Carbohydrate Metabolism
Metabolism
Metabolism is the sum total of
all chemical reactions occurring in the living body. In other words Metabolism
is a term that is used to describe all chemical reactions involved in
maintaining the living state of the cells and the organism. Metabolism can be
conveniently divided into two categories:
·
Catabolism - the breakdown of molecules to
obtain energy
·
Anabolism - the synthesis of all compounds
needed by the cells
Metabolism is closely linked to nutrition
and the availability of nutrients. Bioenergetics is a term which describes the
biochemical or metabolic pathways by which the cell ultimately obtains energy.
Energy formation is one of the vital components of metabolism. So, metabolism
performs 4 functions 1. Obtain energy for the cell. 2. Convert nutrients into macromolecules. 3. Assemble macromolecules into cellular
structures. 4. Degrade
macromolecules as required for biological function.
Difference between catabolism
and anabolism.
|
Anabolism: |
Catabolism: |
|
1. It is a constructive phase of
metabolism. |
1. It is a destructive phase of metabolism. |
|
2. In anabolism, complex molecules (e.g.
proteins) are synthesized from simple molecules (Amino acids). |
2. In catabolism, complex molecules (e.g.
Glycogen) are broken down into simple molecules (glucose). |
|
3. It is an energy (ATP) requiring process. |
3. It is an energy (ATP) releasing process. |
|
4. e.g. Protein synthesis, Glycogen
synthesis. |
4. E.g. Glycogenolysis, Glycolysis. |
Nutrition is the key to metabolism. The pathways of
metabolism rely upon nutrients that they break down in order to produce energy.
This energy, in turn, is required by the body to synthesize new proteins, nucleic
acids (DNA, RNA), etc. Anabolism is a process in which the liver creates new
proteins from digested nutrients, while catabolism involves the breaking down
of proteins into essential amino acids. Both are vital to the body's
metabolism and maintaining healthy cell function
6.1 Carbohydrates in metabolism
Carbohydrate metabolism refers to the
biochemical processes that the body uses to break down carbohydrates (like
sugars and starches) into usable energy. This energy is mainly in the form of ATP
(adenosine triphosphate),
which powers cellular activities.
Major steps and flow in Carbohydrate
Metabolism
1. Digestion
of Carbohydrates
o
Begins in the mouth (salivary amylase) and
continues in the small intestine.
o
Complex carbs (like starch) → broken down into
simple sugars (mainly glucose).
2. Absorption
and Transport
o
Glucose is absorbed into the bloodstream and
transported to cells.
3. Glycolysis
(in cytoplasm)
o
Glucose (6 carbon) → broken into 2 molecules of
pyruvate (3 carbon).
o
Produces a small amount of ATP and NADH.
o
Occurs with or without oxygen.
4. Aerobic
Respiration (with oxygen)
o
Pyruvate enters mitochondria →
converted to Acetyl-CoA.
o
Goes through the Krebs Cycle
(Citric Acid Cycle) and Electron Transport Chain (ETC).
o
Produces large amounts of ATP, CO₂, and
water.
5. Anaerobic
Respiration (without oxygen)
o
In the absence of oxygen, pyruvate → lactic
acid (in animals) or ethanol (in yeast).
o
Produces less ATP.
6. Glycogenesis
o
Excess glucose → stored as glycogen
in the liver and muscles.
7. Glycogenolysis
o
When needed, glycogen is broken back down to
glucose.
8. Gluconeogenesis
o
Formation of glucose from
non-carbohydrate sources (like amino acids or glycerol) when glucose
levels are low.
Major pathways of
carbohydrate metabolism
The important pathways of carbohydrate metabolism are listed
1. Glycolysis (Embden-Meyerhof Parnas pathway): The oxidation
of glucose to pyruvate and lactate.
2. Citric acid cycle (Krebs cycle or tricarboxylic acid
cycle): The oxidation of acetyl-CoA to
CO2. The Krebs cycle is the final common oxidative pathway for carbohydrates, fats, or amino acids, through acetyl-CoA.
3. Gluconeogenesis : The synthesis of glucose from
non-carbohydrate precursors( e.9. amino acids, glycerol etc.).
4. Glycogenesis: The formation of glycogen from glucose.
5. Glycogenolysis: The breakdown of glycogen to glucose
Digestion is the mechanical and chemical breakdown of food into smaller components that can be easily absorbed into the bloodstream. It is a form of catabolism, breaking down large food molecules into smaller ones. The digestion process involves several stages, starting in the mouth and continuing through the gastrointestinal tract.
Carbohydrates are made up of
sugars known as saccharides. Most carbohydrate foods contain many saccharides
linked together, known as polysaccharides. Carbohydrate digestion begins in the
mouth and is complete when the polysaccharides are broken down into single
sugars, or monosaccharides, which the body can absorb.
