清华大学生物化学课件糖酵解
合集下载
- 1、下载文档前请自行甄别文档内容的完整性，平台不提供额外的编辑、内容补充、找答案等附加服务。
- 2、"仅部分预览"的文档,不可在线预览部分如存在完整性等问题,可反馈申请退款(可完整预览的文档不适用该条件!)。
- 3、如文档侵犯您的权益，请联系客服反馈,我们会尽快为您处理(人工客服工作时间：9:00-18:30)。
• Is also a versatile precursor for carbon skeletons of almost all kinds of biomolecules.
Major pathways of glucose utilization
Glycolysis
• The first stage in the complete oxidation of glucose
Step 2
Aldose
Preparatory Phase Ketose
Reversible Reversible
Step 3 The commitment Preparatory Phase step
Irreversible exergonic
(PFK1)
Step 4 The “lysis” stePpreparatory Phase
• They also separated the yeast juice into two fractions: one heat-labile, nondialyzable zymase (enzymes) and the other heat-stable, dialyzable cozymase (metal ions, ATP, ADP, NAD+).
isomerization, aldol cleavage, dehydrogenation, group shift, and dehydration. • All the enzymes are found in the cytosol. • All intermediates are phosphorylated. • Only a small fraction (~5.2%) of the potential energy of the glucose molecule is released and much still remains in the final product of glycolysis, pyruvate.
Overview on glucose metabolism
• The major fuel of most organisms and occupies a central
position in metabolism (G'o= -2840 kJ/mol when
completely oxidized).
• Can be stored in polymer form (glycogen or starch) or be converted to fat for long term storage.
• Can also be oxidized to make NADPH and ribose 5phosphate via the pentose phosphate pathway.
2. The overall glycolytic pathway can be divided into two phases
• Preparatory phase: Glucose is converted into glyceraldehyde 3-phosphate, consuming ATP.
大家好
Glycolysis,thepent osephosphatepath wayandthecatabol
ismofglycogen
Glycolysis (糖酵解)
The process in which a molecule of glucose is degraded in a series of enzyme-catalyzed reactions to yield two molecules of pyruvate.
• In 1900s, Arthur Harden and William Young (Great Britain) found that Pi is needed for yeast juice to ferment glucose, a hexose diphosphate (fructose 1,6-bisphosphate) was isolated.
ቤተ መጻሕፍቲ ባይዱ
aldolase
P
Dihydroxyacetone phosp+haGtelyceraldehyde 3-phosphate
triose phosphate isomerase
Glyceraldehyde 3-phosphate (2)2Pi
glyceraldehyde 3-phosphate dehydrogenase
Payoff Phase
2,3-bisphosphoglycerate is both a coenzyme and an intermediate of the reaction
Step 9
Payoff Phase
Reversible
Step 10
Substrate-level phosphorylation for ATP generation
• An universal central pathway of glucose metabolism
• The chemistry of the reaction sequence completely conserved during evolution
• The first metabolic pathway to be elucidated and probably the best understood
• The accepted view that fermentation is inextricably tied to living cells (i.e., the vitalistic dogma) was shaken and Biochemistry was born: Metabolism became chemistry!
Payoff Phase
Spontaneous
Isomerization
Dehydrogenation
Group transfer
Group shift Dehydration Group transfer
Four molecules of ATP and two molecules of NADH
• 1910s-1930s, Gustav Embden and Otto Meyerhof (Germany), studied muscle and its extracts:
– Reconstructed all the transformation steps from glycogen to lactic acid in vitro; revealed that many reactions of lactic acid (muscle) and alcohol (yeast) fermentations were the same!
1. The Development of Biochemistry and the Delineation of Glycolysis Went Hand by Hand
• In 1897, accidental observation by Eduard Buchner: sucrose (as a preservative) was rapidly fermented into alcohol by cell-free yeast extract.
