CARBOHYDRATE METABOLISM Lecture Notes 2022
CARBOHYDRATE METABOLISM Lecture Notes 2022
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• simple sugars
Carbohydrates can be divided into four major • consist of a single • Consists of two • Short chains of 2 – • Consists of more
polyhydroxy monosaccharides 10 than 10
classes: aldehyde or monosaccharide monosaccharide
polyhydroxy units unites
1) Monosaccharides ketone
• carbohydrate that • Can be hydrolyzed • Will yield 2 – 10 • Will yield more
cannot be into two monosaccharides than 10
2) Disaccharides hydrolyzed any monosaccharides when completely monosaccharides
further hydrolyzed when completely
hydrolysed
3) Oligosaccharides • Eg. glucose, • Eg. Lactose, • Eg. Raffinose
galactose, fructose sucrose, maltose • Eg. Amylose,
4) Polysaccharides amylopect,
glycogen,
cellulose,
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Amylose
amylose
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Preparatory Phase
• The first five steps of glycolysis
• glucose is phosphorylated at the expense
• The breakdown of glucose via glycolysis is the of two ATP molecules
• glyceraldehyde 3-phosphate (and
sole source of metabolic energy for many dihydroxyacetone phosphate) are
generated
animal tissues and cell types (e.g. RBCs, renal • dihydroxy acetone can be converted to
glyceraldehyde 3-phosphate by triose
medulla, brain and sperm) phosphate isomerase
arsenate
Phosphoglycerate kinase
1-arseno-3-phosphoglycerate
3-Phosphoglycerate + HEAT
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Pyruvate
1 Glucose
2 ATP
2 ADP
2 Glyceraldehyde 3-phosphate
4 ADP 2 NAD+
+ 4 ATP 2 NADH
2 Pyruvate
Pyruvate Pyruvate
NAD+ NAD+ NADH
Pyruvate Pyruvate
dehydrogenase dehydrogenase Lactate
complex complex dehydrogenase
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Fates of Pyruvate:
Glucose Entry into Cells/Tissues
Pyruvate Tissue Location Function
NAD+ NADH Pyruvate Facilitative bidirectional transporters
Pyruvate
Lactate Brain, kidney, colon, placenta,
dehydrogenase
dehydrogenase GLUT 1 Uptake of glucose
complex Pyruvate erythrocyte
decarboxylase
NADH NAD+ Liver, pancreatic B cell, small
GLUT 2 Rapid uptake and release of glucose
intestine, kidney
Acetyl-CoA Lactate Acetaldehyde
GLUT 3 Brain, kidney, placenta Uptake of glucose
Heart and skeletal muscle,
GLUT 4 Insulin-stimulated uptake of glucose
adipose tissue
Alcohol
dehydrogenase GLUT 5 Small intestine Absorption of glucose
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• The pentose phosphate pathway is active; • Glycogenesis also occurs in these cells;
produces NADPH needed for reduction significant quantities of glycogen are made
reactions which are stored for later use
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GLYCOGEN
GLYCOGENESIS
UTP
Branching
enzyme
Glycogen
synthase
Glycogen primer
UDP-Glucose
2Pi PPi
Glycogenin
• The pre-existing glycogen molecule, or “glycogen primer,” is UDP-glucose
pyrophosphorylase
UTP UTP
Branching Branching
enzyme enzyme
Glycogen Glycogen
cAMP synthase
cAMP synthase
GLUCOSE GLUCOSE
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INSULIN GLYCOGEN
CARBOHYDRATE METABOLISM
UTP
Glycogen
Branching
enzyme GLYCOGEN
cAMP synthase
UDP-Glucose
Glycogen primer Glycogenolysis Glycogenesis
2Pi PPi
UDP-glucose
pyrophosphorylase
Glycogenin GLUCOSE
Glucose 6-phosphate
Mg2+ hexokinase/
glucokinase
PYRUVATE
GLUCOSE
GLYCOGENOLYSIS
GLYCOGENOLYSIS GLYCOGEN
Pi
phosphoglumutase
Glucose 6-phosphate
• Glycogenolysis is a separate pathway, NOT a
Glucose 6-
reverse of glycogenesis phosphatase
GLUCOSE
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GLYCOGENOLYSIS GLYCOGENOLYSIS
GLYCOGEN GLYCOGEN
Pi Pi
Glucose 6- Glucose 6-
phosphatase phosphatase INSULIN
GLUCOSE GLUCOSE
GLUCAGON GLUCAGON
EPINEPHRINE EPINEPHRINE
*Glucose-6-phosphatase is absent from brain and muscle cells *Glucose-6-phosphatase is absent from brain and muscle cells
characterized by deposition of an abnormal Type II Pompe’s disease Deficiency of Fatal, accumulation of glycogen
lysosomal α-1-4- in lysosomes, heart failure.
