CHAPTER 26: INTERMEDIATE REACTIONS IN ANAEROBIC GLYCOLYSIS
Chapter 26: Intermediate Reactions in Anaerobic Glycolysis
The intermediate reactions in anaerobic glycolysis begin by cleavage of the hexose fructose 1,6-bisphosphate (Frc-1,6-bisP) into two triose phosphates (i.e., dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3- phosphate (Gl-3-P). These phosphorylated intermediates are ultimately used to harvest ATP as they proceed through a series of reactions that oxidize them to pyruvate.
The conversion of Frc-1,6-bisP to Gl-3-P and DHAP is catalyzed by aldolase (reaction #8), a zinc-containing enzyme. This is the only degradative step in the EMP involving a C-C bond. The DHAP and Gl-3-P generated can also be readily interconverted by the enzyme triosephosphate isomerase (#9). The equilibrium of this reaction strongly favors Gl-3-P formation since this compound is continually being phosphorylated to 1,3- bisphosphoglycerate (1,3-bisPG; reaction #15). Fructose 1-phosphate (Frc-1-P), derived from dietary fructose or from the Polyol Pathway, can also be split into glyceraldehyde and DHAP by aldolase (#10). Next, glyceraldehyde can gain access to the EMP via another enzyme present in liver, triokinase (#11), which catalyzes the phosphorylation of glyceraldehyde to glyceraldehyde 3-phosphate (Gl-3-P). Additionally, glyceraldehyde can be acted upon by glyceraldehyde dehydrogenase (#12) to form glycerate, and then glycerate kinase (#13) will catalyze formation of 3-phosphoglycerate (3-PG) from glycerate. Dihydroxyacetone phosphate also serves as a precursor to glycerol 3-phosphate, particularly in adipose tissue, a reaction catalyzed by glycerol 3-P dehydrogenase (#14, see "Phosphatidic Acid Pathway"). Since NAD+ must be regenerated in order for glycolysis to continue, and since both DHAP and glycerol 3-P are permeable to mitochondrial membranes (where NADH is not), these two compounds sometimes participate in the "glycerol 3-P shuttle", where electrons from NADH (rather than NADH itself) are carried across mitochondrial membranes. Glycerol (derived from glycerol 3-P) serves as the backbone for triglycerides and most phospholipids, and it also enters the hepatic gluconeogenic pathway at the level of glycerol 3-P.
Glycolysis proceeds by the oxidation of Gl-3- P to 1,3-bisphosphoglycerate (1,3-bisPG; also called 1,3-diphosphoglycerate (1,3-DPG)), catalyzed by the enzyme Gl-3-P dehydrogenase (#15); and, because of the activity of triosephosphate isomerase, DHAP can be oxidized to 1,3-bisPG via Gl-3-P. (Note that reaction #15 uses inorganic phosphate (Pi), not ATP, and NAD+ is required, thus forming NADH). As stated previously, during anaerobic glycolysis, NAD+ must be continuously generated for this reaction in order to permit the EMP to continue. Oxidation of NADH is carried out by either coupling to the pyruvate —> lactate, or pyruvate —> alanine reactions in the cytosol, or by coupling to the DHAP —> glycerol 3-P (#14), or oxaloacetate —> malate reactions, where electrons from NADH, rather than NADH itself, are carried across mitochondrial membranes to enter oxidative phosphorylation. Also note that two molecules of 1,3-bisPG have been generated at this point from 1 molecule of glucose. This reaction is freely reversible in the liver, and is used in both glycolysis and gluconeogenesis.
The high energy phosphate bond formed during the previous reaction (#15) is next transferred to ADP during the formation of 3-PG from 1,3-bisPG, catalyzed by the enzyme phosphoglycerate kinase (#16). This is the first site of ATP production in the EMP. Since two molecules of triose phosphate were formed per molecule of glucose undergoing glycolysis, 2 ATPs are generated at this stage per molecule of glucose. This reaction is a substrate-level phosphorylation, a term used to refer to a process in which a substrate participates in an enzyme-catalyzed reaction that yields ATP (or GTP). A phosphate is transferred in this reaction from a high-energy compound (i.e., 1,3-bisPG), that is not a nucleotide. This stands in contrast to oxidative phosphorylation in which electron transport by the respiratory chain of the mitochondrial inner membrane is used to provide the energy necessary for ATP synthesis. Although this reaction provides a means for the generation of ATP in anaerobic glycolysis, it can also be used in the reverse direction for the synthesis of 1,3-bisPG at the expense of ATP when hepatic gluconeogenesis is being stimulated.
