Glycolysis and gluconeogenesis
Post on 10-May-2015
20986 Views
Preview:
DESCRIPTION
Transcript
GLYCOLYSIS AND GLUCONEOGENESIS
INSTRUCTOR-RCL
GROUP 4
NITI KR. SHAHANUP BIK. SHAH
REVOLUTION SHERETHA SMIRITI KHADKA
BIJAY RAJBANSHI TAKAR ABDIGANI
Glycolysis (Embden-Meyerhof pathway)
• Glycolysis is the breakdown of glucose into pyruvic acid
• Does not require oxygen
• Occurs free in the cytoplasm
• Begins with D-glucose as the substrate
The two parts of glycolysis:
glucose glucose 6-phosphate fructose 1,6- diphosphate
Part one(enery invesment phase):
ATP ATP
Part two(energy generating phase):
fructose 1,6-diphosphate
2 ATP 2 ATP2 NADH
2 pyruvic acid
Glycolysis
• Overall net equation is:Glucose + 2NAD + 2ADP + 2Pi 2 pyruvates +
2NADH + 2 ATP + 2 NADH + 2 H+ + 2 H2O
• Glycolysis is exergonic - produces net of 2ATPs and 2NADHs
Glycolysis
• Coenzyme NAD+ is a biological oxidizing agent that converts C-H bonds to C-O bonds. In the process, NAD+ is reduced to NADH + H+.
• The phosphorylation of ADP requires energy and forms ATP, a high-energy nucleoside triphosphate.
• The hydrolysis of ATP releases energy and forms ADP
Steps in glycolysis • Step 1• Substrate glucose is phosphorylated by
hexokinase• Product is glucose-6-phosphate
– Source of the phosphoryl group is ATP– Expenditure of ATP early in the pathway
works as energy “debt” necessary to get the pathway started
Step 1
Step 2• Product of step 1 is rearranged to the
structural isomer fructose-6-phosphate by enzyme phosphoglucose isomerase
- Converts and aldose to a ketose
Step 3• Substrate fructose-6-phosphate
is phosphorylated by phosphofructokinase
• Product is fructose-1,6-bisphosphate– Source of the phosphoryl group is ATP
•
Step 4• Product of step 3 is split into two 3-
carbon intermediates by the enzyme aldolase forming:– Glyceraldehyde-3-phosphate (substrate of
next reaction)– Dihydroxyacetone phosphate
Step 5• Dihydroxyacetone phosphate is
rearranged into a second glyceraldehyde-3-phosphate by the enzyme triose phosphate isomerase– Glyceraldehyde-3-phosphate is the only
substrate for the next reaction
Step 6• Substrate glyceraldehyde-3-phosphate is
oxidized to a carboxylic acid by glyceraldehyde-3-phosphate dehydrogenase– Reduces NAD+ to NADH
• Product is 1,3-Bisphosphoglycerate – New phosphate group attached with a “high-
energy” bond
Step 7• Harvest energy in the form of ATP• 1,3-Bisphosphoglycerate high energy
phosphate group is transferred to ADP by phosphoglycerate kinase:– 3-Phosphoglycerate– ATP
• This is the first substrate level phosphorylation of glycolysis
Step 8• 3-Phosphoglycerate is isomerized into 2-
phosphoglycerate by the enzyme phosphoglycerate mutase– Moves the phosphate group from carbon-3 to
carbon-2
Step 9• The enzyme enolase catalyzes
dehydration of 2-phospholgycerate– Phosphoenolpyruvate
• Energy rich – highest energy phosphorylated compound in metabolism
Step 10• Final substrate-level dehydration in the
pathway• Phosphoenolpyruvate serves as donor of
the phosphoryl group transferred to ADP by pyruvate kinase making ATP and releasing water– Pyruvate is the final product of glycolysis
Summary of glycolysis
Net result of glycolysis• The final products are:
– Two pyruvic acid molecules– Two NADH + H+ molecules
(reduced NAD+)– A net gain of two ATP molecules
• Fructose is obtained by the hydrolysis of the disaccharide sucrose, found in sugar beets and sugarcane
• Galactose is obtained by the hydrolysis of the dissacharide lactose in milk
• Mannose is obtained from polysaccharides in fruits such as cranberries and currants
Glycolysis and other hexoses
Acetyl CoA, CH₃COSCoA, is formed under aerobic conditions
Lactate, CH₃CH(OH)CO2⁻, is formed under anaerobic conditions.
