《生物化学》课程PPT教学课件：英文版 Chapter 22 Biosynthesis of amino acids, nucleotides and related molecules

17 Amino acids are precursors of many specialized biomolecules Radioisotope tracer experiments showed that the porphyrin(卟啉) ring of the heme groups in mammals are made from 8 Gly and 8 succinyl-CoA (Glu in plants and bacteria) Deficiency of enzymes leading to heme biosynthesis cause diseases called porphyrias (The degradation of heme yields bilirubin, a linear tetrapyrrole derivative, and the typical pigments found in bile, urine, and feces, a deficiency of which will cause jaundice,黄疸)

17. Amino acids are precursors of many specialized biomolecules • Radioisotope tracer experiments showed that the porphyrin (卟啉)ring of the heme groups in mammals are made from 8 Gly and 8 succinyl-CoA (Glu in plants and bacteria). • Deficiency of enzymes leading to heme biosynthesis cause diseases called porphyrias. • (The degradation of heme yields bilirubin, a linear tetrapyrrole derivative, and the typical pigments found in bile, urine, and feces, a deficiency of which will cause jaundice，黄疸)

Creatine, the energy buffer in skeletal muscle, is made from Gly, Arg, and Met Glutathione, the "redox buffer", is derived from Glu 's. and Gly Indole-3-acetate ( or auxin), the plant growth hormone, is derived from Trp Many important neurotransmitters, e.g., g aminobutyrate(GABA), serotonin(5 norepinephrine, epinephrine are derived from e ne. hydroxytryptamine,or5HI,5-羟色胺), dopa acids via simple pathways: all include a Plp amino depedent decarboxylation reaction

• Creatine, the “energy buffer” in skeletal muscle, is made from Gly, Arg, and Met. • Glutathione, the “redox buffer”, is derived from Glu, Cys, and Gly. • Indole-3-acetate (or auxin), the plant growth hormone, is derived from Trp. • Many important neurotransmitters, e.g., g￾aminobutyrate (GABA), serotonin (5- hydroxytrptamine, or 5-HT, 5-羟色胺), dopamine, norepinephrine, epinephrine are derived from amino acids via simple pathways: all include a PLP￾depedent decarboxylation reaction

Polyamines(e.g, spermidine and spermine), needed for DNa packaging, is made from Met and ornithine Nitric oxide(NO), a stable free radical signals for vasodilation(血管舒张) in vertebrates, is made from the guanidino group of Arg and O, in a reaction catalyzed by an monooxygenase, nitric oxide synthase (NOs nos is a dimeric enzyme with each subunit containing an array of redox coenzymes: NADP FMN, FAD, tetrahydrobiopterin, and Fest-heme

• Polyamines (e.g., spermidine and spermine), needed for DNA packaging, is made from Met and ornithine. • Nitric oxide (NO), a stable free radical signals for vasodilation (血管舒张) in vertebrates, is made from the guanidino group of Arg and O2 in a reaction catalyzed by an monooxygenase, nitric oxide synthase (NOS). • NOS is a dimeric enzyme with each subunit containing an array of redox coenzymes: NADP, FMN, FAD, tetrahydrobiopterin, and Fe3+ -heme

COO Two molecules of 6-aminolevulinate CH2 Porphyrins Succinyl-COA C-S-CoA OoC CH%-Co0 IIn mammals are O CH, CH2 made from Gly Glycin COO CoA-SH m鬯来家 and succiny-CoA COo Four molecules of reactions I and 6 CH ③卜4NH occur in the mitochondria a-Amino-B C=0 ketoadipate the rest in the cytosols CH-NH s-aminolevulinate 4C02 COo synthase(main ⑥卜4CO2 ①CO2 control target for CH3 CH-CH COO heme biosynthesis) CH C=CH Ferrochelatase CH CHa-C-C C-CHa NH HN C=0 亚铁合 CH N C=C-CH=CHa tHeme CH, HC-C C-CH NHa F 8-Aminolevulinate δ-氨基—y-酮戊酸 CHo CH CH? Protoporphyrin IX 原卟