In erythrocytes of several mammalian species, diphosphoglyceromutase (#17) catalyzes formation of an important intermediate product in this reaction (2,3-bisphosphoglycerate (2,3- bisPG, also called 2,3-diphosphoglycerate (2,3-DPG)), which reduces the hemoglobin binding affinity for oxygen. Note that this step effectively bypasses reaction #16, and dissipates as heat the free energy associated with the high-energy phosphate of 1,3-bisPG. This loss of high-energy phosphate, which means that there is no net production of ATP when glycolysis takes this "Rapoport Shunt", may be of advantage to the economy of the erythrocyte since it would allow glycolysis to proceed when the need for ATP was minimal. The 2,3-DPG formed in erythrocytes can return to the EMP following a dephosphorylation reaction (#18).
The next reaction in anaerobic glycolysis involves phosphoglyceromutase (#19), an enzyme that transfers the phosphate from position 3 of 3-PG to position 2, thus forming 2- phosphoglycerate (2-PG). This sets up the production of another high-energy phosphate, as well as more ATP two reactions later.
Enolase (#20) catalyzes the dehydration of 2- PG to phosphoenolpyruvate (PEP), another high-energy compound. This is a remarkable reaction from the standpoint that a high-energy phosphate compound is generated from one with a markedly lower energy level. Although this reaction is freely reversible, a large change in the distribution of energy occurs as a consequence of the action of enolase upon 2-PG. Enolase is inhibited by fluoride (F–), a property that is made use of by adding F– to collected blood to inhibit erythrocytic glycolysis prior to estimation of the plasma glucose concentration.
As anaerobic glycolysis continues, the high-energy phosphate of PEP is transferred to ADP by the enzyme pyruvate kinase (#21), to generate 2 more moles of ATP (per mole of glucose oxidized), and pyruvate. This is another substrate level phosphorylation that is accompanied by considerable loss of free energy as heat. However, unlike reaction #16, conversion of PEP to pyruvate is physiologically irreversible. Hepatic pyruvate kinase is activated by Frc-1,6-bisP (feed-forward activation), and inhibited by alanine and ATP. Pyruvate kinase in muscle is not affected by Frc-1,6-bisP, but it is inhibited by phosphocreatine and activated by a drop in the ATP/ADP ratio. The difference in the kinetics and regulation of these two isoenzymes reflects the fact that liver is a gluconeogenic organ, whereas muscle is not.
Anaerobic glycolysis gives a net yield of two ATP in the conversion of one glucose to two pyruvate molecules. One ATP is used in the hexokinase reaction, one is used in the PFK reaction, and two ATPs per glucose molecule are generated at the phosphoglycerate kinase and two at the pyruvate kinase reactions (a total of four ATPs generated and two utilized). Anaerobic glycolysis can give a net yield of three ATP when the glucose 6-phosphate residue comes from intracellular glycogen (since the hexokinase reaction, which uses one ATP, may not be utilized). If aerobic conditions prevail and pyruvate is allowed to move into mitochondria for acetyl-CoA or oxaloacetate formation, then reducing equivalents from the two NADH generated in the conversion of Gl-3-P to 1,3-bisPG (reaction #15) can be shuttled into mitochondria for ATP formation. Since three ATP are generated in the mitochondrial respiratory chain for each molecule of NADH which enters, a total of six ATP can be generated from cytoplasmic production of NADH during the oxidation of one glucose molecule. This brings the total to 8 ATP molecules derived (both directly and indirectly) from the cytoplasmic portion of glucose oxidation, or 9 from each molecule of glucose 6-phosphate derived directly from glycogen. The mitochondrial portion of aerobic glucose combustion, however, can yield 30 ATP equivalents from the complete oxidation of 2 pyruvate molecules through acetyl-CoA, thus bringing the total possible ATP equivalents derived from the complete aerobic oxidation of 1 molecule of glucose to 38. If pyruvate, however, is being converted to oxaloacetate rather than acetyl-CoA (e.g., during fat oxidation in muscle tissue), then this number would be reduced to 30 ATP equivalents.
