2. ABID ALI
BS-Hons (Health & Medicine)
Khyber Medical UniversityPeshawar
2
Intermediary Metabolism
Metabolite = Biological compound
Catabolism: All the reactions concerned with breaking down compounds and generating
and storing energy for the needs of the cell and organism. Energy = ATP
Anabolism: All the reactions concerned with the biosynthesis of complex compounds
from simpler compounds. Usually use ATP
GLYCOLYSIS (Embden Myerhoff pathway)
• Glycolysis literally means "splitting sugars." In Glycolysis, glucose (a six carbon sugar)
is split into two molecules of a three-carbon sugar. Glycolysis yields two molecules of
ATP (free energy containing molecule), two molecules of pyruvic acid and two "high
energy" electron carrying molecules of NADH (Nicotinamide Adenine Dinucleotide
Hydrogen).
• It is the breakdown of glucose or glycogen up to pyruvate or lactate.
• It is a catabolic process.
• It is the main pathway of carbohydrate metabolism to generate energy i.e. ATPs.
• It occurs in the cytosol.
• It produces ATP, NADH2, and pyruvate.
TYPES OF GLYCOLYSIS
1. Aerobic Glycolysis
It takes place in the presence of O2.
3ATPs through respiratory chain, which works only in the presence of O2.
Total 10 ATPs are formed, 2 ATPs are utilized and the net gain is 8 ATPs.
2. Anaerobic Glycolysis
Takes place in the absence of O2.
End product is lactate.
Respiratory chain stops in the absence of O2. Therefore the NADH2 produced in
anaerobic Glycolysis cannot give 3 ATPs instead it reduces pyruvate to lactate.
3. ABID ALI
BS-Hons (Health & Medicine)
Khyber Medical UniversityPeshawar
3
en.w ikipedia.org
Cellular respiration: is the set of metabolic reactions and processes that take place in the cells
of organisms to convert biochemical energy from nutrients into adenosine triphosphate (ATP),
and then release waste products.
10 steps of Glycolysis (2 phases) 5 steps = 1 phase
Phase I. Energy Investment.
Enzyme= Hexokinase or glucokinase
The enzyme Hexokinase, phosphorylate (add a phosphate group to) glucose in the cell’s
cytoplasm. In the process, a phosphate group from ATP (adenosine tri phosphate) is transferred
to glucose producing glucose 6-phosphate.
Glucose (C6H12O6) +Hexokinase+ ATP → ADP +Glucose 6-phosphate (C6H11O6P1)
This means thatan enzyme with quaternarystructure can bind more than one substrate molecule.Allosterymeans
"different shape."Allosteric enzymes change shape between active and inactive shapes as a resultofthe binding of
substrates atthe active site,and of regulatory molecules atother sites.
STEP-1
GLUCOKINASE
Present only in liver.
Its activity depends upon the
nutritional state of glucose i.e.
it becomes active only when
sufficient quantity of glucose
is present.
It is a high Km value.
It is not an allosteric enzyme.
HEXOKINASE
Present in liver as well as in other body
tissues.
Its activity does not depend upon the
nutritional state of glucose i.e. it
remains active even at low glucose
concentration.
It has a low Km value.
It is an allosteric enzyme,
4. ABID ALI
BS-Hons (Health & Medicine)
Khyber Medical UniversityPeshawar
4
Isomerization of glucose 6-phosphate Enzyme = phophoglucoisomerase
The enzyme phophoglucoisomerase converts glucose 6-Phosphate into its isomer fructose 6-
Phosphate. Isomers have the same molecular formula but the atoms of each molecule are
arranged differently.
Glucose 6-Phaphate (C6H12O6P1) + Phophoglucoisomerase → Fructose 6-Phosphate (C6H11O6P1)
Second phosphorylation Enzyme = Phosphofructokinase
The enzyme Phosphofructokinase use another ATP molecule to transfer a phosphate group to
fructose 6-Phosphate to form fructose 1, 6-Biphosphate.
Fructose 6-Phosphate (C6H11O6P1) + Phosphofructokinase+ ATP → ADP+ Fructose1, 6-biphosphate(C6H10O6P2)
STEP-2
STEP-3
5. ABID ALI
BS-Hons (Health & Medicine)
Khyber Medical UniversityPeshawar
5
Cleavage to two Triose phosphates Enzyme = Aldolase
The enzyme Aldolase splits fructose 1, 6-biphosphate into two sugars that are isomers of each
other. These two sugars are Dihydroxyacetone phosphate (DHAP) and Glyceraldehydes phosphate
(GAP).
Fructose 1, 6-biphosphate (C6H10O6P2) + Aldolase → Dihydroxyacetone phosphate (C3H5O3P1) +
Glyceraldehyde phosphate (C3H5O3P1).
