Glucose Metabolism: An
Overview
By
Reem Sallam, M.D.; Ph.D.
Assistant Prof. & Consultant, Medical
Biochemistry Dept.
College of Medicine, KSU
Metabolic
Pathway
Definition
Site:
Cellular (tissue) and Subcellular
Reactions
Rate-limiting enzyme(s)
Regulatory mechanism(s):
Rapid, short-term:
Allosteric Covalent modification
Slow, long-term:
Induction/repression
Metabolic Pathways of
Glucose
Production and Utilization
Glycogenolysis Hexose interconversion
Gluconeogenesis
Production
Glucose
Utilization
Glycolysis HMP/PPP
Hexose interconversion
Glycogenesis Krebs cycle
Metabolic Pathways of
Glucose:
Catabolic and Anabolic
Catabolic cycles Anabolic cycles
Glycolysis (Mainly) Gluconeogenesis
Krebs (Mainly)
Glycogenolysis Glycogenesis
HMP
Glycogenesis and
Glycogenolysis
Glycogenesis:
Synthesis of glycogen from glucose
Mainly liver and muscle, Cytosol
Glycogenolysis
Degradation of glycogen into glucose
Mainly liver and muscle, Cytosol
Hexose Monophosphate
Pathway (HMP) or
Pentose Phosphate Pathway
(PPP)
Important source for NADPH
Reductive syntheses
Source for metabolically active ribose
Production of nucleotides
For nucleic acids
For co-enzymes
Glycolysis:
Objectives
Major oxidative pathway of glucose
The main reactions of glycolytic pathway
The rate-limiting enzymes/Regulation
ATP production (aerobic/anaerobic)
Pyruvate kinase deficiency hemolytic
anemia
Glycolysis: An
Overview
Glycolysis, the major pathway for glucose
metabolism, occurs in the cytosol of all cells.
It is unique, in that it can function either aerobically
or anaerobically, depending on the availability of
oxygen and intact mitochondria.
It allows tissues to survive in presence or absence of
oxygen, e.g., skeletal muscle.
RBCs, which lack mitochondria, are completely reliant
on glucose as their metabolic fuel, and metabolize it by
anaerobic glycolysis.
Glycolysis
Aerobic Vs Anaerobic
Glycolysis
Aerobic
Glycolysis-1
Hexokinase
Glucokinase
Aerobic
Glycolysis-2
Aerobic
Glycolysis: 3-5
2
2
Aerobic
Glycolysis:
2
6 -10
2
2
Aerobic
Glycolysis-1
Hexokinase:
Most tissues
Hexokinase
Glucokinase: Glucokinase
Hepatocytes
PFK-1 :
Regulation
Aldolase and Triose
Isomerase
Glyceraldeh
yde
2
3-
Phosphate
2
Dehydrogen
ase
For each NADH, 3 ATP will 2
be produced by ETC
in the mitochondria 2
i.e., 6 ATP are produced
2
2
2
Phospho- 2
Substrate-
glycerate Level
Phosphorylation
Kinase 2
2
2
2
Substrate-
2 Level
Phosphorylation
2
Pyruvate
Kinase 2
Substrate-level phosphorylation
Vs. Oxidative phosphorylation
• Phosphorylation is the metabolic reaction of introducing a
phosphate group into an organic molecule.
• Oxidative phosphorylation: The formation of high-energy
phosphate bonds by phosphorylation of ADP to ATP
coupled to the transfer of electrons from reduced
coenzymes to molecular oxygen via the electron transport
chain (ETC); it occurs in the mitochondria.
• Substrate-level phosphorylation: The formation of high-
energy phosphate bonds by phosphorylation of ADP to
ATP (or GDP to GTP) coupled to cleavage of a high-
energy metabolic intermediate (substrate). It may occur in
cytosol or mitochondria
Pyruvate Kinase
Covalent
Modification
Pyruvate Kinase
Deficiency
Hemolytic Anemia
Summary: Regulation of
Glycolysis
Regulatory Enzymes (Irreversible reactions):
Glucokinase/hexokinase
PFK-1
Pyruvate kinase
Regulatory Mechanisms:
Rapid, short-term:
Allosteric
Covalent modifications
Slow, long-term:
Induction/repression
Apply the above mechanisms for each enzyme where applicable
Aerobic Glycolysis: ATP
Production
ATP Consumed:
2 ATP
ATP Produced:
Substrate-level 2X2= 4 ATP
Oxidative-level 2X3= 6 ATP
Total 10 ATP
Net: 10 – 2 = 8 ATP
Take Home Message
Glycolysis is the major oxidative pathway for
glucose
Glycolysis is employed by all tissues
Glycolysis is a tightly-regulated pathway
PFK-1 is the rate-limiting regulatory enzyme
Take Home Message
Glycolysis is mainly a catabolic pathway for
ATP production, But
It has some anabolic features (amphibolic)
Pyruvate kinase deficiency in RBCs results in
hemolytic anemia
THANK YOU
