Title: Chapter 8~9 Carbohydrate Metabolism
1 Chapter 89 Carbohydrate Metabolism
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4outline
- Background
- Glycolysis (Anaerobic Degradation)
- Aerobic oxidation of glucose
- The Pentose Phosphate Pathway
- Glycogen Formation and Degradation
- Gluconeogenesis
5Background
- Metabolism (Greek for change)
- all the chemical and physical
processes that take place in the body - Synthesis (anabolism)
- A Glucose Glycogen
- A FA Glycerol TG
- A Amino Acids Protein
Macromolecules
A Requires Energy
A Energy is released
Breakdown (catabolism) A
Glycogen Glucose A TG Fatty
Acids Glycerol A Protein
Amino Acids
Small molecules
6What are Carbohydrates?
- Carbohydrates are aldehyde or ketone compounds
with multiple hydroxyl groups - Empirical formula (CH2O)n, literally a carbon
hydrate - CH2O make up 3 of the bodys organic matter
7Functions of CH2O
- Energy Source(66.8 kJ/1g carbohydrate)
- Structural elements
- Component of nucleic acids
- Conversion to lipids and non-essential amino
acids - .
8Categories of Carbohydrates
- Monosaccharides (Single sugar units) the
smallest carbohydrates ,serve as fuel and carbon
sources - Disaccharides (formed from 2 monosaccharides
joined by a glycoside linkage) - Polysaccharides many monosaccharide units
(starch, cellulose)
9Monosaccharides
- Glucose (C6H12O6) ???
- -found in fruits, vegetables, honey
- -blood sugar
- -used for energy
- Fructose ??
- - Found in fruits, honey, corn syrup
- -fruit sugar
- Galactose ???
- - Found as part of lactose in milk
Glucose (C6H12O6)
??
??
10Disaccharides
- Sucrose glucose fructose (brown sugar25 of
sugar intake) ?? - Maltose glucose glucose (honey) ???
Natural Sweetness - Lactose glucose galactose (milk sugar least
sweet) ??
??gt??gt???gt???gt???
Sucrose
Maltose
11Polysaccharides
?? a-1,6-??? ?? a-1,4-???
starch
12Section 1 Digestion of carbohydrates
Starch
Pancreatic amylase
13BLOOD
Brush Border of the Mucosal Epithelium
stomach
Mouth
Starch
maltose
1
a-mylase
glucose
Glycogen
sucrose
2
fructose
lactose
3
galactose
galactose
glucose
Monosaccharides
fructose
no significant digestive enzymes present
Responsible for most of carbohydrate digestion
limited breakdown of starch and glycogen occurs
???? ??
14 Na dependent glucose Absorption and
transporter, GLT
facilitated diffusion
GLT
GLT
Nadependent co-transport
Intestinal Epithelial cell
15Family of glucose transporters
Name Tissue location Km
Comments
GLUT1 All mammalian tissues 1mmol/L
Basal glucose uptake GLUT2 Liver
and pancreatic 1520mmol/L In the
pancreas,plays a role ?
cells
in regulation of insulin
In the liver, removes
excess
glucose from the blood GLUT3 All mammalian
tissues 1mmol/L Basal glucose
uptake GLUT4 Muscle and fat cells
5mmol/L Amount in muscle plasma
membrane
increases with
endurance training GLUT5 Small
intestine -
Primarily a fructose transporter
16Not digested Dietary Fiber
- Water insoluble fibers
- - Cellulose, hemicellulose , pectins ??
- Water soluble fiber
- - beans, rice, carrots, fruits
- - Obesity, diabetes, cancer
- Recommended intake of fiber
- 20-35 g/day insolublesoluble 31
17Overview of carbohydrate metabolism
Glycogen
Glycogenesis
Glycogenolysis
UDPG
4
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G1P
glucose
G6P
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Anaerobic degradation (glycolysis)
Pyruvate
6
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acetyl CoA
1
Aerobic oxidation
2
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18 Section 2 Glycolysis (Anaerobic Degradation)
- Glycolysis is derived from Greek words glycos
(sugar, sweet) and lysis (dissolution) - The glycolytic pathway (Glucose to pyruvate) was
elucidated by 1940, largely through the
pioneering contributions of Gustav Embden. so
glycolysis is also known as the Embden-Meyerhof
pathway
19Glycolysis ???