In the Mouth:
Carbohydrate digestion begins in the mouth, where both mechanical and chemical processes take place. Mastication (chewing) breaks down food into smaller pieces, increasing the surface area for enzyme action. At the same time, saliva, secreted by the salivary glands, moistens the food and makes it easier to swallow. Saliva contains the enzyme salivary amylase, which initiates the chemical digestion of carbohydrates by breaking down complex polysaccharides like starch into smaller sugar molecules such as maltose. After thorough mixing and partial digestion, the food becomes a soft, moist mass called a bolus, which is then swallowed and transported to the stomach via the esophagus through a series of muscular contractions known as peristalsis.
In the stomach:
Once the bolus reaches the
stomach, it mixes with gastric juices, forming a
semi-liquid substance called chyme. The stomach
provides an acidic environment due to
the secretion of hydrochloric acid (HCl), which halts carbohydrate
digestion by inactivating salivary amylase.
There is no significant chemical digestion of carbohydrates that occurs here.
In the
Pancreas and Small Intestine:
After leaving the stomach, the chyme
enters the duodenum, the first part
of the small intestine. Here, the pancreas
secretes pancreatic amylase, an
enzyme that continues breaking down complex carbohydrates (polysaccharides)
into simpler disaccharides like maltose. The lining of the small intestine,
known as the brush border, produces
specific enzymes—maltase, sucrase, and lactase—which
further break down these disaccharides into monosaccharides
such as glucose, fructose, and galactose. These monosaccharides are then ready
for absorption into the bloodstream, completing the process of carbohydrate
digestion.
Absorption
Monosaccharides like glucose, fructose, and
galactose are absorbed through the intestinal lining into the
bloodstream. This absorption mainly occurs in the jejunum and ileum
sections of the small intestine. Glucose and galactose are absorbed by active
transport, which requires energy and specific carrier proteins, while
fructose is absorbed by facilitated diffusion without energy
use. After absorption, these monosaccharides enter the capillaries
of the intestinal villi and are transported via the hepatic portal vein
to the liver, where they are either converted to glucose for
energy or stored as glycogen for future use.
Undigested Carbohydrates: Carbohydrates that are not digested and absorbed in the small intestine reach the colon.Intestinal bacteria partially break down these carbohydrates. Dietary fiber, which cannot be digested by human enzymes, is either fermented by bacteria or excreted with feces.
In the Large
intestine (Colon)
Carbohydrates that were not digested and absorbed by the small intestine reach the colon, where they are partly broken down by intestinal bacteria. Fiber, which cannot be digested like other carbohydrates, is excreted with feces or partly digested by the intestinal bacteria.
Glucose and galactose are
absorbed in the small intestine by secondary active transport.
They enter the intestinal cell (enterocyte) by riding together with sodium ions
(Na⁺) through a special “door” called SGLT1 (Sodium-Glucose
Linked Transporter 1). This process does not directly use energy from ATP, but
it depends on a sodium gradient, which is created and maintained by another
pump, the Na⁺/K⁺-ATPase on the other side of the cell.
Fructose, on the other hand, uses a different method called facilitated
diffusion. It passes into the cell through a separate transporter, GLUT5,
without needing sodium or energy, simply moving from an area of higher
concentration to lower concentration. Once inside the cell, all three sugars
leave through GLUT2 on the opposite side and enter the blood
for transport to the liver.
Mechanisms of Absorption
|
Sugar |
Transport
Mechanism |
Carrier Protein |
Energy
Requirement |
|
Glucose |
Secondary active transport with Na⁺ |
SGLT1 (Sodium-Glucose Linked Transporter 1) |
Yes (indirect, uses Na⁺ gradient maintained by
Na⁺/K⁺-ATPase) |
|
Galactose |
Same as glucose |
SGLT1 |
Yes |
|
Fructose |
Facilitated diffusion |
GLUT5 |
No, it just moves down its concentration gradient
(facilitated diffusion). |
Fate of Glucose After Absorption
1. Immediate
Energy Production
o Cells
take up glucose and break it down via glycolysis
→ Krebs cycle → oxidative
phosphorylation to produce ATP.
o This
fuels activities like muscle contraction, nerve signaling, and cell metabolism.
2. Storage
as Glycogen
o In
the liver and muscles,
excess glucose is stored as glycogen (glycogenesis).
o This
stored glycogen can be broken down later when blood sugar drops
(glycogenolysis).
3. Conversion
to Fat
o If
glycogen stores are full and energy intake is still high, glucose can be
converted into fatty acids and stored as triglycerides
in adipose tissue (lipogenesis).
4. Supply
to Other Organs
o The
liver releases glucose into the blood to maintain normal
blood sugar for organs like the brain and red blood cells,
which rely almost entirely on glucose for energy.
5. Formation
of Other Molecules
o Glucose
can be used to make non-essential amino acids,
nucleotides (for DNA/RNA), and other important biomolecules.
Intermediary metabolism
of carbohydrates
Intermediary metabolism of carbohydrates
means the series of chemical reactions inside the body that process carbohydrates
(mainly glucose) after digestion and absorption, to either produce energy,
store it, or convert it into other substances.
It’s called “intermediary”
because these reactions happen in between (intermediate stage) — after food is
broken down, but before final products like ATP, fats, or proteins are made.
Main Pathways with
Examples
1.