With one mol of glucose approximating 686 Kcal worth of energy, and one ATP high-energy phosphate bond being equal to about 7.6 Kcal, it follows that approximately 42% of the energy of glucose is captured in the form of ATP during complete aerobic combustion. The remaining energy in glucose escapes as heat, which aids in the regulation of body temperature. Of course, eventually all energy derived from glucose oxidation is released as heat after ATP is used up while serving its numerous purposes.
SUMMARY
Chapter 26 discusses the intermediate reactions in anaerobic glycolysis. The process begins with the cleavage of fructose 1,6-bisphosphate into two triose phosphates, DHAP and Gl-3-P. These intermediates are then oxidized to pyruvate, generating ATP. The conversion of fructose 1,6-bisphosphate to DHAP and Gl-3-P is catalyzed by aldolase, and the two can be interconverted by triosephosphate isomerase. Glyceraldehyde can enter the glycolysis pathway through triokinase, and it can also be converted to glycerate and then 3-phosphoglycerate by glyceraldehyde dehydrogenase and glycerate kinase. DHAP and glycerol 3-phosphate can participate in the glycerol 3-P shuttle to regenerate NAD+ for glycolysis. The oxidation of Gl-3-P to 1,3-bisphosphoglycerate is catalyzed by Gl-3-P dehydrogenase, and this reaction requires NAD+. NADH can be oxidized through various reactions to regenerate NAD+ for glycolysis. Phosphoglycerate kinase catalyzes the transfer of a high-energy phosphate bond from 1,3-bisphosphoglycerate to ADP, generating ATP. Enolase dehydrates 2-phosphoglycerate to form phosphoenolpyruvate, another high-energy compound. Pyruvate kinase transfers the high-energy phosphate of phosphoenolpyruvate to ADP, generating ATP and pyruvate. Anaerobic glycolysis yields a net of two ATP per glucose molecule. Under aerobic conditions, NADH can be shuttled into mitochondria for ATP production, resulting in a total of 8 ATP molecules derived from cytoplasmic glucose oxidation. The complete aerobic oxidation of glucose can yield up to 38 ATP equivalents. The remaining energy in glucose is released as heat.
OUTLINE
Anaerobic glycolysis begins with the cleavage of fructose 1,6-bisphosphate (Frc-1,6-bisP) into dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (Gl-3-P) by aldolase.
DHAP and Gl-3-P can be interconverted by triosephosphate isomerase.
Fructose 1-phosphate (Frc-1-P) can also be split into glyceraldehyde and DHAP by aldolase.
Glyceraldehyde can enter the glycolysis pathway via triokinase, which phosphorylates it to glyceraldehyde 3-phosphate (Gl-3-P).
Glyceraldehyde can also be converted to glycerate by glyceraldehyde dehydrogenase, and then to 3-phosphoglycerate (3-PG) by glycerate kinase.
DHAP and glycerol 3-phosphate can participate in the "glycerol 3-P shuttle" to regenerate NAD+ in the mitochondria.
Glycolysis proceeds by oxidizing Gl-3-P to 1,3-bisphosphoglycerate (1,3-bisPG) via Gl-3-P dehydrogenase.
NADH generated in glycolysis can be oxidized by various reactions to regenerate NAD+.
Phosphoglycerate kinase transfers the high-energy phosphate bond from 1,3-bisPG to ADP, generating ATP.
Enolase dehydrates 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP), another high-energy compound.
Pyruvate kinase transfers the high-energy phosphate of PEP to ADP, generating ATP and pyruvate.
Anaerobic glycolysis yields a net of two ATP per glucose molecule.
Under aerobic conditions, NADH can enter the mitochondrial respiratory chain to generate ATP.
The complete aerobic oxidation of glucose can yield up to 38 ATP equivalents.
Approximately 42% of the energy from glucose is captured as ATP during aerobic combustion, with the remaining energy released as heat.
QUESTIONS
Qcard 1:
Question: What are the intermediate reactions in anaerobic glycolysis?
Answer: The intermediate reactions in anaerobic glycolysis involve the cleavage of fructose 1,6-bisphosphate (Frc-1,6-bisP) into dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (Gl-3-P).
Qcard 2:
Question: What enzyme catalyzes the conversion of Frc-1,6-bisP to Gl-3-P and DHAP?