- For glycolysis, the overall goal is to break the
glucose molecule into smaller, more oxidized
pieces - 11 steps metabolic pathway to convert 6 carbon
glucose into 2 molecules of 3 carbon lactate
??and two molecules ATP (and NADH ) - Occurs in cytoplasm
- glycolysis has two stages
- 1. glycolytic pathway (Glucose to pyruvate)
,including two phases - 2.Fermentation phase ?? (pyruvate to lactate)
- Anaerobic
- Does not REQUIRE oxygen
- Occurs whether oxygen is available or not
20 glycolytic pathway breakdown of glucose to
yield energy and pyruvate
break C3-C4 bond
breakage of C3-C4 bond
21glycolytic pathway has two phases
A. Energy investment phase (Reactions, 1-5)
Glucose(6C) is first phophorylated (thus
activated) and then cleaved to produce two
glyceraldehyde-3-phosphate(3C) intermediates. 2
ATPs are invested (the preparatory phase) B.
Energy payoff phase (Reactions 6-10) two
glyceraldehyde 3-phosphate intermediates are
oxidized, generating to two pyruvate plus four
ATP molecules
22Energy investment phase
isomerase
Step 1. Hexokinase (1 ATP utilization)
Step 2. Phosphoglucose Isomerase (PGI)
Step 3. Phosphofructokinase -1 (PFK-1) (2 ATP
utilization)
23energy investment phase
dihydroxyacetone phosphate
4. Aldolase
24energy investment phase
dihydroxyacetone phosphate
Glyceraldehyde 3-PO4
TPI
isomerase
The isomerization of an aldose to a ketose
5. Triose Phosphate Isomerase (TIM or TPI )
25energy investment phase
ATP
Hexokinase
ADP
Glucose 6-phosphate
Phosphogluco- isomerase
Uses 2 ATP
Fructose 6-phosphate
ATP
Phosphofructokinase
ADP
Fructose 1.6-bisphosphate
Aldolase
Glyceraldehyde 3-phosphate
Dihydroxyacetone phosphate
Triose phosphate isomerase
26Energy payoff phase
(Reactions, 6-10)
Glyceraldehyde-3-PO4 dehydrogenase
Phosphoglycerate kinase
Where ?
27Energy payoff phase
High energy
Low energy
28Glyceraldehyde 3-phosphate
Glyceraldehyde
3-phosphate
dehydrogenase
1,3-Bisphosphoglycerate
ADP
Phosphoglycerate kinase
ATP
3-Phosphoglycerate
Phosphoglyceromutase
2-Phosphoglycerate
Enolase
H2O
Phosphoenolpyruvate
ADP
Pyruvate kinase
ATP
energy payoff phase
29Energy payoff phase
Energy investment phase
30Summary of Energy Relationships for glycolytic
pathway
- Input 2 ATP
- 1. glucose ATP ? glucose-6-P
- 2. fructose-6-P ATP ? fructose 1,6
bisphosphate - Output 4 ATP 2 NADH
- 1. 2 glyceraldehyde-3-P 2 Pi 2 NAD?
- 2 (1,3
bisphosphoglycerate) 2 NADH - 2. 2 (1,3 bisphosphoglycerate) 2 ADP?
-
2 (3-P-glycerate) 2 ATP - 3. 2 PEP 2 ADP ? 2 pyruvate 2 ATP
- Net 2 ATP and 2 NADH
31Fate of Pyruvate
- Two anerobic pathways (Low O2 )
- - to lactate via lactate dehydrogenase in
muscle - - to ethanol (fermentation) via ethanol
dehydrogenase - Aerobic pathway through citric acid cycle and
respiration Enough O2,this pathway yields far
more energy - NADH O2 ? NAD energy
- Pyruvate O2 ? 3CO2 energy
Oxygen availability determines fate of Pyruvate
32The anaerobic fate of Pyruvate ( Reaction 11 of
glycolysis )
From?