Glycolysis
o Glucose
is broken down into pyruvate, producing ATP (energy) and NADH.
o Example:
When you run, muscle cells use glycolysis to quickly make energy.
2.
Glycogenesis
o Excess
glucose is stored as glycogen in the liver and muscles.
o Example:
After eating rice, your liver stores extra glucose as glycogen.
3.
Glycogenolysis
o Stored
glycogen is broken back into glucose when blood sugar drops.
o Example:
Between meals, liver glycogen is broken down to keep blood glucose normal.
4.
Gluconeogenesis
o New
glucose is made from non-carbohydrate sources (like amino acids, glycerol).
o Example:
During fasting, your body makes glucose from muscle proteins.
5.
Pentose Phosphate Pathway (HMP Shunt)
o Glucose
is used to produce NADPH (for fat synthesis) and ribose-5-phosphate (for
DNA/RNA).
o Example:
Rapidly dividing cells use this pathway to make DNA building blocks.
6.
Conversion to Fat (Lipogenesis)
o If
glycogen stores are full, glucose is converted into fatty acids and stored as
fat.
Glycolysis
Glycolysis is sequence of ten enzyme-catalyzed reactions that
converts glucose, into pyruvate. The free energy released
in this process is used to form the high-energy compounds ATP (adenosine triphosphate)
and NADH (reduced
nicotinamide adenine dinucleotide) . So
simpy the Glycolytic pathway describes the oxidation of glucose to
pyruvate with the generation of ATP and NADH. The
glycolysis is also called as the Embden–Meyerhof–Parnas
(EMP pathway), which was discovered by Gustav Embden, Otto Meyerhof, and Jakub Karol Parnas.
The entire glycolysis pathway
can be separated into two phases
·
The Preparatory
Phase – in which ATP is consumed and is hence also known as the investment
phase. This phase is also called glucose activation phase. In the
preparatory phase of glycolysis, two molecules of ATP are invested and the hexose
chain is cleaved into two triose phosphates. During this, phosphorylation of
glucose and it’s conversion to glyceraldehyde-3-phosphate take place
·
The Pay Off Phase –
in which ATP is produced. This phase is also called energy extraction
phase. During this phase, conversion of glyceraldehyde-3-phophate to
pyruvate and the coupled formation of ATP take place.
The
overall reaction of glycolysis which occurs in the cytoplasm
is represented simply as:
C6H12O6 + 2 NAD+ + 2 ADP + 2 P —–> 2 pyruvic acid, (CH3(C=O)COOH
+ 2 ATP + 2 NADH + 2 H+
Steps involved
in Glycolysis
1. Phosphorylation of Glucose
Glucose+ATP→Glucose-6-phosphate+ADP
Glucose
is phosphorylated to form glucose-6-phosphate. The reaction is catalysed by the
specific enzyme glucokinase in liver cells and by non specific
enzyme hexokinase in liver and extrahepatic tissue. The enzyme
splits the ATP into ADP, and the Pi is added onto the glucose.
2 : Isomerization of Glucose-6-Phsphate to
Fructose-6-Phosphate
Glucose-6-phosphate → Fructose-6-phosphate
Glucose-6-phosphate is isomerised to
fructose-6-phosphate by phosphohexose isomerase.. This reaction
involves an aldose-ketose isomerisastion catalysed by phosphohexose isomerase.
There is opening of the glucopyranose ring of glucose-6-phosphate to a linear
structure which then changes to the furanose ring structure of
fructose-6-phosphate.
3 : Phosphorylation of F-6-P to Fructose 1,6-Bisphosphate
Fructose-6-phosphate +ATP→ Fructose-1,6-bisphosphate +ADP
- Fructose-6-phosphate
is further phosphorylated to fructose 1,6-bisphosphate.
- The enzyme
is phosphofructokinase-1. It catalyses the transfer of a
phosphate group from ATP to fructose-6-phosphate.
- The reaction
is irreversible.
- One ATP is
utilised for phosphorylation.
- Phosphofructokinase-1
is the key enzyme in glycolysis which regulates breakdown
of glucose.
4 : Cleavage of Fructose 1,6-Biphosphate
.Fructose-1,6-bisphosphate → Glyceraldehyde-3-phosphate + Dihydroxyacetone
phosphate
- The 6 carbon
fructose-1,6-bisphosphate is cleaved into two 3 carbon units; one
glyceraldehyde-3-phosphate (GAP) and another molecule of dihydroxy acetone
phosphate (DHAP).
- The enzyme
which catalyses the reaction is aldolase. Since the backward
reaction is an aldol condensation, the enzyme is called aldolase.
- The reaction
is reversible.
Step 5 : Interconversion of the Triose Phosphates
Dihydroxyacetone phosphate → Glyceraldehyde-3-phosphate
- GAP is on
the direct pathway of glycolysis, whereas DHAP is not. Hence Triose-phosphate
isomerase converts DHAP into GAP useful for generating ATP. Thus
net result
- is that
glucose is now cleaved into 2 molecules of glyceraldehyde-3-phosphate.
- This
reaction is rapid and reversible.