Answer: Aldolase catalyzes the conversion of Frc-1,6-bisP to Gl-3-P and DHAP.
Qcard 3:
Question: What is the role of triosephosphate isomerase in anaerobic glycolysis?
Answer: Triosephosphate isomerase interconverts DHAP and Gl-3-P, with a strong favor towards Gl-3-P formation.
Qcard 4:
Question: How is glyceraldehyde 3-phosphate (Gl-3-P) formed in anaerobic glycolysis?
Answer: Glyceraldehyde can be phosphorylated to Gl-3-P by the enzyme triokinase.
Qcard 5:
Question: What is the first site of ATP production in the EMP?
Answer: The formation of 3-phosphoglycerate (3-PG) from 1,3-bisphosphoglycerate (1,3-bisPG) catalyzed by phosphoglycerate kinase is the first site of ATP production in the EMP.
Qcard 6:
Question: What is the role of enolase in anaerobic glycolysis?
Answer: Enolase catalyzes the dehydration of 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP), another high-energy compound.
Qcard 7:
Question: What enzyme catalyzes the conversion of PEP to pyruvate in anaerobic glycolysis?
Answer: Pyruvate kinase catalyzes the conversion of PEP to pyruvate, generating two moles of ATP per mole of glucose oxidized.
Qcard 8:
Question: How many ATP molecules are generated in anaerobic glycolysis from the conversion of one glucose molecule?
Answer: Anaerobic glycolysis generates a net yield of
Cleavage of Fructose 1,6-bisphosphate
Interconversion of DHAP and Gl-3-P
Entry of Glyceraldehyde into EMP
Glycerol 3-P Shuttle
Oxidation of Gl-3-P to 1,3-bisPG
Formation of 3-PG from 1,3-bisPG
Dehydration of 2-PG to PEP
Conversion of PEP to Pyruvate
Aldolase catalyzes the conversion of Frc-1,6-bisP to Gl-3-P and DHAP.
Triosephosphate isomerase interconverts DHAP and Gl-3-P.
Aldolase splits Frc-1-P into glyceraldehyde and DHAP.
Triokinase phosphorylates glyceraldehyde to Gl-3-P.
Glycerol 3-P dehydrogenase converts DHAP to glycerol 3-phosphate.
Glycerol 3-phosphate participates in the glycerol 3-P shuttle to regenerate NAD+.
Gl-3-P dehydrogenase oxidizes Gl-3-P to 1,3-bisPG, generating NADH.
Phosphoglycerate kinase transfers the high-energy phosphate from 1,3-bisPG to ADP, generating ATP.
Enolase catalyzes the dehydration of 2-PG to PEP.
Read and understand the overall process of anaerobic glycolysis.
Focus on the cleavage of fructose 1,6-bisphosphate (Frc-1,6-bisP) into dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (Gl-3-P) by aldolase (#8).
Study the interconversion of DHAP and Gl-3-P by triosephosphate isomerase (#9).
Learn about the formation of 1,3-bisphosphoglycerate (1,3-bisPG) from Gl-3-P (#15).
Review the conversion of fructose 1-phosphate (Frc-1-P) to glyceraldehyde and DHAP by aldolase (#10).
Understand the role of triokinase (#11) in phosphorylating glyceraldehyde to Gl-3-P.
Study the formation of glycerate from glyceraldehyde by glyceraldehyde dehydrogenase (#12).
Learn about the catalysis of 3-phosphoglycerate (3-PG) formation from glycerate by glycerate kinase (#13).
Focus on the role of dihydroxyacetone phosphate as a precursor to glycerol 3-phosphate and its catalysis by glycerol 3-P dehydrogenase (#14).
Understand the importance of NAD+ regeneration and the involvement of DHAP and glycerol 3-P in the "glycerol 3-P shuttle".
Study the oxidation of glyceraldehyde 3-phosphate to 1,3-bisPG by glyceraldehyde 3-P dehydrogenase (#15).
Review the transfer of the high-energy phosphate bond from 1,3-bisPG to ADP by phosphoglycerate kinase (#16) for ATP production.
Understand the role of diphosphoglyceromutase (#17) in the formation of 2,3-bisphosphoglycerate (2,3-bisPG) in erythrocytes.