- Hydrogen at C4 of NADH is transferred to the
pyruvate
uses up all the NADH (reducing equivalents)
produced in glycolysis
33Energy Yield From Glycolysis
Overall process of anaerobic glycolysis in muscle
can be represented
The lactate, the end product, is exported from
the muscle cell and carried by the blood to the
liver, where it is reconverted to glucose
- Glucose ---------6 CO2 -2840 kJ/mol
- 2 ATPs produced 61 kJ/mol glucose
- Energy yield 61/2840 2
- in all high investment, low output
34Summary of Glycolysis
6c?? 6c?3c ??? 3c-3c ??? 3c-3c
- 11 steps Location cytosol
- Original material glucose (C6H12O6)
- End product lactate
- - Twice substrate level phosphorylations
- - Net of 2 ATP
- d. Key enzymes Hexokinase (HK) energy
investment phase - Phosphofructokinase 1 (PFK-1)
energy investment phase - Pyruvate kinase (PK) energy payoff
phase - e. Once dehydrogenation oxidation
- Once hydrogenation reduction
- No oxygen is required
35The regulation of glycolysis
Hormone regulation Covalent regulation Allosteric
regulation
ATP
Glucagon
AMP
Adenylate cyclase
Citrate
cAMP
ADP
Glucose
ATP
Glucose 6-phosphate
ATP
F-6-P
F-2,6-BP
Phosphoprotein Phosphatase
PKA
ADP
Pi
glycolysis
ATP
PFK-1
Pi
ADP
F-1,6-BP
Lactate
AMP
Citrate
363. The significance of glycolysis
- Glycolysis is the emergency energy-yielding
pathway, such as play ball, climb mountain... - Glycolysis is the major way to produce ATP in
some tissues, even though the oxygen supply is
sufficient, such as RBC, retina, testis, skin
37Section 3 Aerobic oxidation of glucose
- The process of oxidation completely from glucose
to CO2 and H2O is named aerobic oxidation - This process is the major process to provide
energy for most tissues
38 3 phases of Glucose Aerobic oxidation
1. Oxidation from glucose to pyruvate in cytosol
(6C to 3C)
- 2. Oxidation from pyruvate to acetyl CoA in
mitochondria (3C to 2C) - 3. Tricarboxylic acid cycle and oxidative
phosphorylation (2C to 1C)
O2
O2
H2O
O2
Acetyl CoA
H e
Glucose
G-6-P
CO2
Pyruvate
Pyruvate
cytosol
mitochondria
392. Oxidation from pyruvate to acetyl CoA (3C to
2C)
NADH
Pyruvate DH complex
CoASH
NAD
Acetyl-CoA a common two-carbon unit
PyruvateNADHSCoA
Acetyl CoANADHHCO2
40Pyruvate dehydrogenase complex
E1. pyruvate dehydrogenase (??????) E2.
dihydrolipoyl transacetylase (??????????) E3.
dihydrolipoyl dehydrogenase (?????????)
