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-탄수화물 대사의 주요회로(그림8.1)
8.1 해당작용
-혐기성생물: 해당과정 이용 (EMP 회로로도 불림)
-호기성호흡: 피르브산을 CO2, H2O로 산화
(1)해당경로의 반응(그림8.2): 양반응회로 (이화와 동화)
1. 글루코오스-6-인산의 합성(그림)
2. 글루코오스-6-인산의 프룩토오스-6-인산으로의 전환
3. 프룩토오스-6-인산의 인산화; 포스포프룩토키나제-1은 주요 조절효소
-다른자리입체성 활성제(AMP), 억제제(ATP, 시트르산)
4. 프룩토오스-1,6-이인산의 절단:알돌절단
5. 글리세르알데히드-3-인산과 디히드록시아세톤인산의 상호전환
6. 글리세르알데히드-3-인산의 산화
- 글리세르알데히드-3-인산 탈수소효소(GAPDH)는 기질과 티오에스테르결합을
하면서 수소화이온을 활성자리에 있는 NAD+에 전이함(그림8.3)
7. 인산기전이
-기질수준인산화; 높은 인산기 전이전위를 갖는 기질에서 ATP합성
Chapter 8
Carbohydrate Metabolism
Overview
Metabolism and Jet Engines
 Section 8.1: Glycolysis
 Section 8.2: Gluconeogenesis
 Section 8.3: The Pentose Phosphate Pathway
 Section 8.4: Metabolism of Other Important Sugars
 Section 8.5: Glycogen Metabolism
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Chapter 8: Overview
Figure 8.1 Major Pathways in
Carbohydrate Metabolism
Energy transforming pathways of carbohydrate
metabolism include glycolysis, glycogenesis,
glycogenolysis, gluconeogenesis, and pentose phosphate
pathway
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.1: Glycolysis
Figure 8.1 Major Pathways in
Carbohydrate Metabolism
Glycolysis (anaerobic process) occurs in almost
every living cell
Ancient process central to all life
Splits glucose into two three-carbon pyruvate units
Catabolic process that captures some energy as
2 ATP and 2 NADH
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.1: Glycolysis
Glycolysis is an anaerobic process
Two stages (stage 1 and 2): energy investment and
energy producing
Glycolytic Pathway: D-Glucose + 2 ADP + 2 Pi + 2
NAD+  2 pyruvate + 2 ATP + 2 NADH + 2 H+ + 2
H 2O
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.1: Glycolysis
Figure 8.2 Glycolytic Pathway
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.1: Glycolysis
Figure 8.2 Glycolytic
Pathway
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.1: Glycolysis
Reactions of the Glycolytic
Pathway
1. Synthesis of glucose-6phosphate
Phosphorylation of
glucose (kinase) prevents
transport out of the cell
and increases reactivity
2. Conversion of glucose-6phosphate to fructose-6phosphate
Figure 8.2a Glycolytic Pathway
Conversion of aldose to
ketose
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.1: Glycolysis
Reactions of the Glycolytic
Pathway Continued
3. Phosphorylation of
fructose-6-phosphate
This step is irreversible
due to a large decrease in
free energy and commits
the molecule to glycolysis
4. Cleavage of fructose-1,6bisphosphate
Figure 8.2a Glycolytic Pathway
Aldol cleavage giving an
aldose and ketose product
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.1: Glycolysis
Reactions of the Glycolytic
Pathway Continued
5. Interconversion of
glyceraldehyde-3phosphate and
dihydroxyacetone
phosphate
Conversion of aldose to
ketose enables all carbons
to continue through
glycolysis
Figure 8.2a Glycolytic Pathway
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.1: Glycolysis
Reactions of the Glycolytic
Pathway Continued
In Step 2 (reactions 6-10), each