Study the transfer of phosphate from position 3 of 3-PG to position 2 by phosphoglyceromutase (#19)
Chapter 26: Intermediate Reactions in Anaerobic Glycolysis
The intermediate reactions in anaerobic glycolysis begin by cleavage of the hexose fructose 1,6-bisphosphate (Frc-1,6-bisP) into two triose phosphates (i.e., dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3- phosphate (Gl-3-P). These phosphorylated intermediates are ultimately used to harvest ATP as they proceed through a series of reactions that oxidize them to pyruvate.
The conversion of Frc-1,6-bisP to Gl-3-P and DHAP is catalyzed by aldolase (reaction #8), a zinc-containing enzyme. This is the only degradative step in the EMP involving a C-C bond. The DHAP and Gl-3-P generated can also be readily interconverted by the enzyme triosephosphate isomerase (#9). The equilibrium of this reaction strongly favors Gl-3-P formation since this compound is continually being phosphorylated to 1,3- bisphosphoglycerate (1,3-bisPG; reaction #15). Fructose 1-phosphate (Frc-1-P), derived from dietary fructose or from the Polyol Pathway, can also be split into glyceraldehyde and DHAP by aldolase (#10). Next, glyceraldehyde can gain access to the EMP via another enzyme present in liver, triokinase (#11), which catalyzes the phosphorylation of glyceraldehyde to glyceraldehyde 3-phosphate (Gl-3-P). Additionally, glyceraldehyde can be acted upon by glyceraldehyde dehydrogenase (#12) to form glycerate, and then glycerate kinase (#13) will catalyze formation of 3-phosphoglycerate (3-PG) from glycerate. Dihydroxyacetone phosphate also serves as a precursor to glycerol 3-phosphate, particularly in adipose tissue, a reaction catalyzed by glycerol 3-P dehydrogenase (#14, see "Phosphatidic Acid Pathway"). Since NAD+ must be regenerated in order for glycolysis to continue, and since both DHAP and glycerol 3-P are permeable to mitochondrial membranes (where NADH is not), these two compounds sometimes participate in the "glycerol 3-P shuttle", where electrons from NADH (rather than NADH itself) are carried across mitochondrial membranes. Glycerol (derived from glycerol 3-P) serves as the backbone for triglycerides and most phospholipids, and it also enters the hepatic gluconeogenic pathway at the level of glycerol 3-P.
Glycolysis proceeds by the oxidation of Gl-3- P to 1,3-bisphosphoglycerate (1,3-bisPG; also called 1,3-diphosphoglycerate (1,3-DPG)), catalyzed by the enzyme Gl-3-P dehydrogenase (#15); and, because of the activity of triosephosphate isomerase, DHAP can be oxidized to 1,3-bisPG via Gl-3-P. (Note that reaction #15 uses inorganic phosphate (Pi), not ATP, and NAD+ is required, thus forming NADH). As stated previously, during anaerobic glycolysis, NAD+ must be continuously generated for this reaction in order to permit the EMP to continue. Oxidation of NADH is carried out by either coupling to the pyruvate —> lactate, or pyruvate —> alanine reactions in the cytosol, or by coupling to the DHAP —> glycerol 3-P (#14), or oxaloacetate —> malate reactions, where electrons from NADH, rather than NADH itself, are carried across mitochondrial membranes to enter oxidative phosphorylation. Also note that two molecules of 1,3-bisPG have been generated at this point from 1 molecule of glucose. This reaction is freely reversible in the liver, and is used in both glycolysis and gluconeogenesis.
The high energy phosphate bond formed during the previous reaction (#15) is next transferred to ADP during the formation of 3-PG from 1,3-bisPG, catalyzed by the enzyme phosphoglycerate kinase (#16). This is the first site of ATP production in the EMP. Since two molecules of triose phosphate were formed per molecule of glucose undergoing glycolysis, 2 ATPs are generated at this stage per molecule of glucose. This reaction is a substrate-level phosphorylation, a term used to refer to a process in which a substrate participates in an enzyme-catalyzed reaction that yields ATP (or GTP). A phosphate is transferred in this reaction from a high-energy compound (i.e., 1,3-bisPG), that is not a nucleotide. This stands in contrast to oxidative phosphorylation in which electron transport by the respiratory chain of the mitochondrial inner membrane is used to provide the energy necessary for ATP synthesis. Although this reaction provides a means for the generation of ATP in anaerobic glycolysis, it can also be used in the reverse direction for the synthesis of 1,3-bisPG at the expense of ATP when hepatic gluconeogenesis is being stimulated.