41Pyruvate dehydrogenase complex
423. Two stages of the 3rd phase of Glucose
Aerobic oxidation
- Stage I The acetyl-CoA is completely oxidized
into CO2, with electrons collected by NAD and FAD
via a cyclic pathway (tricarboxylic acid cycle) - Stage II Electrons of NADH and FADH2 are
transferred to O2 via a series carriers,
producing H2O and a H gradient, which will
promote ATP formation (oxidative phosphorylation) - (NEXT CHAPTER)
43Tricarboxylic acid cycle (2C to 1C)
- Citric Acid Cycle or Krebs cycle
- Occurs in mitochondrial matrix
- Is the biochemical hub of the cell, oxidizing
carbon fuels, usually in the form of acetyl CoA,
interconversion of carbohydrates, lipids, and
some amino acids, as well as serving as a source
of precursors for biosynthesis - For the citric acid cycle, the goal is to use the
oxidative power of O2 to derive as much energy as
possible from the products of glycolysis
44Substrates required Oxaloacetic Acid
GDP 3NAD FAD two-carbon
units (Acetyl-CoA) Intermediate Reactants
Citric Acid
Each Acetyl-CoA yields 2 CO2, 3 NADH H, 1
FADH2, 1 GTP
Output Oxaloacetic Acid GTP 3 NADH
FADH2 2CO2 (4 high-energy electrons)
C6
C4
Tricarboxylic acid cycle
C5
C4
45Stage I Tricarboxylic acid cycle
CoASH
2C
Citrate synthase
6 C
4C
Citrate
Oxaloacetic Acid
46Aconitase
cis-aconitate intermediate
6 C
6 C
47Isocitrate DH
NAD
NADH
5 C
a-ketoglutarate
6 C
Isocitrate
48a-ketoglutarate DH
NAD, CoASH
NADH
5 C
4 C
Succinyl CoA
a-ketoglutarate
49CoASH
SuccinylCoA synthetase
GTP
GDP, Pi
4C
4C
Succinyl CoA
50(FADH2)
(FAD)
4C
fumarate
4C
51H2O
4C
4C
fumarate
malate
52malate DH
NAD
NADH
Oxaloacetic Acid
malate
4C
4C
53citrate synthase
Tricarboxylic acid cycle
isocitrate dehydrogenase
?- ketoglutarate dehydrogenase
54Aerobic oxidation of glucose
55 Generation of ATP in aerobic oxidation of
glucose
Reactions Catalyzed by
Methods of ATP production
formed moles of ATP
Glyceraldehyde 3-phosphate
dehydrogenase
6 or 4 /5 or 3
Respiratory chain Oxidation of 2 NADH
Glycolytic pathway
Phosphoglycerate kinase
Phosphorylation at substrate level
2
Pyruvate kinase
Phosphorylation at substrate level
2
consumption of ATP by reactions catalyzed by
hexokinase and phosphofructokinase
- 2
Production of acetyl CoA
Pyruvate dehydrogenase complex
Respiratory chain Oxidation of 2 NADH
6 or 5
Isocitrate dehydrogenase
Respiratory chain Oxidation of 2 NADH
6 or 5
Alpha-ketoglutarate Dehydrogenase complex
Respiratory chain Oxidation of 2 NADH
6 or 5
TCA cycle
Phosphorylation at substrate level
2
Succinyl CoA synthetase
Succinate dehydrogenase
Respiratory chain Oxidation of 2 FADH2
4 or 3
Malate dehydrogenase
Respiratory chain Oxidation of 2 NADH
6 or 5
Total per mole of glucose under aerobic
conditions 32 or 30(38 or 36) ATPs
56Regulation of aerobic oxidation
pyruvate
Regulation of pyruvate dehydrogenase
C2
3 control points of citric acid
cycle citrate synthase isocitrate
dehydrogenase ?-ketoglutarate dehydrogenase
C6
C4
Iso C6
Krebs Cycle
C5
C4
57 Regulation of pyruvate dehydrogenase
Inhibited by products, NADH Acetyl CoA
Also regulated by covalent modification, the
kinase phosphatase also regulated
58The Alosteric regulation of citric acid cycle
citrate synthase isocitrate dehydrogenase ?-
ketoglutarate dehydrogenase
Acetyl CoA
Oxaloacetate
ADP allosteric activator
NADH allosteric inhibitor
Allosteric inhibitor
4
GTP allosteric inhibitor
Succinate
GDP
GTP
59 Pastuer effect
- The total amount of glucose consumed by yeast are
about 7 times greater under anaerobic conditions