Ketose
Aldose
Step 5
Preparatory Phase
Reversible
Ketose
Ketose
Aldose
Group transfer Isomerization Group transfer
Aldol cleavage
Isomerization
Two molecules of ATP are consumed
Payoff Phase Step 6 Oxidation and phosphorylation reaction
Acyl phosphate
Step 7
Substrate-level phosphorylation for ATP generation
Payoff Phase
Step 8
• Payoff phase: Glyceraldehyde 3-phosphate is oxidized to generate pyruvate, generating ATP and NADH.
Group transfer Isomerization Group transfer
Aldol cleavage
Isomerization
Isomerization Dehydrogenation Group transfer
Group shift Dehydration Group transfer
Step 1
Preparatory Phase
IrIrreerxveeevrregsroisbnilbieclein cells MgATP2-, not ATP4-, is the actual substrate
G'o = -85 kJ/mol
Glucose
ATP
hexokinase
Glucose 6-phosphate ADP
phosphohexose isomerase
Fructose 6-phosphate
ATP
phosphofructokinase-1
Fructose 1,6-bisphosphate AD
2NAD
+
2NAD
1,3-Bisphosphoglycerate (2) H
+ H+
phosphoglycerate
2ADP
kinas3e-Phosphoglycerate (2)
2AT P
phosphoglycerate mutase
2-Phosphoglycerate (2)
enolase
Phosphoenolpyruvate (2)
The chemical logic of the glycolytic pathway
• A net gain of two ATP, two NADH, two molecules of pyruvate are resulted when a glucose molecule is oxidized via the glycolysis pathway: Glucose + 2 ADP + 2Pi + 2NAD+ 2 pyruvate + 2ATP + 2H2O + 2NADH + 2H+
– Discovered that lactic acid is reconverted to carbohydrate in the presence of O2 (gluconeogenesis); observed that some phosphorylated compounds are energy-rich.
• The whole pathway of glycolysis (from glucose to pyruvate) was elucidated by the 1940s.
Basic facts about glycolysis
• Ten steps of reactions are involved in the pathway. • Six types of reactions occur: group transfer,
2ADP
pyruvate kinase
Pyruvate (2)
2AT P
Importance of phosphorylated intermediates
• Negatively charged, can’t diffuse out of the cell, therefore, no energy is needed to retain them in the cell
• Energy conserved in the phosphorylated compounds
Major pathways of glucose utilization
Glycolysis
• The first stage in the complete oxidation of glucose
Step 2
Aldose
Preparatory Phase Ketose
Reversible Reversible
Step 3 The commitment Preparatory Phase step
Irreversible exergonic
(PFK1)
Step 4 The “lysis” stePpreparatory Phase
• They also separated the yeast juice into two fractions: one heat-labile, nondialyzable zymase (enzymes) and the other heat-stable, dialyzable cozymase (metal ions, ATP, ADP, NAD+).
isomerization, aldol cleavage, dehydrogenation, group shift, and dehydration. • All the enzymes are found in the cytosol. • All intermediates are phosphorylated. • Only a small fraction (~5.2%) of the potential energy of the glucose molecule is released and much still remains in the final product of glycolysis, pyruvate.
Overview on glucose metabolism
• The major fuel of most organisms and occupies a central
position in metabolism (G'o= -2840 kJ/mol when
completely oxidized).
• Can be stored in polymer form (glycogen or starch) or be converted to fat for long term storage.
• Can also be oxidized to make NADPH and ribose 5phosphate via the pentose phosphate pathway.
2. The overall glycolytic pathway can be divided into two phases
• Preparatory phase: Glucose is converted into glyceraldehyde 3-phosphate, consuming ATP.
大家好
Glycolysis,thepent osephosphatepath wayandthecatabol
ismofglycogen
Glycolysis (糖酵解)
The process in which a molecule of glucose is degraded in a series of enzyme-catalyzed reactions to yield two molecules of pyruvate.
• In 1900s, Arthur Harden and William Young (Great Britain) found that Pi is needed for yeast juice to ferment glucose, a hexose diphosphate (fructose 1,6-bisphosphate) was isolated.
