Download carbohydrate metabolism: glycolysis

CARBOHYDRATE
METABOLISM: GLYCOLYSIS
KHADIJAH HANIM ABDUL RAHMAN
SCHOOL OF BIOPROCESS ENGINEERING,
UNIMAP
WEEK 14: 10/12/2012
SEM1, 2012/2013
Learning Outcomes
 Able to ILLUSTRATE processes involved in cellular
respiration comprise of Glycolysis, Citric acid Cycle
Electron Transport Chain and photosynthesis.
Introduction
 Glycolysis- metabolic pathway that converted a
glucose into 2 pyruvate molecules.
• excess glucose- converted
into glycogen by
glycogenesis
• when glucose is neededglycogen degraded to
glucose by glycogenolysis
• in some cells, glucose is
converted to ribose-5phosphate and NADPH by
pentose phosphate pathway
• glucosepyruvate,
energy-generating
pathway, glycolysis.
•In the absence of O2,
pyruvate  lactate
Major pathways in
Carbohydrate metabolism
GLYCOLYSIS
 Enzymes and mechanisms that are involved in the
pathway are highly homologous in prokaryotes and
eukaryotes.
 In glycolysis, each glucose (C6H12O6) molecule is split
and converted to 2 three-carbon units known as
pyruvate (CH3COCOO- + H+).
 The small amount of energy captured during
glycolytic reactions is stored temporarily in 2
molecules each of ATP and NADH.
 In anaerobic organisms (without O2 to generate
energy), pyruvate converted to waste products ie.
Ethanol, lactic acid, acetic acid and etc.
 Using O2 as terminal acceptor, aerobic organisms
completely oxidized pyruvate to form CO2 and H2Oprocess known as aerobic respiration.
 Glycolysis, which consists of TEN reactions, occurs in 2
stages:
1) Glucose is phosphorylated twice and cleaved to form 2
molecules of glyceraldehyde-3-phosphate (G-3-P). The
2 ATP molecules consumed during this stage are like an
investment- this stage create the actual substrate for
oxidation.
2) G-3-P is converted to pyruvate. 4 ATP molecules and 2
NADH are produced. Since 2 ATP molecules are
consumed in stage 1, the net ATP molecules produced
is 2 molecules.
 The glycolytic pathway equation:
D-Glucose + 2ADP + 2Pi + 2 NAD+  2 pyruvate +
2 ATP + 2 NADH + 2H+ + 2H2O
The reactions of the glycolytic pathway
1) Synthesis of glucose-6-phosphate
-
After entering a cell, glucose and other sugar
molecules are phosphorylated.
Phosphorylation-prevents transport of glucose out
of the cell and increases the reactivity of O2 in the
resulting phosphate ester
2) Conversion of glucose-6-phosphate to fructose-6-phosphate
- The aldose glucose-6-phosphate is converted to the ketose
fructose-6-phosphate by phosphoglucose isomerase (PGI) in a
readily reversible reaction
- This transformation makes C-1 of the fructose available for
phosphorylation
3) Phosphorylation of fructose-6-phosphate
- Phosphofructokinase-1 (PFK-1) catalyzes the
phosphorylation of fructose-6-phosphate to form
fructose-1,6-biphosphate:
- The 2nd molecule of ATP serves as:
- Phosphorylating agent
- To prevent any later product from diffusing out of
the cell- fructose-1,6-biphosphate splits into 2
trioses.
4) Cleavage of fructose-1,6biphosphate
- Stage 1 of glycolysis ends
by cleaving fructose-1,6biphosphate into 2 threecarbon molecules: G-3-P
and dihydroxyacetone
phosphate (DHAP).
- In aldol cleavage:
products are aldehyde
and a ketone.
5) The interconversion of G-3-P and dihydroxyacetone
phosphate.
- Only G-3-P serves as substrate for the subsequent
reaction of glycolysis.
