Glycolysis

CARBOHYDRATE METABOLISM – TOPIC 1

Objectives

• Students should be able to:

• State the significance of glycolysis in living cells
• Describe how glucose enters the liver and peripheral tissues
• Describe the phases of glycolysis
• Should be able to explain the importance of :
• The committed step in glycolysis
• Key intermediates in the glycolytic pathway which are also
common intermediates in other metabolic pathways
• Identify the irreversible steps in glycolysis
• Identify the steps where ATP is utilized
• Identify the steps where ATP and NADH are synthesized
• Describe the fates of pyruvate and explain how it is utilized to
synthesize ATP under aerobic and anaerobic conditions
• Describe how other sugars enter the glycolytic pathway
 Glycolysis

• also called Embden-Meyerhof pathway (E.M-Pathway).

• It occurs in cytosol
• 10 step catabolic pathway
• Objective of pathway
• to produce energy (ATP) and the reducing agent (NADH) from
catabolizing hexose sugars
• Can occur aerobically or anaerobically
 Sources of
Carbohydrates
 • Glycolysis is a major pathway for ATP
synthesis in tissues lacking mitochondria -
erythrocytes, cornea, lens etc.
Importance • Glycolysis is very essential for brain tissues
of Glycolysis which is dependent on glucose for energy.
• Independently, it can catabolize carbs
anaerobically unlike many other energy
yielding substrates
• Glycolysis is a central metabolic pathway
• Many of its intermediates are primary
substrates or shared intermediates for
other pathways e.g. glycogen synthesis, the
Pentose Phosphate Pathway, fatty acid
synthesis, amino acid synthesis etc.
 • Glucose transporters (GLUT) are transmembrane
proteins that facilitate entry into cells - bidirectional
• GLUT -1
• Found in all cells of the body
Glucose • Blood glucose level is ~5mM but this transporter
has a KM of 1mM – high affinity for glucose
Entry Into • GLUT – 3
Cells • Similar to GLUT-1
• Found in neural tissue in the brain
• GLUT – 2
• Found primarily in the β-cells of the pancreas but
also in liver, kidney and intestines
• Has a high Km value (~15mM) which means
pancreas will only respond to glucose in high conc
• GLUT-4
• Found in muscle, heart and adipose tissue
• Sensitive to insulin – causes increased production
and presence in membrane
• Km = 5mM.
Entry of Glucose into Cells
Phases of Glycolysis
• Divided into three distinct
phases.
1. Energy investment phase
or priming phase
2. Splitting phase
3. Payoff phase.
Energy Investment & Splitting Phases

• Glucose is obtained
from diet via intestinal
hydrolysis of lactose,
sucrose, maltose,
glycogen, or starch

• Can be synthesized in
the liver from non-
glucose precursors and
released into the blood
to be used by other
tissues
 • Phosphorylated sugar molecules do not
readily penetrate cell membranes without
specific carriers
• this commits glucose to further metabolism
in the cell.
• One of 3 key regulatory enzymes of glycolysis.
Hexokinase • Hexokinase
• Allosterically inhibited by glucose-6-PO4
Reaction • Allosterically stimulated by Pi
• Step is irreversable
Hexokinase vs Glucokinase
 Phosphofructokinase Reaction

• Fructose 6- phosphate is phosphorylated to Fructose-1, 6-

bisphosphate by Phosphofructokinase (PFK-1)
• The PFK reaction is the rate-limiting step.
• Enzyme allosterically activated by ADP and AMP conc
• Inhibited by ATP and citrate (high energy)
• Irreversible reaction
PFK2 and Regulation
The
Payoff
Phase
Regulation of Pyruvate Kinase
Regulation of Pyruvate Kinase
Fates of Pyruvate
Energetic Fates of Pyruvate
 Fates of Pyruvate – Acetyl CoA

• In the presence of O2 pyruvate enters the mitochondria

(outer – aquaporin, inner – pyruvate translocase in symport
with H+)
• Where it is oxidatively decarboxylated to acetyl CoA and
enters the TCA
Aerobic Fate of Pyruvate
 Fates of Pyruvate - Lactate

• During glycolysis NAD+ is reduced NADH

• NADH in the cytosol is limited

• Problem – without oxygen NADH cannot be re-oxidized back to

NAD+ and glycolysis will stop

• Solution:
 Fates of
Pyruvate -
Lactate
Summary
Gluconeogenesis
• Gluco – sugar (think glucose)
• Neo – new
• Genesis – origin

• Pathway synthesizes glucose from non-

carbohydrate precursors namely:
• Alcohols – glycerol
• Amino acids
• Lactate
• pyruvate
Entry of Gluconeogenic Substrates
Entry of Amino Acids into
Gluconeogenesis
Gluconeogenesis – Bypass
Reactions
• Glycolysis has 3
irreversible
reactions
• In order to
synthesize glucose,
these reactions
must be bypassed
Reciprocal
Regulation of
Glycolysis &
Gluconeogenesis