Section C - Enzymes

A related reaction that is known to proceed through acetyl-TDP is the previously mentioned bacterial pyruvate oxidase. As seen in Fig. 14-2, this enzyme has its own oxidant, FAD, which is ready to accept the two electrons of Eq. 14-22 to produce bound acetyl-TDP. The electrons may be able to jump directly to the FAD, with thiamin and flavin radicals being formed at an intermediate stage.1353 The electron transfers as well as other aspects of oxidative decarboxylation are discussed in Chapter 15, Section C. 

The molybdenum-containing enzymes considered in Section F also contain Fe-S clusters. Nitrogenases (Chapter 24) contain a more complex Fe-S-Mo cluster. Carbon monoxide dehydrogenase (Section C) contains 2 Ni, 11 Fe, and 14 S2 as well as Zn in a dimeric structure. In these enzymes the Fe-S clusters appear to participate in catalysis by undergoing alternate reduction and oxidation. 

The effects of ATP, AMP, and fructose 2,6-bisphos-phate on phosphofructokinase have been discussed in Chapter 11, Section C. Fructose 2,6-P2 is a potent allosteric activator of phosphofructokinase and a strong competitive inhibitor of fructose 1,6-bisphosphatase (Fig. 11-2). It is formed from fructose 6-P and ATP by the 90-kDa bifunctional phosphofructo-2-kinase/ fructose 2,6-bisphosphatase. Thus, the same protein forms and destroys this allosteric effector. Since the bifunctional enzyme is present in very small amounts, the rate of ATP destruction from the substrate cycling is small. 

In Chapter 11 the effects of binding of hormones to cell surface receptors have been emphasized. Equally important are the mechanisms that control the secretion of hormones. The topic of exocytosis has been considered briefly in Chapter 8, Section C,6 and aspects of the Golgi in Fig. 20-8 and associated text. Both hormones and neurotransmitters are secreted by exocytosis of vesicles. Cells have two pathways for secretion.386 387 The constitutive pathway is utilized for continuous secretion of membrane constituents, enzymes, growth factors, viral proteins, and components of the extracellular matrix. This pathway carries small vesicles that originate in the trans-Golgi network (TGN Fig. 20-8). The regulated pathway is utilized for secretion of hormones and neurotransmitters in response to chemical, electrical, or other stimuli. 

The crystal structures of the E Tyr and E Tyr-AMP complexes have also been solved.8 Although two moles of tyrosine bind to the crystalline enzyme, only one mole binds to the enzyme in solution. Further, only one mole of tyrosyl adenylate is formed rapidly per mole of dimer, and only one mole of tRNA is bound. The enzyme exhibits half-of-the-sites activity (Chapter 10, section C).9... 

A somewhat similar double cluster is present in all-Fe hydrogenases from Clostridium pasteurianum ° These enzymes also confain fwo or three Fe4S4 clusters and, in one case, an Fe2S2 cluster. At the presumed acbve site a special H cluster consists of an Fe3S4 cluster with one cysteine sulfur atom shared by an adjoining Fe2S2 cluster Because many hydrogenases contain nickel, their chemistry and fxmctions are discussed in Section C,2. 

N-acetylneuraminic acid protects the Intrinsic factor , a neuraminic add glycoprotein secreted by the mucous membrane of the stomach, against the action of proteol) c enzymes. The intrinsic factor binds vitamin B12 ingested with the food and allows its absorption in the lower sections of the intestine. The intrinsic factor still retains its ability to bind vitamin Bn after removal of the neuraminic acid, but the absorption of the vitamin from the intestinal lumen is no longer possible. 

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