Carbohydrate Metabolism and Biosynthesis

CARBOHYDRATE METABOLISM
AND BIOSYNTHESIS
I. METABOLIC PROPERTIES OF KEY TISSUES
Brain
- Usually neurons use only glucose as energy source
- Since the brain stores only a very small amount of
glycogen, it needs a steady supply of glucose.
Liver
- maintenance of a fairly steady concentration of
glucose in the blood
- This is accomplished through gluconeogenesis and
glycogen synthesis and degradation.
- It is also the site of urea synthesis.
Adipose tissue
- It synthesizes fatty acids and stores them as
triacylglycerols.
- Glucagon activates a hormone-sensitive lipase, which
hydrolizes triacylglycerols yielding glycerol and fatty
acids.
Muscle
- It uses glucose, fatty acids, ketone bodies and
aminoacids as energy source.
- It also contains a reserve of creatine-phosphate, a
compound with a high phosphate-transfer potential
that is able to phosphorilate ADP to ATP.
Kidney
- It can perform gluconeogenesis and release
glucose into the bloodstream
- It is also responsible for the excretion of urea,
electrolytes, etc.
Hormone control
- mainly affected through the action of two
hormones synthesized by the pancreas: insulin
and glucagon.
- Insulin is released by the pancreas when blood
glucose levels are high, i.e., after a meal.
II.FRUCTOSE METABOLISM
Organs that metabolize fructose:
1.Liver
2.Kidney
3.Intestine
4.adipose tissue
II.FRUCTOSE METABOLISM
Enzymes involved in fructose metabolism:

1. hexokinase – can phosphorylate fructose to
fructose – 6 – phosphate or
glucose to glucose - 6 – phosphate
2. fructokinase – can phosphorylate fructose to
fructose – 6 – phosphate
Deficiencies involved:
1 Hereditary fructokinase deficiency
( fructosuria )
2. Glucosuria
3. Fructose 1 – P Adolase Deficiency
4. Hypoglycemia (low serum glucose levels)
III. GALACTOSE METABOLISM
Organs that metabolize galactose
1. Liver
2. Erythrocytes
Gliucose-1-P + UTP ------ UDP Glucose + PP1
Enzyme involving galactose metabolism

1. Galactokinase- phosphorylates galactose to galactose-1-P
2. Uridyl Transferase – removes glucose 1-P from UDP glucose and create
UDP galactose
2-Uridyl Transferases
a. galactose 1-P
b. hexose 1-P uridyl transferase
3. UDP glucose epimerase – changes the OH configuration at carbon 4 of UDP
galactose to yield UDP glucose.
GLUCONEOGENESIS
GLUCONEOGENESIS
 Gluconeogenesis is the synthesis of
glucose from non-carbohydrate
precursors.
 Gluconeogenesis is not the reversal of
glycolysis.
 The bypass reactions make the synthesis
of glucose thermodynamically feasible.
 Gluconeogenesis and glycolysis are
reciprocally regulated.
INTRODUCTION TO THE
GLUCONEOGENESIS PATHWAY
Main Purpose - to synthesize glucose from
non-carbohydrate precursors. This process
occurs mainly in the liver and kidney.
Major function - to provide glucose for the

brain and muscle. The main precursors
used by this pathway are lactate, alanine,
and glycerol.
Gluconeogenesis Pathways
Three irreversible reactions that must be
bypassed in gluconeogenesis
pyruvate kinase
 phosphofructokinase-1(PFK-1)
 hexokinase/glucokinase
Bypass 1-
Pyruvate to Phosphoenolpyruvate (PEP)
2 mitochondrial enzymes involved:

 pyruvate carboxylase (PC)
 PEP carboxykinase (PEPCK)
The net result of the PC and PEPCK reactions is:
Pyruvate + ATP + GTP + H2O ---> PEP + ADP

+ GDP + Pi + 2H+
Bypass 2-
Fructose-1,6-bisphosphate to Fructose-6-
phosphate
 The reverse of the rate limiting step of

glycolysis.
 The reaction, a simple hydrolysis, is catalyzed by
fructose-1,6-bisphosphatase (F1,6BPase)
 Like the regulation of glycolysis occurring at the
PFK-1 reaction, the F1,6BPase reaction is a
major point of control of gluconeogenesis
Bypass 3-
Glucose-6-phosphate (G6P) to Glucose