ቤተ መጻሕፍቲ ባይዱ
aldolase
P
Dihydroxyacetone phosp+haGtelyceraldehyde 3-phosphate
triose phosphate isomerase
Glyceraldehyde 3-phosphate (2)2Pi
glyceraldehyde 3-phosphate dehydrogenase
Payoff Phase
2,3-bisphosphoglycerate is both a coenzyme and an intermediate of the reaction
Step 9
Payoff Phase
Reversible
Step 10
Substrate-level phosphorylation for ATP generation
• An universal central pathway of glucose metabolism
• The chemistry of the reaction sequence completely conserved during evolution
• The first metabolic pathway to be elucidated and probably the best understood
• The accepted view that fermentation is inextricably tied to living cells (i.e., the vitalistic dogma) was shaken and Biochemistry was born: Metabolism became chemistry!
Payoff Phase
Spontaneous
Isomerization
Dehydrogenation
Group transfer
Group shift Dehydration Group transfer
Four molecules of ATP and two molecules of NADH
• 1910s-1930s, Gustav Embden and Otto Meyerhof (Germany), studied muscle and its extracts:
– Reconstructed all the transformation steps from glycogen to lactic acid in vitro; revealed that many reactions of lactic acid (muscle) and alcohol (yeast) fermentations were the same!
1. The Development of Biochemistry and the Delineation of Glycolysis Went Hand by Hand
• In 1897, accidental observation by Eduard Buchner: sucrose (as a preservative) was rapidly fermented into alcohol by cell-free yeast extract.
Ketose
Aldose
Step 5
Preparatory Phase
Reversible
Ketose
Ketose
Aldose
Group transfer Isomerization Group transfer
Aldol cleavage
Isomerization
Two molecules of ATP are consumed
Payoff Phase Step 6 Oxidation and phosphorylation reaction
Acyl phosphate
Step 7
Substrate-level phosphorylation for ATP generation
Payoff Phase
Step 8
• Payoff phase: Glyceraldehyde 3-phosphate is oxidized to generate pyruvate, generating ATP and NADH.
Group transfer Isomerization Group transfer
Aldol cleavage
Isomerization
Isomerization Dehydrogenation Group transfer
Group shift Dehydration Group transfer
Step 1
Preparatory Phase
IrIrreerxveeevrregsroisbnilbieclein cells MgATP2-, not ATP4-, is the actual substrate
G'o = -85 kJ/mol
Glucose
ATP
hexokinase
Glucose 6-phosphate ADP
phosphohexose isomerase
Fructose 6-phosphate
ATP
phosphofructokinase-1
Fructose 1,6-bisphosphate AD
2NAD
+
2NAD
1,3-Bisphosphoglycerate (2) H
+ H+
phosphoglycerate
2ADP
kinas3e-Phosphoglycerate (2)
2AT P
phosphoglycerate mutase
2-Phosphoglycerate (2)
enolase
Phosphoenolpyruvate (2)
The chemical logic of the glycolytic pathway
• A net gain of two ATP, two NADH, two molecules of pyruvate are resulted when a glucose molecule is oxidized via the glycolysis pathway: Glucose + 2 ADP + 2Pi + 2NAD+ 2 pyruvate + 2ATP + 2H2O + 2NADH + 2H+
– Discovered that lactic acid is reconverted to carbohydrate in the presence of O2 (gluconeogenesis); observed that some phosphorylated compounds are energy-rich.
• The whole pathway of glycolysis (from glucose to pyruvate) was elucidated by the 1940s.
Basic facts about glycolysis
• Ten steps of reactions are involved in the pathway. • Six types of reactions occur: group transfer,
2ADP
pyruvate kinase
Pyruvate (2)
2AT P
Importance of phosphorylated intermediates
• Negatively charged, can’t diffuse out of the cell, therefore, no energy is needed to retain them in the cell
• Energy conserved in the phosphorylated compounds