Porphyrins In mammals are made from Gly and succinyl-CoA (reactions 1 and 6 occur in the mitochondria, the rest in the cytosols) d-aminolevulinate synthase (main control target for heme biosynthesis) 胆色素原 原卟啉 d-氨基—g-酮戊酸 Heme Ferrochelatase 亚铁螯合酶 Fe2+

NH2 cOo creatine (酸),the“ energ. (CH2)3 CH-NH3 COO buffer in skeletal muscle. → Ornithine is derided from Gly, Arg, NH Gundinesetite and Met CH coo adoMet←[ Methionine adoHey NH C-NH2 N--CH, Creatine COo →ADP OeP-0 N--CHs CH Phosphocreatine

Creatine (肌酸), the “energy buffer” in skeletal muscle, is derivded from Gly, Arg, and Met

Cysteine Glycine ATP ADP+P ATP ADP+P Glutamate y-Glu-Cys-Gly y-glutamyl cysteine synthetase y-Glu-Cys glutathione synthetase Glutathione(GSH) Glutathione is Y-Glu VS Gly made from glu NH3 Cys, and gly OOC--CH-CH,-CH2-C-N--CH-C-N-CH2-CO0 H CH H GSH is probably important in SH maintaining proteins in their reduced Glutathione (GSH) (reduced) orms。 GSH is an important cofactor for Y-Glu-Cys-Gly glutathione peroxidase, an enzyme y-Glu-Cys-Gly containing an essential selenocysteine Glutathione(GSSG) (硒代半胱氨酸) residue in the active (oxidized) site, to remove toxic peroxides in cells

Glutathione is made from Glu, Cys, and Gly GSH is probably important in maintaining proteins in their reduced forms. •GSH is an important cofactor for glutathione peroxidase, an enzyme containing an essential selenocysteine (硒代半胱氨酸) residue in the active site, to remove toxic peroxides in cells

esike d GSH, having the structure of y-Glu-Cys-Gly is the redox buffer in cells, cycling between GSH (reduced form) and GSSg (oxidized form) The tripeptide is synthesized using specific enzymes(not ribosomes)

How is glutathione (GSH) synthesized? • GSH, having the structure of g-Glu-Cys-Gly, is the redox buffer in cells, cycling between GSH (reduced form) and GSSG (oxidized form); • The tripeptide is synthesized using specific enzymes (not ribosomes)

NH3 CHo-CH-COO Tryptophan transferase CH -COO Indole-3-pyruvate decarboxylaseCO2 The plant growth hormone, CHo-COO indole-3-acetate is derived from Trp. Indole-3-acetate (auxin (a)

The plant growth hormone, indole-3-acetate, is derived from Trp

NHs CHo-CH-CO0 OOC-CHg-CH2-CH-COo CH9-CH-COo Glutamate Tetrahydrobiopterin cutan PLP Og HO Tetrahydrobiopterin HO NHs 0OC-CH2-CHg-CH, HO Y-Aminobutyrate Dihydrobiopterin CH2-CH-Coo (GABA) NHs CH,-CH-CO0 →CO LiH- CH2- HO 5-Hydroxytryptophan NHa N NH HO CHo-CH Histidin learns and PLP Dopamine cOz PLP →C O2 H,O HO Dehydroascorbate HO CH2-CH2 N NH CH-CH2 Histamine Norepinephrine adoMet H Many neurotransmitters are CH-CH2 Epinephrine derived from amino acids

Many neurotransmitters are derived from amino acids

COo ATP PP,+ P H3N-C-H S-Adenosylmethionine Methionine CHe *s-Adenosine CH domE PLP H3N--CH2-CH2-CH2-CH-CO0 Ornithine decarboxylase N→Co2 PLP ormithine cO2 H3N-CH2 " CH H3N-(CH2)4-NH3 Putrescine H propylaminotransferase - Adenosine →CH3-S- Adenosine CH3 Methylthioadenosine Decarboxylated adoMet H3N-(CH2)3-NH-(CH)4-NH3 Spermidine propylaminotransferase II →CH3-S- Adenosine Spermidine and spermine HgN-(CH2)3-NH-(CH2)4-NH-(CH2)3-NHs are derived from met perming and ornithine

Spermidine and spermine are derived from Met and ornithine