than under aerobic conditions - This effect is also seen in muscle under
anaerobic conditions - The yield of ATP under anaerobic conditions is 2
per molecule but under aerobic conditions the
yield is 38 ATP per glucose - Therefore, glucose flux through the pathway is
regulated to achieve constant ATP levels or
decided by the fate of NADHH - Crabtree effect
60Section 4 The Pentose Phosphate Pathway (PPP)
- The PENTOSE PHOSPHATE pathway ,by carring out
oxidation and decarboxylation of the 6-C sugar
glucose-6-P, is basically used for the synthesis
of NADPH and 5-C sugar ribulose-5-P - It plays only a minor role (compared to
GLYCOLYSIS) in degradation for ATP energy - Other names
- Pentose phosphate Shunt
- Hexose Monophosphate Shunt
61Pentose phosphate pathway
- Two stages
- Oxidative portion (NADPH producing)
- Non-oxidative (carbon recycling/unit
transferring) - Location cytosol
- Original material glucose 6-phosphate
- End product NADPH , pentose phosphate
- Important in adipose tissue, adrenal cortex,
liver (biosynthesis), Important in red blood
cells (antioxidant reasons)
62STAGE I
(OxidationNADPH producing and formation of
pentose phosphate)
NADP
H2O
NADPH H
Lactonase
G-6-P dehydrogenase
6-Phosphoglucono-?- lactone
6-Phospho- gluconate
Glucose-6-PO4
G-6-P dehydrogenase Rate limiting step,
controlled by NADP levels Glucose-6-phosphate
Dehydrogenase catalyzes oxidation of the aldehyde
(hemiacetal), at C1 of glucose-6-phosphate, to a
carboxylic acid, in ester linkage (lactone).
NADP serves as electron acceptor
63STAGE I
Ribose-5-PO4
Ribulose-5-PO4 (Ru5P)
5C
Ru5P isomerase
NADP
5C
NADPH H
Ru5P epimerase
6-phosphogluconate Dehydrogenase
6C
6-Phosphogluconate
5C
5-p-??? Xylulose-5-PO4
64STAGE II ( Non-oxidativecarbon recycling)
5C
????? 2C Transketolase
5C
Xyulose-5-PO4
Ribose-5-PO4
7-p-??? Sedoheptulose-7-PO4
7C
3C
Glyceraldehyde-3-PO4
65STAGE II ( Non-oxidativecarbon recycling)
3C
Glyceraldehyde-3-PO4
6C
Sedoheptulose-7-PO4
Fructose-6-PO4
7C
Transaldolase ????? 3C
4-p-??? Erythrose-4-PO4
4C
66STAGE II ( Non-oxidativecarbon recycling)
Glyceraldehyde-3-PO4
3C
Erythrose-4-PO4
Xylulose-5-PO4
Fructose-6-PO4
4C
5C
6C
Transketolase
glycolysis
67Pentose phosphate pathway
Glucose 6-P
6-Phosphogluconate
Ribulose 5-P (5C)
Xylulose 5-P ( 5C)
Ribose 5-P (5 C)
Glyceraldehyde 3-P
Sedoheptulose 7-P (7 C)
Glyceraldehyde 3-P (3C)
Fructose 6-P
Erythrose 4-P (4C)
Fructose 6-P (6C)
68SUMMARY
C5 C5 ? C3 C7 (Transketolase) C3 C7 ?
C6 C4 (Transaldolase) C5 C4 ? C6 C3
(Transketolase) 3 C5 ? 2 C6 C3
(Overall)
- Per glucose oxidized, 2 NADPHs are formed
- C7?C4 are strictly intermediates
- Glyceraldehyde-3-PO4 is both an intermediate and
final product - Fructose-6-PO4 is never used as an intermediate,
return to the glycolytic pathway
69 The significance of PPP
- Produce ribose 5-phosphate
- needed for DNA and RNA synthesis
- 2. Generate reducing equivalents NADPH
- 1) Reducing power for biosynthesis of fatty
acids, cholesterol, folate, and so on - 2) Coenzyme of glutathione reductase to keep
the normal level of reduced glutathione - 3) NADPH serves as the coenzyme of mixed
function oxidases (mono-oxygenases)
70Section 5Glycogen Biosynthesis and Degradation
- Introduction
- A constant source of blood glucose is an absolute
requirement for life - - glucose is the preferred energy source
for the brain and for cells with few or no
mitochondria, such as mature erythrocytes - - glucose is an essential energy source in
exercising muscle
71What is Glycogen?