Step 6 : Oxidative phosphorylation of GAP to
1,3-Bisphosphoglycerate
Glyceraldehyde-3-phosphate + NAD⁺ + Pi → 1,3-bisphosphoglycerate + NADH
+ H⁺
- The first
step in the payoff phase is the oxidation of glyceraldehyde 3-phosphate to
1,3-bisphosphoglycerate.
- This
reaction is catalyzed by glyceraldehyde 3-phosphate dehydrogenase.
- It is the
energy-yielding reaction. Reactions of this type in which an aldehyde
group is oxidised to an acid are accompanied by liberation of large
amounts of potentially useful energy. During this reaction, NAD+ is
reduced to NADH.
- This is a
reversible reaction.
Step 7 : Conversion of 1,3-Biphosphoglycerate to
3-Phosphoglycerate
1,3-bisphosphoglycerate
+ ADP → 3-phosphoglycerate + ATP
- The
enzyme phosphoglycerate kinase transfers the high-energy
phosphoryl group from the carboxyl group of 1,3-bisphosphoglycerate to
ADP, forming ATP and 3-phosphoglycerate.
- This is a
unique example where ATP can be produced at substrate level without
participating in electron transport chain. This type of reaction where ATP
is formed at substrate level is called as Substrate level phosphorylation.
Step 8 : Conversion of 3-Phosphoglycerate to
2-Phosphoglycerate
3-phosphoglycerate → 2-phosphoglycerate
- 3-phospho
glycerate is isomerized to 2-phospho glycerate by shifting the phosphate
group from 3rd to 2nd carbon atom.
- The enzyme
is phosphogluco mutase.
- This is a
readily reversible reaction.
- Mg2+ is
essential for this reaction.
Step 9 : Dehydration of 2-Phosphoglycerate to
Phosphoenolpyruvate
2-phosphoglycerate → Phosphoenolpyruvate (PEP) + H₂O
- 2-phosphoglycerate
is converted to phosphoenol pyruvate by the enzyme enolase.
- One water
molecule is removed.
- A high
energy phosphate bond is produced. The reaction is reversible.
- Enolase
requires Mg++.
Step 10 : Conversion of Phosphoenol Pyruvate to Pyruvate
Phosphoenolpyruvate + ADP → Pyruvate + ATP
- Phosphoenol
pyruvate (PEP) is dephosphorylated to pyruvate, by pyruvate kinase.
- First PEP is
made into a transient intermediary of enol pyruvate; which is
spontaneously isomerized into keto pyruvate, the stable form of pyruvate.
- One mole of
ATP is generated during this reaction. This is again an example of
substrate level phosphorylation.
- The pyruvate
kinase is a key glycolytic enzyme. This step is irreversible.
Net energy (ATP) yield per molecule of Glucose in Glycolysis
Energy Yield in
Aerobic Glycolysis
|
Phase |
Step/Reaction |
Enzyme |
ATP Produced |
ATP Consumed |
|
Investment Phase |
Glucose → Glucose-6-phosphate |
Hexokinase |
0 |
1 |
|
Fructose-6-phosphate → Fructose-1,6-bisphosphate |
Phosphofructokinase-1 (PFK-1) |
0 |
1 |
|
|
Subtotal (Investment) |
0 |
2 ATP |
||
|
Payoff Phase |
1,3-Bisphosphoglycerate → 3-Phosphoglycerate (×2) |
Phosphoglycerate kinase |
2 |
0 |
|
Phosphoenolpyruvate → Pyruvate (×2) |
Pyruvate kinase |
2 |
0 |
|
|
2 NAD⁺ → 2 NADH (via G3P dehydrogenase) |
G3P Dehydrogenase |
6 ATP |
0 |
|
|
Subtotal (Payoff) |
10 ATP |
0 |
||
|
Net ATP Gain |
10 – 2 = 8 ATP |
- Glycolysis
is the only pathway that is taking place in all the cells of the body.
- Glycolysis
is the only source of energy in erythrocytes.
- In strenuous
exercise, when muscle tissue lacks enough oxygen, anaerobic glycolysis
forms the major source of energy for muscles.
- The
glycolytic pathway may be considered as the preliminary step before
complete oxidation.
- The
glycolytic pathway provides carbon skeletons for synthesis of
non-essential amino acids as well as glycerol part of fat.
- Most of the
reactions of the glycolytic pathway are reversible, which are also used
for gluconeogenesis.
The citric acid cycle is also called the Krebs cycle, after Hans Krebs, who first proposed its cyclic nature. The Krebs' cycle reactions take place in the matrix of the mitochondria.
Reaction 1: Formation
of Citric Acid or citrate
The cycle begins when the
two-carbon compound acetyl-CoA combines with the four-carbon compound
oxaloacetate to produce citrate. Due to the formation of citrate, the Krebs
cycle is also known as the citric acid cycle. Citrate is a tricarboxylic acid,
and the Krebs cycle is also known as the tricarboxylic acid (or TCA) cycle. This reaction is catalyzed by citrate
synthase.