In erythrocytes of several mammalian species, diphosphoglyceromutase (#17) catalyzes formation of an important intermediate product in this reaction (2,3-bisphosphoglycerate (2,3- bisPG, also called 2,3-diphosphoglycerate (2,3-DPG)), which reduces the hemoglobin binding affinity for oxygen. Note that this step effectively bypasses reaction #16, and dissipates as heat the free energy associated with the high-energy phosphate of 1,3-bisPG. This loss of high-energy phosphate, which means that there is no net production of ATP when glycolysis takes this "Rapoport Shunt", may be of advantage to the economy of the erythrocyte since it would allow glycolysis to proceed when the need for ATP was minimal. The 2,3-DPG formed in erythrocytes can return to the EMP following a dephosphorylation reaction (#18).
The next reaction in anaerobic glycolysis involves phosphoglyceromutase (#19), an enzyme that transfers the phosphate from position 3 of 3-PG to position 2, thus forming 2- phosphoglycerate (2-PG). This sets up the production of another high-energy phosphate, as well as more ATP two reactions later.
Enolase (#20) catalyzes the dehydration of 2- PG to phosphoenolpyruvate (PEP), another high-energy compound. This is a remarkable reaction from the standpoint that a high-energy phosphate compound is generated from one with a markedly lower energy level. Although this reaction is freely reversible, a large change in the distribution of energy occurs as a consequence of the action of enolase upon 2-PG. Enolase is inhibited by fluoride (F–), a property that is made use of by adding F– to collected blood to inhibit erythrocytic glycolysis prior to estimation of the plasma glucose concentration.
As anaerobic glycolysis continues, the high-energy phosphate of PEP is transferred to ADP by the enzyme pyruvate kinase (#21), to generate 2 more moles of ATP (per mole of glucose oxidized), and pyruvate. This is another substrate level phosphorylation that is accompanied by considerable loss of free energy as heat. However, unlike reaction #16, conversion of PEP to pyruvate is physiologically irreversible. Hepatic pyruvate kinase is activated by Frc-1,6-bisP (feed-forward activation), and inhibited by alanine and ATP. Pyruvate kinase in muscle is not affected by Frc-1,6-bisP, but it is inhibited by phosphocreatine and activated by a drop in the ATP/ADP ratio. The difference in the kinetics and regulation of these two isoenzymes reflects the fact that liver is a gluconeogenic organ, whereas muscle is not.
Anaerobic glycolysis gives a net yield of two ATP in the conversion of one glucose to two pyruvate molecules. One ATP is used in the hexokinase reaction, one is used in the PFK reaction, and two ATPs per glucose molecule are generated at the phosphoglycerate kinase and two at the pyruvate kinase reactions (a total of four ATPs generated and two utilized). Anaerobic glycolysis can give a net yield of three ATP when the glucose 6-phosphate residue comes from intracellular glycogen (since the hexokinase reaction, which uses one ATP, may not be utilized). If aerobic conditions prevail and pyruvate is allowed to move into mitochondria for acetyl-CoA or oxaloacetate formation, then reducing equivalents from the two NADH generated in the conversion of Gl-3-P to 1,3-bisPG (reaction #15) can be shuttled into mitochondria for ATP formation. Since three ATP are generated in the mitochondrial respiratory chain for each molecule of NADH which enters, a total of six ATP can be generated from cytoplasmic production of NADH during the oxidation of one glucose molecule. This brings the total to 8 ATP molecules derived (both directly and indirectly) from the cytoplasmic portion of glucose oxidation, or 9 from each molecule of glucose 6-phosphate derived directly from glycogen. The mitochondrial portion of aerobic glucose combustion, however, can yield 30 ATP equivalents from the complete oxidation of 2 pyruvate molecules through acetyl-CoA, thus bringing the total possible ATP equivalents derived from the complete aerobic oxidation of 1 molecule of glucose to 38. If pyruvate, however, is being converted to oxaloacetate rather than acetyl-CoA (e.g., during fat oxidation in muscle tissue), then this number would be reduced to 30 ATP equivalents.