- To prevent the loss of the other 3-carbon unit from
the glycolytic pathway, triose phosphate isomerase
catalyzes the interconversion of DHAP and G-3-P:
6) Oxidation of glyceraldehyde-3-phosphate
- G-3-P undergoes oxidation and phosphorylation.
- The product glycerate-1,3-biphosphate contains a
high-energy bond- used in the next reaction to
generate ATP:
7) Phosphoryl group transfer
- In this reaction, ATP is synthesized as
phosphoglycerate kinase catalyzes the transfer of the
high-energy phosphoryl group of glycerate-1,3biphosphate to ADP:
8) The interconversion of 3-phosphoglycerate and 2phosphoglycerate
- In the first step of this conversion- phosphoglycerate
mutase catalyzes the conversion of C-3
phosphorylated compound to a C-2 phosphorylated
compound thru a 2-step addition/elimination cycle.
- Glycerate-3-phosphate has a low phosphoryl group
transfer potential.
- It is a poor candidate for further ATP synthesis
- Cells convert glycerate-3-phosphate with its energypoor phosphate ester to phosphoenolpyruvate
(PEP)- has high phosphoryl group transfer potential
9) Dehydration of 2phosphoglycerate
- Enolase catalyzes the
dehydration of glycerate-2phosphate to form PEP
- PEP has a higher phosphoryl
group transfer potential than
glycerate-2-phosphate- it
contains an enol-phosphate
group instead of a simple
phosphate ester.
10) Synthesis of pyruvate
- In the final reaction of glycolysis, pyruvate kinase
catalyzes the transfer of a phosphoryl group from
PEP to ADP
- 2 molecules of ATP are formed for each molecule of
glucose.
FATES OF PYRUVATE
 Glycolysis- produced 2 molecules of ATP and 2
molecules of NADH per molecule of glucose
 Pyruvate is the product of glycolysis that has a highenergy which can produce a substantial amount of
ATP. Before this can happen however, an
intermediate molecule called acetyl-CoA is formed
thru decarboxylation.
 Acetyl-CoA- substrate for TCA cycle.
 TCA cycle- an amphibolic pathway that completely
oxidizes 2 Carbons to CO2 and NADH
 In the presence of O2, this cycle is kept going.
 The electrons of NADH (and FADH2, another
electron carrier) produced in TCA cycle are delivered
to O2 via the electron transport system to produce
water.
 Electron transport system- a linked series of
oxidation-reduction reactions that transfer electrons
from donor, NADH to acceptor, O2.
 Under anaerobic conditions, further oxidation of
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pyruvate is impeded.
A no of cells and organisms compensate by converting
this molecule to a more reduced formed and regenerating
NAD+ required for glycolysis to continue.
The regeneration of NAD+ is referred as fermentation.
Muscle cells and certain bacteria produce NAD+ by
transforming pyruvate into lactate.
In rapidly contracting muscle cells the demand for
energy is high.
After the O2 supply is depleted, lactic acid fermentation
provides sufficient NAD+ to allow glycolysis to continue.
i
 Microorganisms that use lactic acid fermentation to
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generate energy can be seperated into 2 groups:
Homolactic fermenters- produce only lactate
Heterolactic/mixed acid fermenters- produce several
organic acids. Eg occurs in rumen of cattle.
Symbiotic organisms, digest cellulose and synthesize
organic acids (lactic, acetic, propionic acids).
The organic acids are absorbed from the rumen and
used as nutrients.
 Alcoholic fermentation- in yeast and several bacterial
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species
In yeast, pyruvate is decarboxylated to form
acetaldehyde, which is then reduced by NADH to
form ethanol.
Alcoholic fermentation by several yeasts is used
commercially to produce beer, wine and bread
Certain bacterial species capable of producing
alcohol other than ethanol
Eg Clostridium acetobutylicum- produces butanol.
Butanol- detergents and synthetic fibres.
Fates of Pyruvate