Carbohydrate Structure and Function & Carbohydrate Metabolism

Learning Outcomes:
•Describe structures & functions of monosaccharides, disaccharides, oligosaccharides and polysaccharides
•Describe catabolism of glucose by glycolysis and Krebs cycle
•Describe Cori cycle
•Describe reactions in gluconeogenesis, glycogenesis, glycogenolysis and pentose phosphate pathway

Carbohydrates are divided into: Carbohydrate Function:

Ø Monosaccharides • Fuel source for cells
Ø Disaccharides • Structural component
Ø Oligosaccharides • Storage component
Ø Polysaccharides • Converted to other
types of organic
Monosaccharides molecules
We can classify
Monosaccharides by:
(i) Number of carbon atoms: Triose, Pentose
(ii) Location of carbonyl group: Aldose sugar,
Ketose sugar
(iii) Linear and ring form
(iv) Phosphorylated sugars
Disaccharides
•2 monosaccharides joined by glycosidic bonds.
»Maltose= glucose + glucose
»Lactose= glucose + galactose
»Sucrose= glucose + fructose

Oligosaccharides Amylose Amylopectin

•contain <20 monosaccharides Amount 15-20% 80-85%
•eg: glycoprotein, glycolipid present in
starch
Polysaccharides Structure Unbranched, Highly
•contain >20 to thousands of monosaccharides linear, helical branched (1,6
•starch in plants (amylose+amylopectin) sructure linkage)
•glycogen in animals’ liver & muscles Linkage α1,4 glycosidic α1,4 glycosidic
•glycogen similar to amylopectin where 1,4 and linkage linkage.
1,6 linked α-glucose present (large, branched) α1,6 glycosidic
•cellulose linkage

Carbohydrate Metabolism
Ø Anabolic pathway: synthesis
Ø Catabolic pathway: breakdown
• Carbohydrate metabolism :
A) Glycolysis
B) Krebs cycle
C) Gluconeogenesis
D) Glycogen synthesis (Glycogenesis)
E) Glycogen degradation (Glycogenolysis)
F) Pentose phosphate pathway

A) GLYCOLYSIS
-occurs in cytosol of cells, regardless oxygen is present or not
-ten reactions in glycolysis
-substrate level phosphorylation
-1 glucose ® 2 pyruvate, 2NADH, 2ATP (nett)

ATP= Adenosine triphosphate

NAD+ = Nicotinamide adenine dinucleotide
= coenzyme, electron acceptor
+
= Vitamin B3 required for synthesis of NAD

reduction
NAD+ NADH + H+
oxidation
After glycolysis, what happens to pyruvate?
Aerobic condition •Pyruvate is oxidized to acetyl-CoA
Pyruvate + CoA +NAD+ --> Acetyl CoA + CO2 + NADH
•Enzyme : pyruvate dehydrogenase
(Coenzyme A = sulfur containing coenzyme derived from vitamin B)

Anaerobic condition •Pyruvate + NADH <--> Lactic acid + NAD+

•Enzyme: Lactate dehydrogenase

Clinical correlation
Pyruvate kinase deficiency
Absolute deficiency Lethal since every cell depends on glycolysis for
ATP
Partial deficiency RBC have insufficient ATP for Na+ pump,
in RBC unable to export electrolytes,
(RBC solely depend unable to maintain osmotic balance (cytosol x
on glycolysis) extracellular compartment),
cell lyse,
=results in haemolytic anaemia

Arsenic poisoning -Arsenic can replace phosphate in reaction catalysed by glyceraldehyde 3-

phosphate dehydrogenase.
-Produce 1-arseno-3-phosphoglycerate instead of
1,3 –diphosphoglycerate.
-unstable, quickly hydrolyses producing 3-phosphoglycerate, even before
ATP can be made. (bypass substrate level phosphorylation reaction
catalysed by phosphoglycerate kinase)

-glycolysis continues, but no ATP is made.

During collection of blood for glucose estimation,

Calcium oxalate used to prevent blood from clotting.
Sodium fluoride used to inhibit in-vitro glycolysis by inhibiting enzyme enolase.

In which is glycolysis always anaerobic?

A.Brain
B.Erythrocytes-doesn’t have mitochondria, cant convert into acetyl-coA
C.Kidney
D.Liver
E.Muscle-anaerobic only when insufficient Oxygen

Cori cycle

Lactate in muscle® liver and converted to glucose by
gluconeogenesis.
Glucose re-enters blood and is used by muscle.
Cycling of lactate between muscle and liver is called Cori cycle.