Reaction 2:
Isomerization of Citrate
Citrate is rearranged into cis-aconitate,
and then into isocitrate (both are still 6-carbon molecules). This
process involves a sequential dehydration and hydration reaction, to form the
D-Isocitrate isomer with cis-Aconitase as the intermediate. A single enzyme, aconitase,
performs this two-step process.
Reaction 3: Dehydrogenation
I
Isocitrate undergoes dehydrogenation (loses electrons), in
the presence of the enzyme isocitrate dehydrogenase forming an
intermediate called oxalosuccinate. This step produces NADH,
a molecule that carries energy.
Reaction 4: Decarboxylation I
Oxalasuccinate
undergoes decarboxylation to form alpha-ketoglutarate. One CO₂
is removed so alpha-ketoglutarate has 5 carbon. The enzyme involved is
Carboxylase.
Reaction 5: Dehydrogenation II and Decarboxylation
II
Alpha-ketoglutarate
is further oxidized, and another carbon atom is removed as CO₂
, forming succinyl-CoA (a 4-carbon molecule). Two hydrogens and 2 electrons are transferred to NAD+ to NADH + H+. This step also produces NADH,
with the help of the enzyme alpha-ketoglutarate dehydrogenase complex.
Reaction 6: Energy Production/Phosphorylation
of ADP
Succinyl-CoA
is converted into succinate, releasing energy to form GTP
(a molecule similar to ATP).The enzyme for this step is succinic
thiokinase.
Reaction 7: Dehydrogenation
III
Succinate
undergoes dehydrogenation or oxidized into fumarate under the action of the
enzyme succinate dehydrogenase and this reaction
produces FADH₂, another energy-carrying molecule.
Reaction 8: Hydration
Fumarate
is then hydrated (water is added) to form malate, with the
help of fumarase.
Reaction 9: Dehydrogenation
IV
In the final reaction,
malate is transformed into oxaloacetate, which is thus regenerated. The
catalytic enzyme is malate dehydrogenase. The coenzyme NAD+ causes the transfer
of two hydrogens and 2 electrons to NADH + H+.
Significance
of Krebs Cycle
1.
Intermediate compounds
formed during the Krebs cycle are used for the synthesis of biomolecules like
amino acids, nucleotides, chlorophyll, cytochromes, fats etc.
2.
Intermediate like
succinyl CoA takes part in the formation of chlorophyll.
3.
Amino Acids are formed
from α- Ketoglutaric acid, pyruvic acids, and oxaloacetic acid.
4.
Krebs cycle (citric acid
cycle) releases plenty of energy (ATP) required for various metabolic
activities of the cell.
5.
By this cycle, carbon skeletons
are obtained, which are used in the process of growth and for maintaining the
cells.
ATP
calculation for the TCA cycle
One Turn of the TCA
Cycle
|
Step in TCA
Cycle |
Co-enzyme
Produced |
ATP Yield
(classical) |
|
Isocitrate → α-Ketoglutarate |
1 NADH |
3 ATP |
|
α-Ketoglutarate → Succinyl-CoA |
1 NADH |
3 ATP |
|
Succinyl-CoA → Succinate |
1 GTP (→ ATP) |
1 ATP |
|
Succinate → Fumarate |
1 FADH₂ |
2 ATP |
|
Malate → Oxaloacetate |
1 NADH |
3 ATP |
·
Total per turn:
o
NADH = 3 × 3 ATP = 9
ATP
o
FADH₂ = 1 × 2 ATP = 2
ATP
o
GTP = 1 × 1 ATP = 1
ATP
o Sum
= 12 ATP
o
If two molecules of Pyruvate enter TCA cycle
then sum=12x2=24
If we include Step 1: Pyruvate to Acetyl-CoA (Link Reaction), 1 NADH → 3 ATP , 2 pyruvate= 6ATP
For 2 pyruvate:
·
Link reaction = 6 ATP
·
TCA cycle = 24 ATP
·
Glycolysis=8 ATP
·
Total = 38 ATP
Glycogenesis: Synthesis of Glycogen
Glycogenesis is the process of synthesizing glycogen from glucose, occurring in
the cytosol of cells. This process requires ATP, UTP, and glucose
as substrates. Glycogen synthesis is primarily regulated by the availability of
glucose and ATP. When both are abundant, insulin stimulates the conversion of
glucose into glycogen, primarily stored in liver and muscle cells.
In glycogenesis, glucose-6-phosphate, a key
intermediate, plays a central role. It is derived from glucose or as the final
product of gluconeogenesis. For each glucose molecule incorporated into the
glycogen structure, one ATP is consumed. Glycogen’s branched polymeric
structure enables efficient storage and rapid mobilization of glucose when
needed.
STEPS
INVOLVED IN GLYCOGENESIS:
There are 6 major
steps are involved in the Glycogenolysis:
Step
1: Glucose Phosphorylation:
Step
2: Glc-6-P to Glc-1-P conversion:
Step
3: Attachment of UTP to Glc-1-P:
Step
4: Attachment of UDP-Glc to Glycogen Primer:
Step
5: Glycogen synthesis by Glycogen synthase:
Step
6: Glycogen Branches formation:
STEP
1: GLUCOSE PHOSPHORYLATION:
Glucose is phosphorylated into Glucose-6-Phosphate, a reaction that
is common to the first reaction in the pathway of glycolysis from Glucose. This
reaction is catalyzed by Hexokinase in Muscle and Glucokinase in
Liver.