reaction occurs in duplicate
6. Oxidation of glyceraldehyde3-phosphate
Creates high-energy
phosphoanhydride bond for
ATP formation and NADH
7. Phosphoryl group transfer
Production of ATP via
substrate-level
phosphorylation
Figure 8.2b Glycolytic Pathway (Stage 2)
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
8. 글리세린산-3-인산과 글리세린산-2-인산의 상호작용: 전환반응
9. 글리세린산-2-인산의 탈수반응(PEP생성)
-엔올라제
-토토머라고도 불리는 케토와 엔올형의 상호전환을 토토머화라함
-해당과정 10개 반응도식(그림8.4)
10. 피루브산의 합성
(2)피르브산의 운명
-구연산회로 (탈카복실화 후에)
-전자전달계; 산화환원반응, 양성자구배
-발효(그림8.5): 젖산(그림8.6)-호모젖산발효생물,
에탄올-헤테로젖산발효생물(), 탈카복실화, 부탄올
-포도주제조: 에틸아세트산, 아밀알코올, 티라민은 숙취유발
-맥주양조
Section 8.1: Glycolysis
Reactions of the Glycolytic
Pathway Continued
8. Interconversion of
3-phosphoglycerate and
2-phosphoglycerate
First step in formation of
phosphoenolpyruvate (PEP)
9. Dehydration of
2-phosphoglycerate
Production of PEP, which has
a high phosphoryl group
transfer potential
(tautomerization), locks it into
the highest energy form
Figure 8.2b Glycolytic Pathway (Stage 2)
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.1: Glycolysis
Reactions of the Glycolytic
Pathway Continued
10. Synthesis of pyruvate
Formation of pyruvate and ATP
Produces a net of 2 ATP, 2
NADH, and 2 pyruvate
Figure 8.2b Glycolytic Pathway (Stage 2)
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.1: Glycolysis
Figure 8.3Glyceraldehyde-3-Phosphate
Dehydrogenase Reaction
Oxidation of glyceraldehyde-3-phosphate (G-3-P) is a
2-step process (reaction 6)
G-3-P undergoes oxidation and phosphorylation
G-3-P interacts with the sulfhydryl group in the
enzyme’s active site
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.1: Glycolysis
Figure 8.3 Glyceraldehyde-3-Phosphate
Dehydrogenase Reaction
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.1: Glycolysis
Oxidation of glyceraldehyde-3-phosphate (G-3-P) is
a complex process (reaction 6)
Substrate oxidized after interaction with sulfhydryl
Bound NADH exchanged for NAD+
Enzyme displaced by addition of inorganic
phosphate
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.1: Glycolysis
Figure 8.5 The Fates of Pyruvate
The Fates of Pyruvate
Pyruvate is an energy-rich molecule
Under aerobic conditions, pyruvate is converted to
acetyl-CoA for use in the citric acid cycle and electron
transport chain
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.1: Glycolysis
The Fates of Pyruvate
Continued
Under anaerobic conditions
pyruvate can undergo
fermentation: alcoholic or
homolactic
Regenerates NAD+ so
glycolysis can continue
Figure 8.6 Recycling NADH
during Anaerobic Glycolysis
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
(3)해당과정의 에너지론
-각 개별 반응의 표준자유에너지변화, 회로의 효율성(그림8.7)
-가역적, 비가역적, 글루코오스신생
(4)해당작용의 조절
*육탄당 인산화효소
*다른자리입체성조절
-PFK-1과 피루브산키나아제 효소의 다른자리 입체성조절(그림8.8, 표8.1)
*호르몬조절
*AMPK: A 대사의 주요 전환점
8.2 포도당 신생합성
-간에서 일어남, 혈당량조절; 대사산독증 및 기아시 신장에서
- 전구물질: 젖산, 피루브산, 글리세롤, α-케토산 등
(1) 포도당 신생합성 반응
-3개의 해당과정은 비가역적, 신생반응에서는 다른 효소로 극복
-그림8.9, 신생회로와 해당과정의 상관관계
1. 포스포엔올피루브산의 합성
-피루브산 카르복실화효소(미토콘드리아의)와
-PEP 카르복시키나아제 ; OAA를 말산셔틀(말산탈수소효소사용)을 사용하여
