* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Enzyme cofactors
Radical (chemistry) wikipedia , lookup
Multi-state modeling of biomolecules wikipedia , lookup
Lactate dehydrogenase wikipedia , lookup
Microbial metabolism wikipedia , lookup
Mitochondrial replacement therapy wikipedia , lookup
Metabolic network modelling wikipedia , lookup
Enzyme inhibitor wikipedia , lookup
Photosynthesis wikipedia , lookup
Adenosine triphosphate wikipedia , lookup
Light-dependent reactions wikipedia , lookup
Biochemistry wikipedia , lookup
Electron transport chain wikipedia , lookup
Amino acid synthesis wikipedia , lookup
Citric acid cycle wikipedia , lookup
Photosynthetic reaction centre wikipedia , lookup
Biosynthesis wikipedia , lookup
Metalloprotein wikipedia , lookup
NADH:ubiquinone oxidoreductase (H+-translocating) wikipedia , lookup
Nicotinamide adenine dinucleotide wikipedia , lookup
Evolution of metal ions in biological systems wikipedia , lookup
Enzyme cofactors T. Kučera (based on an older presentation by J. Novotná) Enzyme cofactors • • • • non-protein, low-molecular enzyme “component” “co-catalyst” required for the activity of the enzyme helper molecules in the enzymatic reaction holoenzyme (active) “consists” of – apoenzyme (the enzyme without the cofactor – inactive) – coenzyme – the cofactor • reaction partner of the substrate • or reactant regenerating the enzyme • cofactors – tightly bound to the enzyme – prosthetic groups • regenerated in the same reaction (isomerases) • or by a reaction with a different substrate – loosely bound – coenzymes • regenerated in reaction with a different enzyme • inorganic – metal ions (Mg2+, Cu+, Mn2+, Zn2+, Fe2/3+, Mo) • organic – heterocycles, often containing phosphate – many contain a nucleotide component – often vitamins or their derivatives • water soluble – B, C, fat soluble – E, K Cofactors by the reaction • of oxidoreductases – NAD, NADP, FAD, FMN, ubiquinone, biopterin, lipoamide, glutathion, FeS-clusters, heme, metal ions • of transferases of 1C-residues – THF, biotin, S-adenosylmethionine • of transferases of other carbon residues – TDP, CoA • of transferases of other groups – ATP, PAPS, UDP, CDP, cobalamin, pyridoxal phosphate Cofactor Vitamin Enzyme reaction (example) Thiamin diphosphate Thiamin, B1 Oxidative decarboxylation FAD, FMN Riboflavin, B2 Redox reactions (transfer of 2H) NAD+, NADP+ Niacin, B3 Redox reactions (transfer of H−) Coenzyme A Pantothenic acid, B5 Metabolism of FA (transfer of acyl) Pyridoxalphosphate Pyridoxin, B6 Transamination, decarboxylation Carboxybiotin Biotin, H, B7 Carboxylation (CO2) Tetrahydrofolate folic acid, B9 Transfer of a 1C-group Ascorbate Vitamin C Hydroxylation reactions (colagen) Menaquinon Vitamin K Transfer of carbonyl group and electrons Lipoamide Lipoic acid Transfer of electrons and acyl groups Cobalamin Cobalamin, B12 Isomerization, methyl transfer NAD (NADP ) + + Redox reaction of NAD • • • • RH2 + NAD+ → NADH + H+ + R (de)hydrogenaion of the C—O or C—N bond proton released to the solution example: lactate dehydrogenase (lactate + NAD+ → → pyruvate + NADH +H+) FAD, FMN Vitamin B2 FMN → ATP-dependent phosphorylation of riboflavine FAD → further reaction with ATP – transfer of AMP to FMN Reduction and reoxidation of FMN and FAD Examples of enzymes with FAD and FMN acyl-CoA dehydrogenase succinate dehydrogenase glycerol-3-phosphate dehydrogenase FAD FAD FAD NADH-reductase (complex I) FMN Coenzyme Q • electron transport chain • human – CoQ10 (Q = quinone head , 10 = number of isoprene units in the hydrophobic chain) Reduced form Oxidized form ATP + P ─ P ─ adenosine (ADP) inorganic phosphate (Pi) + P ─ adenosine (AMP) inorganic pyrophosphate (PPi) • transport of chemical energy within the cell • phosphorylation in signal transduction Pyridoxalphosphate (PLP) • prosthetic group of aminotransferases • cofactor of all transamination reactions and of