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Glycolysis (Greek: glycos=sugar; lysis=

breaking or splitting or loosening)


Also called the Embden-Meyerhof Pathway.
Function: The major pathway for glucose
(and other hexoses such as fructose,
galactose, and mannose) utilization to provide
energy (ATP).
Glucose is the preferred energy source
Site: Cytoplasm of all cells/ Cytosol
Types:
o Aerobic: uses O2; pyruvate is the end
product.
o Anaerobic: uses no O2; lactate is the end
product.
Phases of Glycolysis
A. FIRST PHASE- First 5 reactions
Energy investment phase
o ATP (2 moles of ATP) is utilized in the
synthesis of phosphorylated forms of glucose
and fructose.
Priming phase or Preparatory or collection
phase
because glucose and a number of hexoses
after phosphorylation by ATP undergo
catabolism and then cleaved to form
glyceraldehyde 3-phosphate.
B. SECOND PHASE- Last 5 reactions
Energy generation phase or payoff phase
o Net of two (2) molecules of ATP formed per
molecule of glucose oxidized to pyruvate or
lactate.

III. Reactions of Glycolysis


Phase 1: ENERGY INVESTMENT
Stage 1: Priming Stage - -Involves input of 2
molecules of ATP to convert glucose into
fructose 1,6 bisphospate.
-ATP is invested rather than lost in this
stage.
D-Glucose + 2 ATPD-fructose 1,6
bisphospate + 2 ADP + 2 H+
Glucose, coming from the blood, enters the
cell membrane via specific transport proteins
(facilitated transport system for extrahepatic
cells in the presence of insulin; in liver cells,
entry of glucose is via an insulin
independent facilitated transport system)
Enzyme: Transferases Hexokinase
(Hexokinase I, II, III)
-Present in all extrahepatic
cells -low Km (<0.1Mm), high affinity
for glucose (assures efficient
phosphorylation and
subsequent glucose
metabolism).
-requires ATP complexed with Mg2+
(True substrate of the enzyme is not ATP,
but the Mg-ATP complex.
All kinases require Mg2+).
Glucokinase (Hexokinase IV, an isoenzyme of
hexokinase)
Present only in liver and pancreatic B cells.
High Km, low affinity for glucose. This enzyme
is not allosterically regulated by high glucose6- phosphate concentrations. The high Km

means that glucokinase only becomes


metabolically important when glucose levels
are high (after a CHO-rich meal, with a
temporary high concentration of blood
glucose, glucokinase becomes active).
Produces glucose-6-phospate which is then
stored in the liver in the form of glycogen.
Indirectly regulated by fructose- 6-phosphate
(binds glucose to glucokinase inhibitory
protein, GK-RP, which translocates to nucleus;
reversed by glucose, fru c to s e-1phosphate) Biomedical importance: sensor for
blood glucose
This initial glucose phosphorylation is a very
important step in glycolysis.
In the cytoplasm, hexokinase or glucokinase
catalyzes the transfer of -phosphate group of
ATP (the terminal phosphate group) to the O2
atom of C-6 of glucose to form a phosphate
ester glucose 6- phosphate and ADP with
Mg2+ as a cofactor.
The reaction is highly exergonic because the
G is -4.0 kcal/mole, hence a
thermodynamically favorable, irreversible
reaction under cellular conditions.
Reaction catalyzes the 1st molecule of ATP
1st irreversible reaction of glycolysis
This step commits glucose to metabolism.
The C-6 hydroxyl O2 of glucose
nucleophilically attacks - phosphorus of
MgATP2 Phosphorylation prevents leakage out of the
cell because there are no transporters for
glucose 6-PO4

The conversion of glucose to glucose-6phosphate makes it stay inside the cell.