Ethanol CH₃CH2OH, is formed in fermentation
Fate of pyruvate
Gluconeogenesis: The Synthesis of Glucose
• Gluconeogenesis makes glucose from noncarbohydrate starting materials – Lactate– Glycerol– Most amino acids (not leucine,
lysine)– Glycerol and amino acids are used
only in starvation conditions• Process occurs primarily in the
liver
The gluconeogenic pathway converts pyruvate into glucose.
pyruvate glucose→→ → → →
gluconeogenesis
glycolysis
Gluconeogenesis is not a reversal of glycolysis
Comparison of Glycolysis
and Gluconeogenesis• While basically opposite processes
glycolysis and gluconeogenesis are not a simple reversal of each other
• The three nonreversible steps of glycolysis must be bypassed with new routes– Pyruvate Phosphoenolpyruvate – Fructose-1,6-bisphosphate Fructose-6-
phosphate– Glucose-6-phosphate Glucose
Comparison of Glycolysis and Gluconeogenesis
Pyruvate Phosphoenolpyruvate
• The two enzymes that catalyze the reactions for bypass of the Pyruvate Kinase reaction are the
following:
• Pyruvate Carboxylase (Gluconeogenesis) catalyzes:pyruvate + HCO3
- + ATP oxaloacetate + ADP + Pi
• PEP Carboxykinase (Gluconeogenesis) catalyzes:oxaloacetate + GTP PEP + GDP + CO2
C
C
CH 2
O O
O PO 32
C
C
CH 3
O O
O
A T P A D P + P i C
CH 2
C
C
O
O O
O O
HC O 3
G T P G D P
CO 2
p y r u v a te o x a lo a c e ta te P E P
P y ru v a te C a rb o x y la s e P E P C a rb o x y k in a s e
Fructose-1,6-bisphosphate Fructose-6-phosphate
• Fructose 6-phosphate is formed from 1,6-bisphosphate by hydrolysis of the phosphate ester at carbon1.Fructose 1,6-bisphosphatase catalyzes this exergonic hydrolysisFructose 1,6-bisphosphate + H2O
fructose 6-phosphate + Pi
Glucose-6-phosphate Glucose• Glucose is formed by the hydrolysis
of gulcose 6-phosphate in a reaction catalyzed by gulcose 6-phosphate
Gulose 6-phosphate + H2O gulcose + Pi
Glyceraldehyde-3-phosphate Dehydrogenase
Phosphoglycerate Kinase
Enolase
PEP Carboxykinase
glyceraldehyde-3-phosphate
NAD+ + Pi
NADH + H+
1,3-bisphosphoglycerate
ADP
ATP
3-phosphoglycerate
Phosphoglycerate Mutase
2-phosphoglycerate H2O
phosphoenolpyruvate
CO2 + GDP
GTP oxaloacetate
Pi + ADP
HCO3 + ATP
pyruvate
Pyruvate Carboxylase
Gluconeogenesis
Summary of Gluconeogenesis
Pathway:
Gluconeogenesis enzyme names in
red.
Glycolysis enzyme names in blue.
Glucose-6-phosphatase
Fructose-1,6-bisphosphatase
glucose Gluconeogenesis
Pi
H2O glucose-6-phosphate
Phosphoglucose Isomerase
fructose-6-phosphate
Pi
H2O fructose-1,6-bisphosphate
Aldolase
glyceraldehyde-3-phosphate + dihydroxyacetone-phosphate
Triosephosphate Isomerase (continued)
Gluconeogenesis Regulation• Step 3 of glycolysis:
– Catalyzed by phosphofructokinase
– Stimulated by: high AMP, ADP, Pi
– Inhibited by: high ATP• Reverse occurs in gluconeogenesis:
– Fructose-1,6-bisphosphatase stimulated by high ATP
– At times of excess energy (high ATP) gluconeogenesis is favored
Reciprocal regulation of gluconeogenesis and glycolysis in
the liver.
The interconversion of fructose 6-phosphate
and fructose 1,6-bisphosphate
is stringently controlled
The interconversion of phosphoenolpyruvate and pyruvate also is
preciselyregulated.
Cori Cycle
• In the Cori cycle,– Lactate from skeletal muscle is
transferred to the liver – Converted to pyruvate then glucose – This glucose can be returned to the
muscle
THANKS
top related