NS101/BIOENG 103/ HBMANI 104

Carbohydrate metabolism:
Glycolysis

Ms R. Makurira
Glycolysis
 It is also called as Embden Meyerhoff pathway
 Oxidation of glucose

- to form pyruvate and lactate

 This pathway is unique in the sense that it can

utilize O2 if available (‘aerobic’) and it

can function in absence of O2 also (‘anaerobic’)
 It occurs virtually in all tissues.
- Erythrocytes and nervous tissues derive its energy
mainly form glycolysis.
Significance of the pathway
 This pathway is meant for provision of energy.

 It has importance in skeletal muscle as

glycolysis provides ATP even in absence of O2,
muscles can survive under anaerobic condition.
Aerobic Phase
 Aerobic phase includes the conversion of
glucose to pyruvate

 Oxidation is carried out by dehydrogenation and

reducing equivalent is transferred to NAD.

 NADH + H+ in presence of O2 is oxidized in

electron- transport chain producing ATP.
Anaerobic Phase
 Includes the conversion of glucose to lactate

- NADH is oxidized to NAD+ by conversion of pyruvate to

lactate, without producing ATP.
Reactions of Glycolytic pathway
Stage I: Priming

 glucose molecule is converted to fructose 1, 6

bisphosphate
- input of 2 ATP molecules.
(a). Uptake of Glucose by Cells and its
phosphorylation
 Glucose is freely permeable to liver cells.
 In Intestinal mucosa and kidney tubules, glucose

is taken up by ‘active’ transport.

 In other tissues, like skeletal muscle, cardiac

muscle, diaphragm, adipose tissue etc. Insulin

facilitates the uptake of glucose.
 Glucose is then phosphorylated to form glucose

– 6- Phosphate.
-The reaction is catalyzed by the specific enzyme
glucokinase in liver cells and by nonspecific Hexokinase in
liver and extrahepatic tissues.
 ATP acts as PO4 donor in the presence of Mg .
- One high energy PO4 bond is utilized and ADP is
produced.
 Glucose 6 phosphate formed is an important
compound at the junction of several metabolic
pathways like glycolysis, glycogenesis,
glycogenolysis, gluconeogenesis,
Hexosemonophosphate Shunt, uronic acid
partway. Thus is a “committed step” in metabolic
pathways.
(b). Conversion of G- 6- phosphate to
Fructose 6-phosphate
 Glucose 6 phosphate after formation is
converted to fructose 6-p by phospho-hexose
isomerase
 which involves an aldose- ketose isomerization
(c). Conversion of Fructose 6 phosphate to
Fructose 1, 6 bisphosphate
 is another phosphorylation reaction.

 Fructose-6-p is phosphorylated with ATP at 1-

position
 catalyzed by the enzyme phospho- fructokinase-
1
 to produce fructose 1, 6 bisphosphate.
Note
 reaction one is irreversible

 2 ATP molecules are utilized for phosphorylation

 Phosphofructokinase I is the key enzyme in

glycolysis that regulates the pathway.
- The enzyme is inducible, as well as allosterically
modified
Energetics
 Note that in this stage glucose oxidation does
not yield any useful energy rather there is
expenditure of 2 ATP molecules for two
phosphorylations (-2 ATP).
Stage II: Spliting
 fructose 1, 6- bisphosphate is split by the
enzyme aldolase

- into 2 molecules of triose phosphates;

1. an aldotriose- glyceraldehyde 3 phosphate
2. a ketotriose- dihydroxyacetone phosphate.
Note
 The reaction is reversible

 There is neither expenditure of energy nor

formation ATP

 Both triose phosphates are interconvertable

Stage III: oxidoreduction-
phosphorylation
 Energy- yielding reaction

 An aldehyde group is oxidized to an acid and

accompanied by liberation of large amounts of
potentially useful energy.
(a). Oxidation of Glyceraldehyde 3
phosphate to 1,3 bis phosphoglycerate
 Glyceraldehde-3-phosphate is oxidized to a
carboxylic acid; 1,3-bisphosphoglycerate.

 The enzyme responsible is Glyceraldehyde 3

phosphate dehydrogenase, which is NAD+
dependant.
- NAD+ is reduced to NADH
(b) Formation of 3- phosphoglycerate
 Reaction catalysed by phosphoglycerate kinase

 1st reaction to produce ATP

- substrate level phosphorylation

 2 molecules of 1,3 bisphosphoglycerate,

therefore, 2ATP are produced and recover the 2
used in priming
(c). Conversion of 3- phosphoglycerate to 2-
Phosphoglycerate

 3-Phosphoglycerate formed by the previous

reaction is converted to 2-phosphoglycerate,
- catalyzed by the enzyme phosphoglycerate
mutase.
(d). Conversion of 2-phosphoglycerate
to Phosphoenol pyruvate
 The reaction is catalyzed by the enzyme
enolase
- the enzyme requires the presence of
either Mg2+ or Mn2+ for activity.

 The reaction involves dehydration of 2-

phosphoglycerate to form PEP
(e). Conversion of phosphoenol
pyruvate to pyruvate
 Phosphoenol pyruvate is converted to pyruvate
- catalyzed by the enzyme pyruvate kinase.

 The high energy PO4 of phosphoenol pyruvate is

directly transferred to ADP producing ATP.
Note
 Reaction is irreversible
 ATP is formed at the substrate level without

electron transport chain.

- This is an example of “ substrate level
phosphorylation “ in glycolytic pathway
Significance of lactate formation
 Under anaerobic conditions NADH is re oxidized
via lactate formation. This allows glycolysis to
proceed in the absence of oxygen.

 The process generates enough NAD for another

cycle of glycolysis.
Summary- Glycolysis