세포질로 전이 (284p)
Section 8.1: Glycolysis
Figure 8.7 Free Energy Changes during Glycolysis in Red Blood Cells
Energetics of Glycolysis
In red blood cells, only three reactions have
significantly negative DG values
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.1: Glycolysis
Regulation of Glycolysis
The rate of the glycolytic pathway in a cell is
controlled by the allosteric enzymes:
Hexokinases I, II, and III
PFK-1
Pyruvate kinase
Allosteric enzymes are sensitive indicators of a cell’s
metabolic state regulated locally by effector molecules
The peptide hormones glucagon and insulin also regulate
glycolysis
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.1: Glycolysis
Regulation of Glycolysis Continued
High AMP concentrations activate pyruvate kinase
Fructose-2,6-bisphosphate, produced via hormoneinduced covalent modification of PFK-2, activates
PFK-1
Accumulation of fructose-1,6-bisphosphate activates
PFK-1 providing a feed-forward mechanism
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.1: Glycolysis
Figure 8.8 Fructose-2,6-Bisphosphate Level Regulation
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.2: Gluconeogenesis
Gluconeogenesis is the formation of new glucose
molecules from precursors in the liver
Precursor molecules include lactate, pyruvate, and
a-keto acids
Gluconeogenesis Reactions
Reverse of glycolysis except the three irreversible
reactions
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.2: Gluconeogenesis
Figure 8.9 Carbohydrate Metabolism: Gluconeogenesis and Glycolysis
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.2: Gluconeogenesis
Figure 8.9 Carbohydrate Metabolism: Gluconeogenesis and Glycolysis
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
2. 프룩토오스-1,6-이인산의 프룩토오스-6-인산으로의 전환
-프룩토오스-1,6-이인산가수분해효소로 우회
3. 글루코오스-6-인산으로부터 글루코오스 합성
-간, 신장에만 글루코오스-6-인산 가수분해효소존재
-신생과 해당반응이 협동적으로 조절됨
(2)포도당 신생합성 기질
-코리회로에서 젖산은 운동 중 골격근육에 의해 방출된다(그림8.10)
-운동하는 근육이 다량의 피루브산을 만들 때 일부는 아미노산 전이반응에 의해
알라닌으로 전환됨;글루코오스-알라닌회로(그림8.11)
(3)포도당 신생합성 조절
-인슐린, 글루카곤 (그림8.12)
(*글루코오스를 이용하는 뇌
-PET 스캔(그림))
Section 8.2: Gluconeogenesis
Gluconeogenesis Reactions Continued
Three bypass reactions:
1. Synthesis of phosphoenolpyruvate (PEP) via the
enzymes pyruvate carboxylase and pyruvate
carboxykinase
2. Conversion of fructose-1,6-bisphosphate to fructose6-phosphate via the enzyme fructose-1,6bisphosphatase
3. Formation of glucose from glucose-6-phosphate via
the liver and kidney-specific enzyme glucose-6phosphatase
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.2: Gluconeogenesis
Gluconeogenesis Substrates
Three of the most important
substrates for gluconeogenesis
are:
1. Lactate—released by
skeletal muscle from the Cori
cycle
After transfer to the liver
lactate is converted to
pyruvate, then to glucose
2. Glycerol—a product of fat
metabolism
Figure 8.10 Cori Cycle
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.2: Gluconeogenesis
Figure 8.11 The Glucose Alanine Cycle
Gluconeogenesis Substrates Continued
3. Alanine—generated from pyruvate in exercising