(or Glycogen), Bypass 3
 G6P is converted to glucose through the

action of glucose-6-phosphatase G6Pase).
This reaction is also a simple hydrolysis
reaction like that of F1,6BPase.
Substrates for Gluconeogenesis
 Lactate
 Pyruvate
 Amino Acids
 Glycerol
 Propionate
 Lactate -a predominate source of

carbon atoms for glucose synthesis
by gluconeogenesis.
During anaerobic glycolysis in skeletal

muscle, pyruvate is reduced to lactate by
lactate dehydrogenase (LDH). This
reaction serves two critical functions
during anaerobic glycolysis.
Critical functions of pyruvate reduction to lactate
1. In the direction of lactate formation, the LDH reaction

requires NADH and yields NAD+ which is then available
for use by the glyceraldehyde-3-phosphate
dehydrogenase reaction of glycolysis.
2. The lactate produced by the LDH reaction is released to

the blood stream and transported to the liver where it is
converted to glucose. The glucose is then returned to the
blood for use by muscle as an energy source and to
replenish glycogen stores. This cycle is termed the Cori
cycle.
Lactate
Lactate
The Cori cycle involves the utilization of

lactate, produced by glycolysis in non-
hepatic tissues, (such as muscle and
erythrocytes) as a carbon source for
hepatic gluconeogenesis.
In this way the liver can convert the

anaerobic byproduct of glycolysis, lactate,
back into more glucose for reuse by non-
hepatic tissues.
 Pyruvate, generated in muscle and other

peripheral tissues, can be transaminated
to alanine which is returned to the liver for
gluconeogenesis. The transamination
reaction requires an a-amino acid as donor
of the amino group, generating an a-keto
acid in the process. This pathway is
termed the glucose-alanine cycle.
Pyruvate
Pyruvate
 The glucose-alanine cycle is
used primarily as a mechanism
for skeletal muscle to eliminate
nitrogen while replenishing its
energy supply.
Amino Acids
 All 20 of the amino acids, excepting leucine and
lysine, can be degraded to TCA cycle
intermediates.
 Carbon skeletons of the amino acids are to be
converted to those in oxaloacetate and
subsequently into pyruvate .
 The pyruvate thus formed can be utilized by the
gluconeogenic pathway.
 Catabolism of muscle proteins to amino acids
contributes the major source of carbon for
maintenance of blood glucose levels
Glycerol
 The glycerol backbone of lipids
can be used for gluconeogenesis.
Propionate
 The utilization of propionate in
gluconeogenesis only has
quantitative significance in
ruminants
Regulation of Gluconeogenesis
 The regulation of gluconeogenesis will be
in direct contrast to the regulation of
glycolysis.
 In general, negative effectors of glycolysis
are positive effectors of gluconeogenesis.
 Gluconeogenesis cannot be considered to
be simply a reverse process of glycolysis ,
as the three irreversible steps in glycolysis
are bypassed in gluconeogenesis.
 This is done to ensure that glycolysis and
gluconeogenesis are not operating at the
same time in the cell, making it a
futile cycle.
 Glycolysis and gluconeogenesis follow
reciprocal regulation, , that is, cellular
conditions, which inhibit glycolysis, may in
turn activate gluconeogenesis.
 The majority of the enzymes responsible for
gluconeogenesis are found in the cytoplasm;
exceptions:
 mitochondrial pyruvate carboxylase
 mitochondrial phosphoenolpyruvate carboxykinase
which are located in the mitochondria.
 The rate of gluconeogenesis is ultimately
controlled by fructose-1,6-bisphosphatase, which
is also regulated through signal tranduction by
cAMP and its phosphorylation.
GLYCOGENOLYSIS &
GLYCOGENESIS
 The breaking down, or catabolism, of the
polysaccharide glycogen into molecules of
the sugar glucose and molecules of
glucose 1-phosphate within the body by
enzymes
GLUCOSE
 Glucagon is released from the pancreas in
response to low blood glucose.
 epinephrine is released in response to a

threat or stress.
Glycogenesis
 Glycogenesis is the formation of glycogen
from glucose. Glycogen is synthesized
depending on the demand for glucose and
ATP (energy).
PENTOSE PHOSPHATE
PATHWAY
 also called Phosphogluconate Pathway, or
Hexose Monophosphate Shunt [HMP
shunt])
 a process that serves to generate NADPH

and the synthesis of pentose (5-carbon)
sugars.
PHASES
Oxidative phase
 Non-oxidative phase

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CARBOHYDRATE METABOLISM

Organs that metabolize fructose:

Enzymes involved in fructose metabolism:

Gliucose-1-P + UTP ------ UDP Glucose + PP1

Enzyme involving galactose metabolism

Major function - to provide glucose for the

2 mitochondrial enzymes involved:

The net result of the PC and PEPCK reactions is:

Pyruvate + ATP + GTP + H2O ---> PEP + ADP

 The reverse of the rate limiting step of

Glucose-6-phosphate (G6P) to Glucose

 G6P is converted to glucose through the

 Lactate -a predominate source of

During anaerobic glycolysis in skeletal

Critical functions of pyruvate reduction to lactate

1. In the direction of lactate formation, the LDH reaction

2. The lactate produced by the LDH reaction is released to

The Cori cycle involves the utilization of

In this way the liver can convert the

 Pyruvate, generated in muscle and other

 epinephrine is released in response to a

 a process that serves to generate NADPH

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