type or quantity of glycogen in the tissues glucosidase
and 1-6-
glucosidase
• Some recently discovered deficiencies are of
Adenylyl kinase and cAMP-dependent Type III Limit dextrinosis,
Forbes’ or Cori’s
Absence of
debranching
Accumulation of a characteristic
branched polysaccharide
protein kinase disease enzyme
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Glucose
hexokinase
Fructose 6-phospate
• In humans, gluconeogenesis enables the Phosphofructokinase-1
after all dietary glucose has been absorbed Dihydroxyacetone phosphate Glyceraldehyde 3-phosphate
and completely oxidized and glucose stored
as glycogen has been used up 1,3-Biphosphoglycerate
3-Phosphoglycerate
• Important precursors of glucose in animals
are: lactate, pyruvate, glycerol and amino 2-Phosphoglycerate
Pyruvate kinase
Pyruvate
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Glucose
hexokinase
3 irreversible (i.e.
Fructose 6-phospate cannot be reversed in
• Gluconeogenesis occurs largely in the liver Phosphofructokinase-1 gluconeogenesis)
(and to a smaller extent in the renal cortex) Fructose 1, 6-phospate
reactions of GLYCOLYSIS
Pyruvate kinase
Pyruvate
Glucose Glucose
Gluconeogenesis: 1st Bypass
Bypass 3 Bypass 3
Glucose 6-phospate • In Glucose 6-phospate
GLUCONEOGENESIS,
Fructose 6-phospate these 3 reactions are Fructose 6-phospate
Bypass 2
‘bypassed’ by a Bypass 2
Fructose 1, 6-phospate
separate set of Fructose 1, 6-phospate
enzymes
• The bypass reactions
Dihydroxyacetone phosphate Glyceraldehyde 3-phosphate Dihydroxyacetone phosphate Glyceraldehyde 3-phosphate
are highly exergonic
and cannot be
1,3-Biphosphoglycerate 1,3-Biphosphoglycerate
reversed in glycolysis
3-Phosphoglycerate 3-Phosphoglycerate
2-Phosphoglycerate 2-Phosphoglycerate
Bypass 1 Bypass 1
Pyruvate Pyruvate
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Glucose
Gluconeogenesis: 1st Bypass Glucose
Gluconeogenesis: 2nd Bypass
Bypass 3
Glucose 6-phospate Glucose 6-phospate
malate export to
3-Phosphoglycerate cytosol is not really 3-Phosphoglycerate
necessary
2-Phosphoglycerate 2-Phosphoglycerate
Glucose
Gluconeogenesis: 3rd Bypass
Mg2+ Glucose 6-phosphatase
Glucose 6-phospate
Gluconeogenesis
• Glucose 6-phosphate is
Fructose 6-phospate
dephosphorylated by • The intermediates in the TCA cycle; citrate,
Glucose 6-phosphatase isocitrate, α-ketoglutarate, succinyl CoA,
Fructose 1, 6-phospate
to yield free glucose
succinate, fumurate, and malate; all can be
Dihydroxyacetone phosphate Glyceraldehyde 3-phosphate
• Glucose 6-phosphatase
oxidised to pyruvate
1,3-Biphosphoglycerate
is Mg2+-dependent and
is found in hepatocytes
3-Phosphoglycerate and renal cells but NOT • Thus the intermediates of the TCA cycle can all
present in muscles or be used to synthesise glucose via the
2-Phosphoglycerate brain gluconeogenesis pathway
Phosphoenolpyruvate (PEP)
Pyruvate
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Glucose
Gluconeogenesis
Gluconeogenesis Summary:
Glucose 6-phospate
Fructose 6-phospate
Glucose
Fructose 1, 6-phospate
1,3-Biphosphoglycerate Pyruvate
3-Phosphoglycerate
citrate, isocitrate,
2-Phosphoglycerate
α-ketoglutarate,
succinyl CoA,