muscle
Alanine is converted to pyruvate and then glucose
in the liver
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.2: Gluconeogenesis
Gluconeogenesis
Regulation
Substrate availability
Hormones (e.g., cortisol
and insulin)
Figure 8.12 Allosteric Regulation of
Glycolysis and Gluconeogenesis
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.2: Gluconeogenesis
Gluconeogenesis
Regulation Continued
Allosteric enzymes
(pyruvate carboxylase,
pyruvate
carboxykinase,
fructose-1,6bisphosphatase, and
glucose-6-phosphatase)
+
Figure 8.12 Allosteric Regulation of
Glycolysis and Gluconeogenesis
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
8.3 오탄당인산 회로
-ATP재생은 없으며, NADPH와 리보오스-5-인산가 주 생성물
-산화적(그림 8.13a) 및 비산화적단계 (그림 8.13b)
-지질합성, 항산화작용 등 환원과정에 필요한 상당량의 NADPH합성이 일어남
- NADPH는 강력한 항산화제
- 그림8.13b: 삼탄당, 오탄당, 육탄당의 상호전환
- 오탄당이 생합성반응에 사용되지 않을 때 비산화적단계의 대사물질은 해당과정의
중간물질로 전환되어 분해됨(그림8.14): 육탄당일인산회로도 명명
8.4 다른 중요한 당의 대사(그림8.15)
(1) 과당 대사
-두가지 경로로 해당과정에 들어감
((2)갈락토오스대사
-갈락토오스-갈락토오스1인산; 갈락토오스1인산-UDP갈락토오스;
UDP갈락토오스- UDP글루코오스; 글리코겐합성 혹은 글루코오스1인산
(3)만노오스대사: 프룩토오스6인산으로 전환)
Section 8.3: Pentose Phosphate Pathway
Glucose-6-phosphate
dehydrogenase
Gluconolactonase
Pentose Phosphate
Pathway
Alternate glucose
metabolic pathway
Products are NADPH
and ribose-5phosphate
Two phases:
oxidative and
nonoxidative
Figure 8.13a The Pentose Phosphate Pathway (oxidative)
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.3: Pentose Phosphate Pathway
6-phosphogluconate
dehydrogenase
Pentose Phosphate
Pathway: Oxidative
Three reactions
Results in ribulose5-phosphate and two
NADPH
NADPH is a
reducing agent used
in anabolic processes
Figure 8.13a The Pentose Phosphate Pathway (oxidative)
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.3: Pentose Phosphate Pathway
Pentose Phosphate
Pathway: Nonoxidative
Produces important
intermediates for nucleotide
biosynthesis and glycolysis
Ribose-5-phosphate
Glyceraldehyde-3phosphate
Fructose-6-phosphate
Figure 8.13b The Pentose Phosphate
Pathway (nonoxidative)
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.3: Pentose Phosphate Pathway
Pentose Phosphate
Pathway
If the cell requires
more NADPH than
ribose molecules,
products of the
nonoxidative phase
can be shuttled into
glycolysis
Figure 8.14 Carbohydrate
Metabolism: Glycolysis
and the Phosphate
Pathway
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.4: Metabolism of Other Important Sugars
Figure 8.15 Carbohydrate Metabolism:
Galactose Metabolism
Fructose, mannose, and galactose are also important
sugars for vertebrates
Most common sugars found in oligosaccharides
besides glucose
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.4: Metabolism of Other Important Sugars
Fructose Metabolism
Second to glucose in the human diet
Can enter the glycolytic pathway in two ways:
Through the liver (multi-enzymatic process)
Muscle and adipose tissue (hexokinase)
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.4: Metabolism of Other Important Sugars
Figure 8.15 Carbohydrate Metabolism:
Other Important Sugars
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
8.5 글리코겐대사
-분해 및 합성은 인슐린, 글루카곤, 에피네프린에 의해 조절
(1)글리코겐합성
1. 글루코오스-1-인산의 합성
2. UDP-글루코오스의 합성; 글루코오스보다 반응성이 높다.
3. UDP-글루코오스로부터 글리코겐 합성
-두 가지효소가 필요: 글리코겐합성효소(그림8.16a),
α(1.6)결합분지효소[아밀로-α(1,4→1.6)-글루코실 전이효소](그림8.16b)
(2)글리코겐분해
-두 반응을 필요: 글리코겐의 비환원말단으로부터
글루코오스제거(덱스트린형성까지 진행)(그림8.17), 글리코겐의 분지점에서
α(1.6)글리코시드 결합의 가수분해, 자유글루코오스형성(그림8.18)
-요약(그림8.19)
(3)글리코겐의 대사조절
-호르몬에 의해(인슐린, 글루카곤, 에피네프린)
-아데닐산 시클라아제, cAMP(2차 전령), 인산화다단계반응
-그림8.20
Section 8.5: Glycogen Metabolism
Glycogenesis
Synthesis of glycogen, the storage form of glucose,
occurs after a meal
Requires a set of three reactions (1 and 2 are
preparatory and 3 is for chain elongation):
1. Synthesis of glucose-1-phosphate (G1P) from glucose6-phosphate by phosphoglucomutase
2. Synthesis of UDP-glucose from G1P by UDP-glucose
phosphorylase
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.5: Glycogen Metabolism
Figure 8.16a Glycogen
Synthesis
Glycogen
synthase
Glycogenesis Continued
3. Synthesis of Glycogen from UDP-glucose requires two
enzymes:
 Glycogen synthase to grow the chain
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.5: Glycogen Metabolism
Glycogenesis
Continued
Branching enzyme
amylo-a(1,41,6)glucosyl transferase
creates a(1,6)
linkages for
branches
Branching
enzyme
a(1,6) Glycosidic Linkage is formed
Figure 8.16b Glycogen Synthesis
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.5: Glycogen Metabolism
Glycogenolysis
Glycogen degradation requires two reactions:
1. Removal of glucose from nonreducing ends (glycogen
phosphorylase) within four glucose of a branch point
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.5: Glycogen Metabolism
Figure 8.17 Glycogen
Degradation
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.5: Glycogen Metabolism
Glycogenolysis Cont.
Glycogen degradation
requires two reactions:
2. Hydrolysis of the
a(1,6) glycosidic
bonds at branch
points by amyloa(1,6)-glucosidase
(debranching
enzyme)
Amylo-a(1,6)-glucosidase
Amylo-a(1,6)-glucosidase
Figure 8.19 Glycogen Degradation
via Debranching Enzyme
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.5: Glycogen Metabolism
Amylo-a(1,6)-glucosidase
Figure 8.18 Glycogen Degradation via Debranching Enzyme
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.5: Glycogen Metabolism
Regulation of
Glycogen Metabolism
Figure 8.20 Major Factors Affecting
Glycogen Metabolism
Carefully regulated
to maintain
consistent energy
levels
Regulation involves
insulin, glucagon,
epinephrine, and
allosteric effectors
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Section 8.5: Glycogen Metabolism
Glucagon activates
glycogenolysis
Insulin inhibits
glycogenolysis and
activates glycogenesis
Epinephrine release
activates
glycogenolysis and
inhibits glycogenesis
Figure 8.20 Major Factors Affecting
Glycogen Metabolism
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Biochemistry in Perspective
Saccharomyces cerevisiae and the Crabtree effect
S. cerevisiae is the only yeast that can produce
ethanol and CO2 in such large quantities
S. cerevisiae ferments carbohydrates efficiently and
dominates its environment due to the Crabtree effect
The Crabtree Effect
Unlike most fermenting organisms S. cerevisiae can
also ferment sugar in the presence of O2
As glucose and/or fructose levels rise pyruvate is
diverted away from the citric acid cycle into ethanol
synthesis
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Biochemistry in Perspective
The phenomenon, in which glucose represses aerobic
metabolism, is the Crabtree effect
Rapid production of ethanol has the effect of
eliminating microbial competitors
Once glucose levels are depleted and O2 is available
the yeast reabsorbs the ethanol and converts it to
acetaldehyde for use as an energy source
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press
Biochemistry in Perspective
Figure 8A Ethanol Metabolism in S.
cerevisiae
From McKee and McKee, Biochemistry, International Fifth Edition, © 2012 by Oxford University Press