Glucose + ATP –> Glucose-6-P
(Enzyme: Glucokinase or Hexokinase)
STEP 2: GLCose 6-P TO GLuCose-1-P CONVERSION:
Glucose-6-Phosphate is converted to
Glcucose-1-Phosphate in a reaction catalyzed by the enzyme “Phosphoglucomutase”.
Glucose-6-P <—>
Glucose-1-Phosphate
(Enzyme: Phosphoglucomutase)
STEP 3: ATTACHMENT OF UTP TO GLC-1-P:
Glucose-1-P reacts with Uridine triphosphate (UTP) to
form the active nucleotide Uridine diphosphate Glucose (UDP-Glc). The reaction
is catalyzed by the enzyme “UDPGlc Pyrophosphorylase”.
UTP + Glucose-1-P
<—> UDPGlc + PPi
(Enzyme: UDPGlc
Pyrophosphorylase)
STEP 4: ATTACHMENT OF UDP-GLC TO GLYCOGEN PRIMER:
A small fragment of pre-existing glycogen must act as
a “Primer” (also called GLYCOGENIN) to initiate
glycogen synthesis. The Glycogenin can accept glucose from UDP-Glc.
The hydroxyl
group of the amino acid tyrosine of Glycogenin is the site at which the initial
glucose unit is attached. the enzyme Glycogen initiator synthase transfers the
first molecule of Glucose to Glycogenin.
Then
glycogenin itself takes up a for glucose residues to form a fragment of primer
which serves as an acceptor for the rest of the glucose molecules.
STEP 5: GLYCOGEN SYNTHESIS BY GLYCOGEN SYNTHASE:
Glycogen synthase,
the enzyme transfers the Glucose from UDP-Glc to the non-reducing end of
Glycogen to form alpha 1,4-linkages. Glycogen synthase catalyze the synthesis
of a linear unbranched molecule with alpha-1,4-glycosidic linkages.
STEP 6: GLYCOGEN BRANCHES FORMATION:
In this step, the formation of branches is brought
about by the action of a branching enzyme, namely branching
enzyme (amylo-[1—>4]—>[1—>6]-transglucosidase). This
enzyme transfers a small fragment of five to eight glucose residues from the
non-reducing end of glycogen chain. to another glucose residue where it is
linked by alpha-1,6 bond.
It leads to
the formation of a new non-reducing end, besides the existing one. Glycogen
chain wil be elongated and branched.
Overall
reaction of Glycogenesis,
(Glucose)n +
Glucose + 2 ATP –> (Glucose) n+1 + 2 ADP
+ Pi
Two ATP molecules will
utilize in this process. One is required for thephosphorylation
of Glucose and
other is needed for conversion of UDP
to UTP.
Glycogenolysis
Glycogenolysis is the breakdown of glycogen stored in the liver and muscles
into glucose-1-phosphate and eventually into glucose-6-phosphate. This process
is primarily controlled by two hormones:
- Glucagon – Released from the pancreas in
response to low blood glucose levels.
- Epinephrine – Released from the adrenal
glands during stress or threat.
Both hormones activate glycogen phosphorylase to
begin glycogenolysis, while inhibiting glycogen synthase
to stop glycogenesis.
Steps in
Glycogenolysis
Step 1: Glycogen Breakdown: Glycogen, a highly branched polymer of glucose, these glucose molecules are hydrolyzed from its chains.
- Enzyme: Glycogen Phosphorylase
- Reaction: Glycogen → Glucose-1-Phosphate
Description: Glycogen phosphorylase catalyzes the breakdown of glycogen into glucose-1-phosphate by cleaving the α-1,4-glycosidic bonds between glucose units.
· Glycogen phosphorylase breaks the
α-1,4-glycosidic bonds to release glucose-1-phosphate.
· The debranching enzyme has two functions:
- Transferase: moves a block of
three glucose units from a branch to the main chain.
- Glucosidase: hydrolyzes the
α-1,6 bond at the branch point to release free glucose.
Step 2: Conversion of Glucose-1-Phosphate to
Glucose-6-Phosphate: Each glucose molecule is then
phosphorylated at the C-1 position to form glucose-1-phosphate.
- Enzyme: Phosphoglucomutase
- Reaction: Glucose-1-Phosphate ↔ Glucose-6-Phosphate
Description: The enzyme phosphoglucomutase transfers the phosphate group from C-1 to C-6, forming glucose-6-phosphate. This reaction is reversible.
Step 3: Glucose-6-Phosphate Fate: The phosphate
is then shifted from C-1 to C-6, creating glucose-6-phosphate,
a crucial intermediate that can either enter glycolysis for energy production
or be converted back to glucose.
