influence of pH on the activity of yeast ADH: Find and read the sources listed in the file attached to Question 16 to learn more about yeast alcohol dehydrogenase (ADH) from the research literature. Fill in the gaps with the correct numbers, words or phrases from the list provided below for this question, to discuss what is known about the catalytic mechanism of yeast ADH and how the pH of the reaction medium can influence the activity of yeast ADH. Some words, phrases or numbers may be used more than once and others not at all. The spelling must be correct, otherwise the automatic marking system will not recognise the words used. For catalysis to occur, the of the ADH enzyme must bind a molecule of coenzyme and a molecule of substrate and catalyse a hydride transfer reaction between them (Leskovac et al., 2002). The alcohol binds to the enzyme-NAD+ complex and is to the corresponding carbonylic compound through a system in a hydrogen-bonded network that involves the zinc-bound alcohol, the hydroxyl group of a side chain, a hydroxyl group from the nicotinamide ribose and the imidazole group of a histidine residue on the surface of the enzyme, His-51 (Leskovac et al., 2002; Raj et al., 2014). Numerous amino acid residues are involved in substrate and coenzyme binding and in catalysis, which means that their functional groups must be in the appropriate state of for substrate and coenzyme binding and subsequent catalysis of the reaction to occur. A recent study by Plapp et al. (2016) suggested that the yeast ADH subunits found in open conformation are in an intermediate state, which can bind the coenzyme and the substrate, before the induced changes to the closed conformation occur. The is the state required for the actual oxidation of the hydroxylic group in the substrate (Plapp et al., 2016). The reduction in yeast ADH activity at pH values lower than optimal is likely to be due to impaired while at pH values higher than the optimal it is likely to be due to impaired and catalysis, due to changes in the ionisation state of the main functional groups involved in each case _for substrate binding and for NAD+ binding), which have different pka values (Silverstein, 2016). List of words, phrases and numbers: active site; closed conformation, coenzyme binding; Cys-46; Cys-100; electron relay, His-30; His-51; histidine, ionisation; Lys-228; Lys-328; open conformation; oxidised; proton relay, protonation; reduced; substrate binding, threonine, zinc