some decarboxylations and deaminations of amino acids Pyridoxine (vit. B6) Pyridoxal-5-phosphate (PLP) Pyridoxamine-5-phosphate Thiaminpyrophosphate (diphosphate) TPP (TDP) • • • active form of the vitamin B1 (the first discovered vitamin) contains substituted heterocycles pyrimidine and thiazol reactions – reversible cleavage on the C—C bond connecting C=O group with the vicinal reactive group (usually —COOH or —OH) – transfer of 2C-residues in transketolase reactions in the pentosephosphate pathway – oxidative decarboxylation of α-ketoacids and formation of aldehydes (pyruvate → acetaldehyde), cofactor of multienzyme complexes PDH, -KGDH, BCADH Tetrahydrofolate (THF) • Active form of folic acid (vitamin B9) • donor of 1C units of all oxidation levels except CO2 • coenzyme of transferases. N5,N10-THF carries methylene or methenyl • occurs e.g. in the synthesis of nucleotides and nucleic acids Tetrahydrofolate (THF) Coenzyme A • acyl carrier • the thiol reacts with the carboxyl forming a thioester • e.g. transfer of FA from the cytoplasm to the mitochondrion • high-energy compound participating in many metabolic reactions (-oxidation of FA, citric acid cycle, biosynthesis of lipids…) S-adenosylmethionine COOH NH3+ NH3+ CH COOH CH2 CH CH2H CH2 + CH2 ATP + NH2 H3C S C N 2 O H3C S OH OH N N N + HPO42- + H2P2O72- Biotin • cofactor of carboxylation reactions • prosthetic group of acetyl-CoA carboxylase and other ATP-dependent carboxylases • covalently attached to the apoenzyme through the ε‑amino group of lysine Lipoic acid • prosthetic group, transfer of hydrogen and acyl • amidic bond to the ε‑amino group of lysine (lipoamide) • oxidative decarboxylation of ‑ketoacids (PDH, -KGDH, BCADH) Vitamin K • Vitamin K1 (phyloquinone) – plant origin (redox cofactor of phofotosystem I) • Vitamin K2 (menaquinone) – bacterial origin (large intestine, bacterial electron transport chain) • K1 and K2 have different functions Fyloquinone Vitamin K1 Vitamin K2 Menaquinone – K1 – blood clotting – K2 – metabolism of the bones and of the vascular walls, cellular growth Synthetic vit. K derivatives Vitamin K - function • cofactor of hepatic microsomal glutamate carboxylase – formation of carboxyglutamate residues in prothrombin and coagulation factors VII, IX and X (post-translation modification) • carboxylated glutamate chelates Ca2+, enabling the binding of coagulation factors to membranes • forms Ca2+ binding site also e.g. in osteocalcin Tocopherol, vitamin E α-tocopherol quinone formed by oxidation from ‑tokopherol is a cofactor in synthesis of mitochondrial unsaturated FA Chromanol ring | hydrophobic alifatic side chain Vitamin C • hydroxylation of proline and lysine residues (colagen) • synthesis of colagen – prolyl hydroxylase, lysyl hydroxylase and lysyl oxidase contain Fe2+ and ascorbate as cofactors • metabolism of tyrosine in the brain Ions as cofactors Ion Example of an enzyme Cu2+ Cytochrome oxidase, catalase Fe2+ a Fe3+ Cytochromes, hydroxylases Mg2+ Glucose-6-phosphatase, hexokinase, DNA-polymerase Mn2+ Arginase Zn2+ Alcohol dehydrogenase, DNA polymerase, carbonic anhydrase Se Glutathion peroxidase FeS proteins (Fe2S2) NADH dehydrogenase, succinate dehydrogenase Ferredoxins • FeS proteins – Fe2S2, Fe4S4, transfer of electrons – redox reactions in the respiratory chain Metaloporphyrins - heme • compounds derived from the cyclic tetrapyrrole - porphyrin • complexes with metal ions – heme – Fe, transport of O2, transfer of electrons – chlorophyll – Mg2+ (Zn2+), photosynthesis Metaloporphyrins - cobalamin (vitamin B12) • chemically the most complex vitamin • structurally similar to heme – the centrally chelated metal is Co • in human 2 metabolically active forms: methylcobalamin and deoxyadenosylcobalamin • reactions – cytoplasmic methylation of homocysteine to methionine – mitochondrial methylmalonylCoA mutase reaction (methylmalonyl-CoA → succinyl-CoA)