3 FIGURE 14-1 Major pathways of glucose utilization FIGURE 14-1 Major pathways of glucose utilization. Although not the only possible fates for glucose, these four pathways are the most significant in terms of the amount of glucose that flows through them in most cells.
14 The nucleophilic attack of the C6—OH group of glucose on the g phosphate of an Mg2+–ATP complex. Page 585
15 The phosphoryl-transfer reaction catalyzed by hexokinase. Page 555
16 This same change in conformation is observed for ALL kinases! Conformation changes in yeast hexokinase on binding glucose. (a) Space-filling model of a subunit of free hexokinase. (b) Space-filling model of a subunit of free hexokinase in complex with glucose (purple).This same change inconformationis observed forALL kinases!It also accounts for thefact that water cannot beused for hydrolysis of ATPunless we fool the enzymeby using xylose instead of glc.\
18 Phosphoglucose isomerase (PGI) pKs for active site: 6.7 and 9.3(determined by rate vs. pH)Which aa’s??Actually Glu (!!!) and His with stabilization of His+ by a Glu(remember the ser protease mechanism!)
20 FIGURE 14-4 The phosphohexose isomerase reaction FIGURE 14-4 The phosphohexose isomerase reaction. The ring opening and closing reactions (steps 1 and 4) are catalyzed by an active-site His residue, by mechanisms omitted here for simplicity. The proton (pink) initially at C-2 is made more easily abstractable by electron withdrawal by the adjacent carbonyl and nearby hydroxyl group. After its transfer from C-2 to the active-site Glu residue (a weak acid), the proton is freely exchanged with the surrounding solution; that is, the proton abstracted from C-2 in step 2 is not necessarily the same one that is added to C-1 in step 3.
21 Phosphofructokinase (PFK) Works exactly like HK.Inhibited by hi [ATP]or citrateActivated by [AMP] even in the presence of hi [ATP].
24 FIGURE 14-5 The class I aldolase reaction FIGURE 14-5 The class I aldolase reaction. The reaction shown here is the reverse of an aldol condensation. Note that cleavage between C-3 and C-4 depends on the presence of the carbonyl group at C-2. A and B represent amino acid residues that serve as general acid (A) or base (B).
26 Figure 17-10 Proposed enzymatic mechanism of the TIM reaction: General Acid Catalysis. pKs = 6.5 and 9.5Like PGIBut pK1 is for GLU! Normal pk?4.1GluAsp activity by 1000!Reaction rate isdiffusion limited!!
27 End of Glycolysis Collection Phase Net result so far?ATPNAD+Carbon
28 FIGURE 14-6 Fate of the glucose carbons in the formation of glyceraldehyde 3-phosphate. (a) The origin of the carbons in the two three-carbon products of the aldolase and triose phosphate isomerase reactions. The end product of the two reactions is glyceraldehyde 3-phosphate (two molecules). (b) Each carbon of glyceraldehyde 3-phosphate is derived from either of two specific carbons of glucose. Note that the numbering of the carbon atoms of glyceraldehyde 3-phosphate differs from that of the glucose from which it is derived. In glyceraldehyde 3-phosphate, the most complex functional group (the carbonyl) is specified as C-1. This numbering change is important for interpreting experiments with glucose in which a single carbon is labeled with a radioisotope. (See Problems 6 and 9 at the end of this chapter.)
30 FIGURE NAD and NADP. (a) Nicotinamide adenine dinucleotide, NAD+, and its phosphorylated analog NADP+ undergo reduction to NADH and NADPH, accepting a hydride ion (two electrons and one proton) from an oxidizable substrate. The hydride ion is added to either the front (the A side) or the back (the B side) of the planar nicotinamide ring (see Table 13-8). (b) The UV absorption spectra of NAD+ and NADH. Reduction of the nicotinamide ring produces a new, broad absorption band with a maximum at 340 nm. The production of NADH during an enzyme-catalyzed reaction can be conveniently followed by observing the appearance of the absorbance at 340 nm (molar extinction coefficient ε340 = 6,200 M–1cm–1).
32 Some reactions employed in elucidating the enzymatic mechanism of GAPDH. (a) The reaction of iodoacetate with an active site Cys residue. (b) Quantitative tritium transfer from substrate to NAD+.Page 59632Pi also incorporated
49 The product’s composition, 3-phosphoglycerate From 3 to 2 position can readily mutateAnd now 2 phosphoglycerage does something rather strange—Electrons on and 3 proceed to rearrange.Thus, redox-dehydration, catalysed by enolaseGives PEP formation and bond energy raiseSo phosphoenolphruvate reacts with ADPThe kinase making ATP but NOT reversibly.In anaerobiosis, pyruvate’s not the end;The problem we suppose is not hard to comprehend’The dehydrogenation to phosphoglycerateWould grind to halt if NAD+ could not regenerate.The answer is quite subtle, pryruvayte is reduced,Instead of malate shuttle, L-lactate is produced;Lactate dehydrogenase performs that noble feat,NADH is oxidised; the pathway is complete.The balance sheet you’ll see shows transfer of energy,Two ATPs from glucose, and three from G1PThat’s good, but oh to use the way where pyruvate’s reduced—With decarboxylation first, then ethanol produced!!!!!