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· Glycolysis is the __. This process is __because it evolved before oxygen was present.
o Pyruvate can be processed to __ or __ or, under aerobic conditions, __, generating much more __
sequence of reactions that metabolizes one molecule of glucose to two molecules of pyruvate with the concomitant net production of two molecules of ATP
anaerobic
lactate or ethanol
completely oxidized to CO2
ATP
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· Because glucose is important, metabolic products are salvaged to synthesize glucose in the process of __, which is not the reverse of glycolysis
· The two pathways are __ so that what?
- gluconeogenesis
- reciprocally regulated
- glycolysis and gluconeogenesis do not take place simultaneously in the same cell to a significant extent
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· When taking in starch and glycogen, they are digested by the pancreatic enzyme __ and __, which cleaves the __ of starch and glycogen, but not the __.
o Material that is not digestbile because of the 1,6 bonds is called the __
alpha-amylase and salivary alpha-amylase
alpha-1,4 bonds
alpha- 1,6 bonds
limit dextrin
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· __cleaves maltose into two glucose molecules, whereas __ digests __and any other oligosaccharides that may have escaped by digestion by the amylase
o __ further digests the __
· Both __ and __ are located on the surface of the intestinal cells, as is sucrose
- Maltase
- alpha-glucosidase
- maltotriose
- Alpha-dextrinase
- limit dextrin
- maltase and alpha-dextrinase
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· __is the only fuel the brain uses under nonstarvation conditions and the only fuel that __ can use. It is the prominent fuel because:
o __
o Low tendency to __; can exist in the __ and relatively little tendency to modify proteins
1) It is a monoscchride formed form formaldehyde under prebiotic conditions; readily available
2) nonenzymatically glycosylate proteins; ring conformation
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· The glycolytic pathway is common to virtally all cells and comprises two stages
Explain stage 1
trapping and prep phase; no ATP generation
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How does stage one begin?
§ Begins with conversion of glucose into fructose 1,6-bisphosphate, which has three steps: phosphorylation, isomerization, and another phosphorylation
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What is the strategy of step one?
§ Strategy is to trap glucose in the cell and form a compound that can be cleaved into phosphorylated three-carbon units
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How is stage one completed?
§ Completed with cleavage of fructose 1,6-bisphosphate into two three-carbon fragments, which are readily interconvertible
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What is stage 2 of glycolysis?
o Stage 2: ATP is harvested when the three-carbon fragments are oxidized to pyruvate
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· Glucose enters cells through __ and is phosphorylated by ATP to form __, which is notable for two reasons:
o Reason one?
o Reason two?
specific transport phrteins
glucose 6-phosphate
Glucose 6-phosphate cannot pass through the membrane because it is not a substrate for the glucose transporters
The addition of the phosphoryl group acts to destabilize glucose, thus facilitating its further metabolism
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· The transfer of the phosphoryl group from ATP to the hydroxyl group on carbon 6 of glucose is catalyzed by __; t requires __ for activity, which forms a complex with __
o The binding of glucose induces a __ in the enzyme. __has __, which do what when glucose is bound
- hexokinase
- Mg or another divalent metal ion
- ATP
- large conformational change in
- Hexokinase
- two lobes
- move toward each other
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§ On glucose binding, one lobe __ with respect to the other, resulting in movements of the __
§ The __between the lobes __, and the bound glucose becomes surrounded by __,e xcept for the __, which will accept the __ from __
§ The closing of the cleft in hexokinase is an example of __
- rotates 12 degrees
- polypeptide backbone of as much as 8 angstroms
- cleft
- closes
- protein
- hydroxyl group of carbon 6
- phosphoryl group
- ATP
- induced fit
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o These changes that hexokinase undergoes are significant for two reasons:
Reason 1?
§ First, the environment around the glucose becomes more nonpolar, which favors reaction between the hydrophilic hydroxyl group of glucose and the terminal phosphoryl group of ATP
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o These changes that hexokinase undergoes are significant for two reasons:
Reason 2?
- § Second, the conformational changes enable the kinase to discriminate against H2O as a substrate; closing the cleft keeps water away from the active site
- · A rigid kinase would be an ATPase as well
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__ is a general future of kinases.
o Substrate-induced cleft closing is a general feature of kinases
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· The second step is the __, which is a conversion of an __into a __.
o The reaction catalyzed by __ takes seeral steps due to the necessity to __, __, and __.
isomerization of glucose 6-phosphate to fructose 6- phosphate
aldose
ketose
phosphoglucose isomerase
open the rings, isomerize, and reform the ring of the product
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· A second __follows this __: __ is phosphorylated at the expense of ATP to __, catalyzed y __, an allosteric enzyme that sets the pace of glycolysis
·
- phosphorylation
- isomerization
- Fructose 6-phosphate
- fructose 1, 6 bisphosphate
- phosphofructokinase
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Fructose 1, 6 bisphosphate is cleaved into __ and __, completing stage 1 of glycolysis, catalyzed by aldolase
o __can move on to the next step, but __cannot; and so, it is isomerized by __, which is rapid and reversible.
glyceralehyde 3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP)
- GAP
- DHAP
- triose phosphate isomerase
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· In summary: __to the ketose fructose followed by __ yields two phosphorylated interconvertable 3-carbon fragments that can oxidized later to __ via __
- isomerization
- aldol cleavage
- capture energy via ATP
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· LOOK CLOSER: Triose phosphate isomerase catalyzes the__. The isomerization of a __ into an __ proceeds through an __
o __ plays the role of a __: it does what from C1 and donates it to C2. But, the carboxylate group of glutamate 165 by itself is not basic enough to __; assisted by __, which does what to stabilize the negative charge that develops on the C2 carbonyl group
transfer of a hydrogen atom from C1 to C2, an intramolecular oxidation-reduction
- ketose
- aldose
- enediol intermediate
- Glutamate 165
- general acid-base catalyst
- abstracts a proton
- pull a proton away from the carbon of the carbonyl
- hisitine 95
- donates a proton
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· Features of TPI
o Displays great catalytic prowess (isomerizes by 1010); catalysis takes place every time the __; __is rate limiting; it is a __
o It suppresses an undesired side reaction, the __, which is 100 times as fast as isomerization
§ __ is reactive and can modify the structure and function of several biomolecules
- enzyme and substrate meet
- diffusion
- kinetically perfect enzyme
- decomposition of the enediol intermediate into methyl glyoxal and orthophosphate
- Methyl glyoxal
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· So, TPI prevents the __from leaving the membrane
It is trapped by the __, which serves as a lid on the active site, shutting it when the enediol is present and reopening it when __is completed; active site remains __until __takes place
- enediol
- movement of a loop of 10 residues
- isomerization
- closed
- isomerization
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· AT the end of the first stage, __molecules of ATP have been invested.
two
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