a-1,6-glycosidic linkage))
Reducing end
1. Glycogen is a highly branched homopolymer of
a-glucose (polysaccharide) 2. Approx. every 10
residues there is a branch, linked by an
a-1,6-glycosidic linkage
72Glycogen Biosynthesis(Glycogenesis)
- Glycogenesis the process of storing excess
glucose as glycogen (In times of plenty the
body needs to store fuel) - occurs in the cell cytoplasm of liver, muscle
kidney, when blood glucose levels are high - Excess glucose is stored (limited capacity)
- liver and muscle are major glycogen storage sites
- liver glycogen used to regulate blood glucose
levels - brain cells cannot live for gt 5 minutes without
glucose - muscle glycogen used to fuel an active muscle
- Glycogenesis involves addition of a-D-glucose
residues to the C4 (non-reducing end) of an
pre-existing chain
73Requirement of formation glycogen
- Glycogenin
- glycogen synthase
- glycogen-branching enzyme
- UDP-glucose pyrophosphorylase
74Requirement of Formation glycogen
- Primer
- glycogenin acts as the primer to which the first
glucose residue is attached - glycogenin also catalyzes attachment of
additional glucose units to form chains of up to
eight units - Glycogen-branching enzyme
- takes over at this point
- chain cannot extend indefinitely
75Requirement of Formation glycogen
- Glycogen Synthase
- exists in an active (dephosphorylated) and
inactive (phosphorylated) form - relative amount of each form is regulated by
cellular level of cAMP - cAMP is regulated by insulinglucagon ratio
- High insulin keeps GS in dephosphorylated, active
form - High insulin can also stimulate dephosphorylation
of GS - High glucagon activates cAMP which activates PK
which phosphorylates and inactivates GS - Glycogen Synthase reaction is primary target of
insulins stimulatory effect on glycogenesis
76Glycogenesis
glycogen primer
PPi
UTP
77Glycogenesis
glycogen synthase
oligo ? 1,6-glucantransferase Debranching
glycogen synthase
oligo ? 1,6-glucantransferase Debranching
78Glycogenolysis
- Glycogenolysis glycogen ? glucose
- In times of need the body needs to mobilize its
fuel stores - Hepatic glycogen not sufficient during 12 hr fast
- Glycogen degradation
- Occurs in cytosol
- Signal that glucose is needed is given by
hormones - epinephrine stimulates glycogen breakdown in
muscle - glucagon which stimulates glycogen breakdown in
liver in response to low BG - used to sustain blood glucose level between meals
and to provide energy during an emergency/exercise
79phosphorylase a
Glycogenolysis
1,4 glucose 1-phosphate
phosphorylase a
glucan transferase
glucosidase
Debranching has two enzyme activities in one
peptide oligo -1,4 1,4-glucantransferase
and 1,6-glucosidase
1 glucose
?
?
?