With one mol of glucose approximating 686 Kcal worth of energy, and one ATP high-energy phosphate bond being equal to about 7.6 Kcal, it follows that approximately 42% of the energy of glucose is captured in the form of ATP during complete aerobic combustion. The remaining energy in glucose escapes as heat, which aids in the regulation of body temperature. Of course, eventually all energy derived from glucose oxidation is released as heat after ATP is used up while serving its numerous purposes.
SUMMARY
Chapter 26 discusses the intermediate reactions in anaerobic glycolysis. The process begins with the cleavage of fructose 1,6-bisphosphate into two triose phosphates, DHAP and Gl-3-P. These intermediates are then oxidized to pyruvate, generating ATP. The conversion of fructose 1,6-bisphosphate to DHAP and Gl-3-P is catalyzed by aldolase, and the two can be interconverted by triosephosphate isomerase. Glyceraldehyde can enter the glycolysis pathway through triokinase, and it can also be converted to glycerate and then 3-phosphoglycerate by glyceraldehyde dehydrogenase and glycerate kinase. DHAP and glycerol 3-phosphate can participate in the glycerol 3-P shuttle to regenerate NAD+ for glycolysis. The oxidation of Gl-3-P to 1,3-bisphosphoglycerate is catalyzed by Gl-3-P dehydrogenase, and this reaction requires NAD+. NADH can be oxidized through various reactions to regenerate NAD+ for glycolysis. Phosphoglycerate kinase catalyzes the transfer of a high-energy phosphate bond from 1,3-bisphosphoglycerate to ADP, generating ATP. Enolase dehydrates 2-phosphoglycerate to form phosphoenolpyruvate, another high-energy compound. Pyruvate kinase transfers the high-energy phosphate of phosphoenolpyruvate to ADP, generating ATP and pyruvate. Anaerobic glycolysis yields a net of two ATP per glucose molecule. Under aerobic conditions, NADH can be shuttled into mitochondria for ATP production, resulting in a total of 8 ATP molecules derived from cytoplasmic glucose oxidation. The complete aerobic oxidation of glucose can yield up to 38 ATP equivalents. The remaining energy in glucose is released as heat.
OUTLINE
Anaerobic glycolysis begins with the cleavage of fructose 1,6-bisphosphate (Frc-1,6-bisP) into dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (Gl-3-P) by aldolase.
DHAP and Gl-3-P can be interconverted by triosephosphate isomerase.
Fructose 1-phosphate (Frc-1-P) can also be split into glyceraldehyde and DHAP by aldolase.
Glyceraldehyde can enter the glycolysis pathway via triokinase, which phosphorylates it to glyceraldehyde 3-phosphate (Gl-3-P).
Glyceraldehyde can also be converted to glycerate by glyceraldehyde dehydrogenase, and then to 3-phosphoglycerate (3-PG) by glycerate kinase.
DHAP and glycerol 3-phosphate can participate in the "glycerol 3-P shuttle" to regenerate NAD+ in the mitochondria.
Glycolysis proceeds by oxidizing Gl-3-P to 1,3-bisphosphoglycerate (1,3-bisPG) via Gl-3-P dehydrogenase.
NADH generated in glycolysis can be oxidized by various reactions to regenerate NAD+.
Phosphoglycerate kinase transfers the high-energy phosphate bond from 1,3-bisPG to ADP, generating ATP.
Enolase dehydrates 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP), another high-energy compound.
Pyruvate kinase transfers the high-energy phosphate of PEP to ADP, generating ATP and pyruvate.
Anaerobic glycolysis yields a net of two ATP per glucose molecule.
Under aerobic conditions, NADH can enter the mitochondrial respiratory chain to generate ATP.
The complete aerobic oxidation of glucose can yield up to 38 ATP equivalents.
Approximately 42% of the energy from glucose is captured as ATP during aerobic combustion, with the remaining energy released as heat.
QUESTIONS
Qcard 1:
Question: What are the intermediate reactions in anaerobic glycolysis?
Answer: The intermediate reactions in anaerobic glycolysis involve the cleavage of fructose 1,6-bisphosphate (Frc-1,6-bisP) into dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (Gl-3-P).
Qcard 2:
Question: What enzyme catalyzes the conversion of Frc-1,6-bisP to Gl-3-P and DHAP?
