline degradation Met, dTMP, purin ring synthesis methyl-, methylene, methenyl-, formimino-, formyl-group transfer Source: Every fresh, not heated, originally living food (‘cause heat sensitive)= fresh fruits, vegetables Demand increased: lactation, pregnancy Cause of deficiency: intestinal diseases, certain drugs, improper diet Signs of deficiency: macrocytic anemia, thrombosis, leucocyte number decreased

18. Cobalamin = vit. B12 adenosyl-cobalamin, methyl-cobalamin Function: methyl-THF, methyl-Cbl homocystein methionin L-methylmalonyl-CoA succinyl-CoA Source: exclusively bacteria can synthesize, found in every animal and human cells not found in plants (strict vegetarians are in danger) Deficiency signs: 1.) blood cells pruduction decreased, in fast multiplicating tissues nucleotides, nucleic acids are not produced megaloblastic anaemia, anaemia periniciosa 2.) neurologic signs: acidosis, abnormal myelin sheat formation Deficiency can be: because of hereditary transporter defects, or aquired: gut diseases, anacidity, antibodies

19. Biotin = vitamin B7 biotin Function: Coenzyme of carboxylases : gluconeogenesis/citric acid cycle anaplerotic, lipid synthesis, amino acid degradation Source: nuts, egg, chocolate… Every living organism contains a little, gut bacteria synthesize Deficiency signs: depression, hallucination, dermatitis, muscle pain Cause of deficiency: exteme malabsorption, raw egg white regular consumers

20. Ascorbic acid = vitamin C Ascorbic acid • Function: • in collagen Lys and Pro hydroxilation, collagen stabilization- adrenal gland: adrenalin and corticosteroid synthesis • - nervous system: noradrenalin synthesis • reducing material: Fe3+ (absorption elevated), A- and E-vitamins (antioxidant effect)- folic acid absorption increased • Source: fresh plants (It is degraded during heating or storage). • Deficiency signs: • Scurvy: pinpoint hemorrhages, bruising, osteoporosis (collagen loss) teeth loss, anaemia (iron deficient), wound healing impaired, muscle weakness

21. vitamin K = menaquinone, phylloquinone from animals, from plants Function:in liver gamma-carboxylation of Gln in blood coagulation proteins (necessary for membranebinding during blood coagulation) Deficiency signs: hemophylia Cause of deficiency: lipid malabsorption because of pancreas, bile or intestinal diseases/ dysfunction qumarin overdosage, newborn state(not enough in milk)

22. Vitamin deficiency often occurs in average population: folate, cobalamin, pyridoxin Vitamin deficiency can occur in case of improper diet, alcoholists: thiamin, riboflavin, niacin, ascorbate, phyto/menaquinons Vitamin deficiency occurs only in extreme starvation or severe gut diseases: panthotenic acid, biotin Heat sensitives: folate, ascorbate, thiamin, panthotenate Light sensitive: riboflavin (B2-vit) Absorption complicated, problematic, found only in animals: vit. B-12 Some medicines inhibit their absorption, speed their degradation or antagonists: riboflavin, niacin, pyridoxin, vitamin K, folate Vitamins alone are not enough, the proper enzyme action requires minerals and amino acids (in proper amount and ratio) as well.