phosphorylase a
12 glucose 1-phosphate
80Glycogen Phosphorylase Regulation
- Glycogen phosphorylase
- exists in a b inactive form (dephosphorylated)
and an a active form (phosphorylated) - phosphorylase kinase converts glycogen
phosphorylase to active form a via addition of
inorganic phosphate - phosphorylase kinase also exists in an active a
and an inactive b form - activated by cAMP-dependent protein kinase it is
also activated by calcium ions - PK is activated by glucagon and epinephrine
- via 2nd messenger cAMP
81Glycogen Phosphorylase Regulation
- Glycogen phosphorylase a (active) is converted
to b form by phosphoprotein phosphatase - Stimulated by insulin
- Glycogen phosphorylase can also be regulated by
allosterically - GP b inactive form can be converted to GP b
active form by high AMP - GP b active form can be converted back to GP
b inactive form by high ATP
82Regulation of Glycogenesis and Glycogenolysis
83The significance of glycogenesis and
glycogenolysis
- Liver glycogen (as much as 10 of liver wet
weight) functions as a glucose reserve for
maintaining blood glucose concentration - Muscle
glycogen (total 400 gram) serves as a fuel
reserve for synthesis of ATP within that tissue
84Section 6 Gluconeogenesis
- Synthesis of glucose from non-CHO precursors
- Lactate, most amino acids and glycerol
- Lactate and amino acids (except leucine and
lysine) are converted to either pyruvate or OAA
(oxalloacetate) - Glycerol is converted (phosphorylated) to G3P and
then to dihydroxyacetone phosphate - Occurs primarily in liver, sometimes kidney
85Ribose 5-PO4
Phosphatase
Blood Glucose
Glycogen
G6P
Glucose
Kinase
F6P
Kinase
Phosphatase
F1,6bisP
Gly-3-P
DHAP
1,3bisPGA
Gluconeogenesis
Kinase
3PGA
2PGA
PEP
Kinase
Pyruvate
OAA
L-lactate
86Gluconeogenesis
- Reversal of glycolysis except at 3 steps
- HK(GK), PFK and PK
- 3 Steps need to be bypassed
- Hexokinase and Phosphofructokinase are bypassed
by glucose 6 phosphatase and fructose
1,6-bisphosphatase - Pyruvate Kinase bypass involves formation of OAA
as an intermediate - OAA in mitochondrial matrix cannot directly cross
membrane so is converted to malate
87Gluconeogenesis
- Bypass of PK reaction continued
- Malate and aspartate can transverse mitochondrial
matrix - converted back to OAA in cytoplasm
- OAA is decarboxylated and phosphorylated to PEP
by PEP carboxykinase - Carbon skeletons of many amino acids that enter
TCA cycle can thus be used for glucose synthesis
(glucogenic amino acids)
88- Bypasses in Gluconeogenesis-1 (2 reactions)
- Pyruvate Carboxylase (Gluconeogenesis) catalyzes
- pyruvate HCO3- ATP ? oxaloacetate ADP
Pi - PEP Carboxykinase (Gluconeogenesis) catalyzes
- oxaloacetate GTP ? PEP GDP CO2
Pyruvate Carboxylase PEP Carboxykinase
-
O
O
C
-
-
O
O
O
O
A
T
P
A
D
P
P
C
O
G
T
P
G
D
P
C
C
i
-
2
C
H
C
O
P
O
C
O
2
3
-
H
C
O
C
O
3
C
2
C
H
C
H
2
3
-
O
O
pyruvate oxaloacetate
PEP
89Bypasses in Gluconeogenesis-2
glycolysis
Fructose 1,6 bi-sphosphatase
90Bypasses in Gluconeogenesis-3
- Glucose-6-Phosphatase (Gluconeogenesis)
catalyzes - glucose-6-phosphate H2O ? glucose Pi
Glucose 6 phosphatase
91 Substrate cycle is a pair of opposed
irreversible reactions
Substrate cycle or futile cycle nothing is
accomplished but the waste of ATP. In substrate
cycle, ATP is formed in one direction and then is
hydrolyzed in the opposite direction. Substrate
cycle produces net hydrolysis of ATP We
must remember that the direction of the substrate
cycle is strictly controlled by allosteric
effectors to meet the needs of the body for