Answer: Aldolase catalyzes the conversion of Frc-1,6-bisP to Gl-3-P and DHAP.
Qcard 3:
Question: What is the role of triosephosphate isomerase in anaerobic glycolysis?
Answer: Triosephosphate isomerase interconverts DHAP and Gl-3-P, with a strong favor towards Gl-3-P formation.
Qcard 4:
Question: How is glyceraldehyde 3-phosphate (Gl-3-P) formed in anaerobic glycolysis?
Answer: Glyceraldehyde can be phosphorylated to Gl-3-P by the enzyme triokinase.
Qcard 5:
Question: What is the first site of ATP production in the EMP?
Answer: The formation of 3-phosphoglycerate (3-PG) from 1,3-bisphosphoglycerate (1,3-bisPG) catalyzed by phosphoglycerate kinase is the first site of ATP production in the EMP.
Qcard 6:
Question: What is the role of enolase in anaerobic glycolysis?
Answer: Enolase catalyzes the dehydration of 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP), another high-energy compound.
Qcard 7:
Question: What enzyme catalyzes the conversion of PEP to pyruvate in anaerobic glycolysis?
Answer: Pyruvate kinase catalyzes the conversion of PEP to pyruvate, generating two moles of ATP per mole of glucose oxidized.
Qcard 8:
Question: How many ATP molecules are generated in anaerobic glycolysis from the conversion of one glucose molecule?
Answer: Anaerobic glycolysis generates a net yield of
Cleavage of Fructose 1,6-bisphosphate
Interconversion of DHAP and Gl-3-P
Entry of Glyceraldehyde into EMP
Glycerol 3-P Shuttle
Oxidation of Gl-3-P to 1,3-bisPG
Formation of 3-PG from 1,3-bisPG
Dehydration of 2-PG to PEP
Conversion of PEP to Pyruvate
Aldolase catalyzes the conversion of Frc-1,6-bisP to Gl-3-P and DHAP.
Triosephosphate isomerase interconverts DHAP and Gl-3-P.
Aldolase splits Frc-1-P into glyceraldehyde and DHAP.
Triokinase phosphorylates glyceraldehyde to Gl-3-P.
Glycerol 3-P dehydrogenase converts DHAP to glycerol 3-phosphate.
Glycerol 3-phosphate participates in the glycerol 3-P shuttle to regenerate NAD+.
Gl-3-P dehydrogenase oxidizes Gl-3-P to 1,3-bisPG, generating NADH.
Phosphoglycerate kinase transfers the high-energy phosphate from 1,3-bisPG to ADP, generating ATP.
Enolase catalyzes the dehydration of 2-PG to PEP.
Read and understand the overall process of anaerobic glycolysis.
Focus on the cleavage of fructose 1,6-bisphosphate (Frc-1,6-bisP) into dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (Gl-3-P) by aldolase (#8).
Study the interconversion of DHAP and Gl-3-P by triosephosphate isomerase (#9).
Learn about the formation of 1,3-bisphosphoglycerate (1,3-bisPG) from Gl-3-P (#15).
Review the conversion of fructose 1-phosphate (Frc-1-P) to glyceraldehyde and DHAP by aldolase (#10).
Understand the role of triokinase (#11) in phosphorylating glyceraldehyde to Gl-3-P.
Study the formation of glycerate from glyceraldehyde by glyceraldehyde dehydrogenase (#12).
Learn about the catalysis of 3-phosphoglycerate (3-PG) formation from glycerate by glycerate kinase (#13).
Focus on the role of dihydroxyacetone phosphate as a precursor to glycerol 3-phosphate and its catalysis by glycerol 3-P dehydrogenase (#14).
Understand the importance of NAD+ regeneration and the involvement of DHAP and glycerol 3-P in the "glycerol 3-P shuttle".
Study the oxidation of glyceraldehyde 3-phosphate to 1,3-bisPG by glyceraldehyde 3-P dehydrogenase (#15).
Review the transfer of the high-energy phosphate bond from 1,3-bisPG to ADP by phosphoglycerate kinase (#16) for ATP production.
Understand the role of diphosphoglyceromutase (#17) in the formation of 2,3-bisphosphoglycerate (2,3-bisPG) in erythrocytes.
Study the transfer of phosphate from position 3 of 3-PG to position 2 by phosphoglyceromutase (#19)