Isomerization of Dihydroxyacetone phosphate .Enzyme = Triose-phosphate isomerase
The enzyme Triose phosphate isomerase rapidly inters converts the molecules Dihydroxyacetone
phosphate (DHAP) and Glyceraldehydes phosphate (GAP). Glyceraldehyde phosphate is removed as soon
as it’s formed to be used in the next step of Glycolysis.
Dihydroxyacetone phosphate (C3H5O3P1) → Glyceraldehyde phosphate (C3H5O3P1).
End of First Phase:
Production of two Glyceraldehyde
3-phosphate molecules from one
Glucose molecule with the
Expenditure of two ATPs.
Therefore: the product & energy
Yields of the following steps are
Multiplied by two relative to glucose
STEP-5
STEP-4
6. ABID ALI
BS-Hons (Health & Medicine)
Khyber Medical UniversityPeshawar
6
SecondPhase-EnergyPayoff
Oxidation of Glyceraldehyde 3-phosphate (Enzyme= glyceraldehyde-3-phosphate dehydrogenase)
The enzyme Triose phosphate dehydrogenase serves two functions in this step. First the enzyme
transfers hydrogen (H) from Glyceraldehyde phosphate to the oxidizing agent Nicotinamide
adenine Dinucleotide (NAD) to form NADH. Next Triose phosphate dehydrogenase adds a
phosphate (P) from the cytosol to the oxidized Glyceraldehyde phosphate to form 1, 3
Bisphosphoglycerate. This occurs for both molecules of Glyceraldehyde phosphate produced in
step-5.
A). Triose phosphate dehydrogenase + 2 H+ 2 NAD+ → 2 NADH + 2 H+.
B). Triose phosphate dehydrogenase + 2 P + 2 Glyceraldehyde phosphate (C3H5O3P1) → 2
molecules of 1, 3 Bisphosphoglycerate (C3H4O4P2).
Transfer phosphate to make ATP Enzyme = phosphoglycerate kinase
The enzyme phosphoglycerokinase transfers a (P) from 1,3 Bisphosphoglycerate to a molecule
of ADP to form ATP. This happens for each molecule of 1, 3 Bisphosphoglycerate. The process
yields two molecules and two ATP molecules.
2 molecules of 1, 3 Bisphosphoglycerate (C3H4O4P2) + phosphoglycerokinase + 2 ADP→ 2
molecules of 3-phosphoglycerate (C3H5O4P1) + 2 ATP.
STEP-6
STEP-7
7. ABID ALI
BS-Hons (Health & Medicine)
Khyber Medical UniversityPeshawar
7
Phosphate shift setup Enzyme= phosphoglycerate mutase
The enzyme phosphoglyceromutase relocates the (P) from 3-phosphoglycerate from the third
carbon to the second carbon to form 2-phosphoglycerate.
2 molecules of 3-phosphoglycerate (C3H5O4P1) + phosphoglyceromutase → 2 molecules of 2-
phosphoglycerate (C3H5O4P1).
Generation of second very high-energy compound by a dehydration. Enzyme = enolase
The enzyme enolase removes a molecule of water from 2-phosphoglycerate to form
phosphoenolpyruvic acid (PEP). This happens for each molecules of 2-phosphoglycerate.
2 molecules of 2-phophoglycerate (C3H5O4P1) + enolase → 2 molecules of phosphoenolpyruvic acid
(C3H3O3P1).
Final generation of ATP. Enzyme = pyruvate kinase
The enzyme pyruvate kinase transfers a (P) from phosphoenolpyruvic acid to ADP to form
pyruvic acid and ATP. This happen for each molecules of phosphoenolpyruvic. This reaction
yields 2 molecules of pyruvic acid and 2 ATP molecules.
2 molecules of phosphoenolpyruvic acid (C3H3O3P1) + pyruvate kinase + 2 ADP → 2 molecules of
pyruvic acid (C3H4O3) + 2 ATP.
STEP-8
STEP-9
STEP-10
8. ABID ALI
BS-Hons (Health & Medicine)
Khyber Medical UniversityPeshawar
8
Summary
A single glucose molecule in Glycolysis produces a total 2 molecules of pyruvic acid, 2
molecules of ATP, 2 molecules of NADH and 2 molecules of water.
Although 2 ATP molecules are used in step 1, 3, 2 ATP molecules are generated in step 7 and 2
more in step 10. This gives a total 4 ATP produced. If you subtract 2 ATP molecules used in step
1-3 from the 4 generated at the end of step 10, you end up with a net total of 2 ATP molecules
produced. For a detailed view of the 10 steps, see: details of the 10 steps of Glycolysis.
Overall net equation is:
Glucose+ 2NAD+ 2ADP + 2Pi → pyruvate + 2 NADH+ 2 ATP + 2 NAHD+ 2 H+ 2 H2O
Glycolysis is exergonic (Releasing energy) produces net 2 ATPs 2NADHs.