energy
92Glucose Paradox
- Evidence that glucose ingested during a meal is
not used to form glycogen directly - Glucose is first taken up by RBCs in bloodstream
and converted to lactate by glycolysis - Lactate is taken up by liver and converted to G6P
by gluconeogenesis - G6P converted to glycogen
93The significance of gluconeogenesis
- To keep blood sugar level stable
- To replenish liver glycogen
- 3. To clear the products of other tissues
metabolites from the blood - 4. To convert glucogenic amino acids to glucose
- 5. To regulate acid-base balance
94 Cori Cycle(Muscles lack G6-phosphatase ) -
used to prevent high blood lactate levels and to
fuel muscle activity - l-actate leaves muscle
cells - transported via blood to liver -
liver converts to glucose - glucose released
back into circulation - returned to muscles
95Regulation of gluconeogenesis and glycolysis
F-6-P
ATP citrate ADP AMP F-2,6-BP F-1,6-BP
phosphofructokinase-1
F-1,6-biphosphatase
F-1,6-BP
insulin
gluconeogenesis
glycolysis
pyruvate carboxylase
glucokinase
phosphoenolpyruvate carboxykinase
phosphofructokinase-1
fructose 1,6-biphosphatase
pyruvate kinase
glucose 6-phosphatase
glucagon
Glucocorticoids epinephrine
96 Section VII Blood Sugar and Its
Regulation
Fate (outcome)
Origin (income)
Dietary supply
Blood sugar 3.896.11mmol/L
Liver glycogen
Gluconeoesis (non-carbohydrate)
Other saccharides
97Regulation of high Blood Sugar
4
1
2
3
5
5
glycogenolysis
6
2
98Regulation of Low Blood Sugar
cAMP
Modulating system
1
1
2
3
3
4
99????? ???
1001. ???????????( )
A ???? B ????? C ????? D ???? E ????
1012. ???????????,????( )
A ?????????? B ?????????? C ??????????? D
??????????????? E ?????????-1,6-???
1023. ????????????????( )
A ??????-1 B ??????-1 C ??????? D ?????? E
??????-2
1034. 1???????????????????????ATP??????( )
A 2 B 4 C 6 D 19 E 36
1045. 1????CoA?????????????( )
A ??? B ???? C 2CO2 4?????? D CO2H2O E
????CO2
1056. ??????????????????
A ?? B ??? C ??? D ??? E ????
1067. ???????????????????
A ??? B ??? C ??? D ???? E ???
1078. ?????????????( )
A ???????????? B ???????NADPHH C ??6-????? D
??3-????? E ??6-??????
1089. ?????????????( )
A ?????????UDPG B ?1-????????????????? C
?????????????????? D ??????????-1,4?????????? E
??????????????C4?
10910. ???????????????
A ?????? B ??????????? C ??????? D ?????? E
???6-???
11011. Which one is the main organ that regulate
blood sugar metabolism?
A brain B kidney C liver D pancreas E
adrenal gland
11112. The end product of glycolytic pathway in
human body is ( )
A CO2 and H2O B pyruvic acid C acetone D
lactic acid E oxalacetic acid
11213. Which one can promote synthesis of glucogen,
fat and protein simultaneously?
A glycagon B insulin C adrenaline D adrenal
cortex hormone E glucocorticoid
11314. Which one is the allosteric inhibitor of
6-phosphofructokinase-1?
A 1,6-diphosphofructose B 2,6
-diphosphofructose C AMP D ADP E citric acid
11415. ????????,?????????
A ?????????? B ???1????????????2??ATP C
?????????? D ??????? E ?1???????2????
11516. ??????,???????( )
A ??? ? ???? B ???? ? ?-???? C ?-???? ?
???CoA D ??? ? ???? E ??? ? ????
11617. ?????????,???????( )
A ???? B ?????? C ????? D ?????? E ?????????
11718. ??????????( )
A ?????????????? B ????????????? C ???????? D
?????? E ??????????
11819. The cofactors of pyruvic dehydrogenase
complex is ( )
A thioctic acid B TPP C CoA D FAD E NAD
11920. The high-energy compounds produced by
substrate level phosphorylation in glyco-aerobic
oxidation are ( )
A ATP B GTP C UTP D CTP E TTP
120Thank you for your tolerance!