1. If
energy is needed immediately (via glycolysis):
- Enzyme: Phosphoglucose Isomerase
- Reaction: Glucose-6-Phosphate → Fructose-6-Phosphate (via glycolysis)
Description: Glucose-6-phosphate enters glycolysis to be converted into pyruvate and provide energy.
2. If
energy is not immediately needed (conversion to glucose):
- Enzyme: Glucose-6-Phosphatase (in liver cells)
- Reaction: Glucose-6-Phosphate → Glucose
Description: In the liver, glucose-6-phosphate is converted back into glucose by glucose-6-phosphatase. The glucose is then released into the bloodstream for distribution to cells, such as brain cells, for energy.
Fate of Glucose-6-Phosphate
- Energy Production: If the body needs energy
immediately, glucose-6-phosphate enters the glycolysis pathway.
- Storage or Distribution: If energy is not
needed immediately, glucose-6-phosphate is converted back into glucose,
which is released into the blood for use by other cells, such as brain
cells.
Hormonal Regulation of
Glycogenolysis
- Glucagon (in liver)
and Epinephrine (in muscles) stimulate glycogen phosphorylase
activity to initiate glycogen breakdown.
- Insulin inhibits
glycogenolysis and promotes glycogenesis.
Blood Sugar
Level
·
Blood sugar level (also called blood glucose
level) is the amount of glucose present in the blood at a given time.
·
Normal Range:
o
Fasting (no food for 8 hours): 70–100
mg/dL
o
After eating (postprandial): Less
than 140 mg/dL
These values can vary slightly depending on the lab and individual.
Significance
of Blood Sugar Level
1. Energy
Source:
Glucose is the main energy source for the body's cells, especially the brain.
2. Indicator
of Metabolic Health:
Maintaining normal blood sugar is vital for overall health and metabolism.
3. Diabetes
Diagnosis:
o
High blood sugar (hyperglycemia) can indicate diabetes
mellitus or pre-diabetes.
o
Low blood sugar (hypoglycemia) can cause
weakness, confusion, and if severe, loss of consciousness.
4. Monitoring
Treatment:
Blood sugar levels are routinely monitored in diabetic patients to adjust
medication, diet, and lifestyle.
5. Preventing
Complications:
Chronic high blood sugar can lead to complications like heart disease, kidney
failure, nerve damage, and vision problems.
Hyperglycemia
(High Blood Sugar)- Blood glucose
level is higher than normal, usually above 126 mg/dL (fasting) or above 200
mg/dL (random).
·
Causes:
o
Diabetes mellitus
(most common cause)
o
Stress or illness (can increase blood sugar)
o
Excessive intake of sugary foods or
carbohydrates
o
Insufficient insulin or antidiabetic medication
o
Hormonal disorders like Cushing’s syndrome or
hyperthyroidism
o
Certain medications (e.g., corticosteroids)
·
Symptoms:
Increased thirst, frequent urination, fatigue, blurred vision, weight loss.
Clinical Implications of Hyperglycemia (High Blood Sugar)
Short-term effects:
·
Polyuria:
Excess glucose causes increased urination.
·
Polydipsia:
Excessive thirst due to dehydration.
·
Fatigue and weakness:
Cells can’t effectively use glucose without insulin.
·
Blurred vision:
High glucose causes fluid shifts in the eye.
·
Infections:
High blood sugar impairs immune function, increasing infection risk.
·
Diabetic ketoacidosis
(DKA): Mainly in type 1 diabetes; severe insulin deficiency
leads to ketone production, causing acidosis, dehydration, and can be
life-threatening.
·
Hyperosmolar
hyperglycemic state (HHS): Mostly in type 2 diabetes; very high
blood sugar without ketones but severe dehydration and altered consciousness.
Long-term complications:
·
Microvascular damage:
o
Diabetic retinopathy → vision loss
o
Diabetic nephropathy → kidney failure
o
Diabetic neuropathy → nerve damage causing pain,
numbness
·
Macrovascular damage:
o
Increased risk of heart disease, stroke, and peripheral arterial disease.
·
Poor wound healing:
Leading to ulcers, especially foot ulcers.
Hypoglycemia
(Low Blood Sugar)- Blood glucose
level falls below normal, typically under 70 mg/dL.
·
Causes:
o
Excess insulin or antidiabetic drugs in diabetic
patients
o
Skipping meals or fasting
o
Excessive physical activity without proper food
intake
o
Alcohol consumption without eating
o
Certain illnesses like insulinoma (tumor
producing insulin)
o
Hormonal deficiencies (e.g., adrenal
insufficiency)
·
Symptoms:
Sweating, shakiness, confusion, dizziness, irritability, in severe cases
seizures or loss of consciousness.
Clinical Implications of Hypoglycemia (Low
Blood Sugar)
Mild to moderate symptoms:
·
Shakiness, sweating, palpitations
·
Hunger
·
Anxiety, irritability
·
Dizziness or headache
·
Difficulty concentrating or confusion
Severe symptoms:
·
Seizures or convulsions
·
Loss of consciousness (coma)
·
If untreated, it can cause brain damage or death
Diabetes Mellitus and Its Types
Diabetes mellitus is a chronic metabolic disorder characterized by high
blood sugar (hyperglycemia) due to problems with insulin secretion
or action.