Glycolitic pathway:
Advantages •Rapid and instant release of energy from glucose
•Doesn’t need oxygen
•Produces pyruvate that can be utilised by other pathways

Disadvantage •Not much ATP produced

•Uses up NAD+, can end up with a shortage of this
B) KREBS CYCLE/ CITRIC ACID CYCLE/ TRICARBOXYLIC ACID CYCLE
• In matrix of mitochondria
• Most important function of Krebs cycle:
Ø Acetyl CoA is further oxidised
Ø Producing energy either directly as ATP or as NADH and FADH2
Ø NADH and FADH2 are oxidised by ETC to produce ATP
(FADH2 oxidised to FAD Flavin adenine dinucleotide)
• Vitamin _____ is required for synthesis of FAD

–Acetyl CoA combines with oxaloacetate to

form citrate

–For each acetyl CoA that enters the cycle:

Ø 3 NADH and 1 FADH2 are produced
Ø 1 ATP is formed by substrate level
phosphorylation
Ø 2 CO2 released

+
1 Acetyl CoA →3 NADH + H + 1 FADH +1 ATP +2 CO
2 2

C) GLUCONEOGENESIS
• synthesis of glucose from non-carbohydrate compounds (lactate, glycerol, amino acids) to maintain
blood glucose level
• occurs in cytosol and mitochondria of cell
• occurs in liver and kidney (NOT MUSCLE)
• different from glycolysis at only 3 steps
D) GLYCOGEN SYNTHESIS and E) GLYCOGEN DEGRADATION
• Glycogen: storage form of carbohydrate
• Occurs in cytosol of liver and muscle cells
• Liver glycogen: to maintain blood glucose
• Muscle glycogen: to provide glucose-6-phosphate for muscle energy requirements
• Muscle does not contain glucose-6-phosphate

Glycogenesis Glycogenolysis
Glycogen synthesis Glycogen degradation
Glucose
hexokinase/glucokinase Glucose
glucose 6-phosphatase

Glucose 6-phosphate Glucose 6-phosphate

phosphoglucomutase
phosphoglucomutase
Glucose 1-phosphate

+ UTP
Glucose 1-phosphate + glucose
UDP-Glucose
glycogen phosphorylase
debranching enzyme
glycogen synthase Glycogen
branching enzyme Glycogen
Glycogen synthesis
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Dr.Gnanajothy Ponnudurai

F) PENTOSE PHOSPHATE PATHWAY/ HEXOSE MONOPHOSPHATE SHUNT

Glycogen degradation
Oxidation of glucose
• Occurs in cytosol of cells But not for energy
• Main function of pentose phosphate pathway: 34
Dr.Gnanajothy Ponnudurai
Ø to production NADPH for synthesis of fatty acid, cholesterol
Ø production of ribose-5-phosphate for nucleotide & nucleic acid synthesis

First step of oxidative phase is

catalysed by glucose-6-phosphate
dehydrogenase, produces NADPH
Metabolism of Fructose and Galactose

Fructose • metabolised mainly in liver.

• converted to fructose 1-phosphate and cleaved to produce dihydroxyacetone
phosphate(DHAP) and glyceraldehyde which is phosphorylated to
glyceraldehyde 3-phosphate.
• DHAP and glyceraldehyde 3-phosphate are intermediates of glycolytic pathway.

Galactose • Galactose is phosphorylated to galactose 1-phosphate which reacts with UDP-glucose.

• The products are glucose 1-phosphate and UDP galactose.
• Glucose 1-phosphate can convert to glucose 6-phosphate and enter glycolytic pathway.

Cori's cycle transfers

Questions A. glucose from muscles to liver
B. lactate from muscles to liver
Name the cellular compartment where the following metabolic C. lactate from liver to muscles
reactions occur: D. pyruvate from liver to muscles
– Glycolysis
– Conversion of pyruvate to lactate Glucose-6-phosphatase is not present in
– Conversion of pyruvate to acetyl CoA A. liver and kidneys
– Krebs cycle B. kidneys and muscles
– Gluconeogenesis C. kidneys and adipose tissue
– Glycogenesis D. muscles and adipose tissue
– Glycogenolysis E. liver and muscle

– Pentose phosphate pathway
Dr.Gnanajothy Ponnudurai

Case: An alcoholic who went on a weekend binge without eating

any food was found to have severe hypoglycemia. The
metabolism of alcohol produces NADH, mainly in the liver. 39
Dr.Gnanajothy Ponnudurai

• As a result of high NADH levels, pyruvate is converted to

Explanation to case
A. Oxaloacetate
B. Acetyl coA • Alanine is transaminated to pyruvate.
C. Phosphoenolpyruvate • The pyruvate/lactate equilibrium greatly favors lactate when
D. Lactate NADH is high.
Pyruvate + NADH « Lactic acid + NAD+
• Hypoglycemia occurred because the metabolism of ethanol • Thus alanine and lactate is prevented from producing glucose.
prevented the production of blood glucose from
A. Glycogen
B. Lactate • Lactate levels are high, resulting in lactic acidosis.
C. Glycerol
D. Alanine
• Glycerol enters gluconeogenesis by forming glycerol 3-
E. Lactate, glycerol and alanine 41phosphate, which is oxidized to dihydroxyacetone phosphate.
Dr.Gnanajothy Ponnudurai

• High NADH prevent this oxidation.

Glycerol 3-phosphate + NAD+ «DHAP + NADH
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Dr.Gnanajothy Ponnudurai