succinate,
Phosphoenolpyruvate (PEP) Oxaloacetate Lactate
fumurate, malate Amino acids
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• The capacity of the tubular system to • Glucosuria occurs when the venous blood
reabsorb glucose is limited to a rate of glucose concentration exceeds the renal
about 350 mg/min threshold for glucose (9.5–10.0 mmol/L)
• During pregnancy, foetal glucose • Premature and low birth-weight babies have
consumption increases with the risk of little adipose tissue
maternal and possibly foetal hypoglycaemia
• Therefore they are not able to generate
alternative fuels such as free fatty acids or
• Risk of hypoglycaemia is greater at this time ketone bodies during the transition from foetal
especially during long intervals between dependency to the free-living state
meals or at night
• Thus premature and low birth-weight babies
are more susceptible to hypoglycaemia
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GLYCOGEN GLYCOGEN
PYRUVATE PYRUVATE
Glucose 6- NADP+
• An alternate route for glucose metabolism phosphate
dehydrogenase
Phosphogluconolactone
Glyceraldehyde 3-phosphate Glycolysis
1. NADPH + H+
2. Ribose 5’-phosphate Ribose 5-phosphate
de novo synthesis
PRPP
of nucleotides
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The Pentose Phosphate Pathway Role of the pentose phosphate pathway in the Glutathione
peroxidase reaction of erythrocytes
• Oxidation here is achieved by dehydrogenation
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STUDY QUESTIONS
REFERENCES
• Define metabolism, anabolism and catabolism.
• Murray RK, Granner DK, Mayes, Rodwell VW. Harper’s Biochemistry • What is glycolysis? What is the significance of glycolysis?
24th Edition 1996 • What is aerobic glycolysis? What is anaerobic glycolysis?
• Describe the glycolysis in erythrocytes. What is 2,3 BPG?
• Delvin TM. Textbook of Biochemistry with Clinical Correlations 4th • List the components of the pyruvate dehydrogenase complex. What
Edition 2001 coenzymes and B vitamins are needed by this complex?
• What is the Citric Acid Cycle? What is its significance?
• Nelson DL and Cox MM. Lehninger Principles of Biochemistry • Describe glycogenesis and glycogenolysis.
3rd Edition, 2000, Worth Publishers, New York. • How are glycogenesis and glycogenolysis pathways regulated?
• What is gluconeogenesis?
• Koolman J and Roehm KH. Colour Atlas of Biochemistry 2nd Edition • What reactions of the glycolysis pathways are not reversed in
2005 gluconeogenesis?
STUDY QUESTIONS
• What is the Cori cycle? What is the significance of the Cori Cycle?
• What is the Alanine Cycle? What is the significance of Alanine
Cycle?
• What is the significance of the Pentose Phosphate Pathway?
• What is the significance of the Uronic acid pathway?
• What disease conditions may occur as a result of defects in
glycolysis?
• What disease conditions may occur as a result of defects in
glycogenesis?
• What disease conditions may occur as a result of defects in
glycogenolysis?
• What disease conditions may occur as a result of defects in
glyconeogenesis?
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