·
Cause: Autoimmune destruction of pancreatic beta
cells → little or no insulin production
·
Usually diagnosed in children and young adults
·
Requires lifelong insulin therapy
·
Symptoms: sudden onset of polyuria, polydipsia,
weight loss, fatigue
·
Cause: Insulin resistance combined with relative
insulin deficiency
·
More common in adults but increasingly seen in
younger people due to obesity
·
Managed with lifestyle changes, oral
hypoglycemic drugs, and sometimes insulin
·
Symptoms: gradual onset, sometimes asymptomatic
initially
·
Occurs during pregnancy
·
Due to hormonal changes causing insulin
resistance
·
Usually resolves after delivery but increases
risk of type 2 diabetes later
- Random Plasma Glucose: Identifies severe
hyperglycemia.
- Fasting Plasma Glucose (FPG): Diagnoses
diabetes and prediabetes.
- Oral Glucose Tolerance Test (OGTT):
Evaluates how the body handles glucose over time.
- HbA1c: Indicates average blood glucose
levels over 2–3 months.
1. Random Plasma Glucose (RPG)
Principle: Measures blood glucose at any random
time regardless of the last meal. Useful to detect marked hyperglycemia.
Procedure:
·
A blood sample is taken randomly without
fasting.
·
Plasma glucose is measured by enzymatic methods
(e.g., glucose oxidase).
Interpretation:
·
≥ 200 mg/dL
with classic symptoms of diabetes (polyuria, polydipsia, weight loss) indicates
diabetes.
·
Values below 200 mg/dL may need further testing.
2. Fasting Plasma Glucose (FPG)
Principle: Measures blood glucose after at least
8 hours of fasting to assess baseline glucose regulation.
Procedure:
·
Patient fasts overnight (8-12 hours).
·
Blood sample collected in the morning.
·
Plasma glucose measured enzymatically.
Interpretation:
·
Normal:
<100 mg/dL
·
Impaired Fasting
Glucose (Prediabetes): 100–125 mg/dL
·
Diabetes:
≥126 mg/dL on two separate occasions
3. Oral Glucose Tolerance Test (OGTT)
Principle:
Evaluates the body’s ability to clear glucose from the blood after a
standardized glucose load.
Procedure:
·
Patient fasts overnight.
·
A fasting blood sample was taken.
·
Patient drinks 75 grams of glucose dissolved in
water.
·
Blood samples were taken at 30 minutes, 1 hour,
and especially 2 hours after ingestion.
·
Plasma glucose is measured each time.
Interpretation (2-hour value):
·
Normal:
<140 mg/dL
·
Impaired Glucose
Tolerance (Prediabetes): 140–199 mg/dL
·
Diabetes:
≥200 mg/dL
Note- During an OGTT, blood
glucose is measured at fasting (0 min) and at
intervals after glucose ingestion (typically 30 min, 1 hour, and 2
hours). The 2-hour plasma glucose is
the standard diagnostic value recommended by the WHO
and ADA for identifying diabetes or impaired glucose tolerance. Earlier time
points (30 min, 1 hour) can show how quickly glucose rises and falls, but they
are not standardized for diagnosis.The 2-hour
glucose level reflects how well the body clears glucose over a
reasonable period and is best correlated with risk of diabetes complications.
4. HbA1c (Glycated Hemoglobin)
Principle:Measures the percentage of hemoglobin
that is glycated (bound to glucose). Reflects average blood glucose over the
past 2–3 months (lifespan of red blood cells).
·
HbA1c (Glycated
Hemoglobin) is a form of hemoglobin that has glucose molecules
attached to it. It reflects the average blood sugar
levels over the past 2 to 3 months.
·
Used mainly to monitor long-term glucose control
in people with diabetes.
HbA1c
Formation
·
When glucose circulates in the blood, some of it
non-enzymatically binds to hemoglobin molecules
inside red blood cells.
·
This process is called glycation.
The binding happens slowly and permanently during the lifespan of red blood
cells (about 120 days). The amount of HbA1c formed is proportional to the
average blood glucose concentration over time.
So, higher blood sugar → more glucose binds to hemoglobin → higher HbA1c.
Procedure:
·
Blood sample taken any time (fasting not
required).
·
Measured by methods such as high-performance liquid
chromatography (HPLC).
Interpretation:
·
Normal:
Below 5.7%
·
Prediabetes:
5.7% to 6.4%
·
Diabetes:
6.5% or higher on two occasions
Example Test Results
|
Test |
Result |
Interpretation |
|
HbA1c |
7.2% |
Indicates diabetes
(≥6.5%) |
|
OGTT (2-hour glucose) |
210 mg/dL |
Indicates diabetes
(≥200 mg/dL) |
·
The HbA1c of 7.2%
shows the person has an average blood sugar above normal for the last 2–3
months, consistent with diabetes.
·
The OGTT 2-hour glucose value of 210
mg/dL confirms impaired glucose handling and supports the
diagnosis of diabetes.
Comments
Post a Comment