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Course Code: 08111101 Course Title: General Biochemistry

Title/Topic: NAVIGATING BIOCHEMICAL PATHWAYS OF CARBOHYDRATE METABOLISM

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2 Organization (1)
3 Content (2)
4 Time Management (1)
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2 Knowledge and Interaction (2)
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Date of Submission: 27.04.2024 ……………………………

Teacher Signature

Semester: Spring Year: 2024 Level-Term: 1.1 Section: A

Submitted by- Submitted to-

Name:- Kanta Mondol Submitted to: - Md.Shoaib Arifin
Id:-0242410001101028 Lecturer
Department: Agricultural Science
Daffodil International University
Topics:

 1."Exploring Glycolysis: Unraveling the First Step in

Carbohydrate Metabolism" by Kanta Mondol

 2."The Tricarboxylic Acid (TCA) Cycle: A Deep Dive into Cellular

Energy Production" by Zannatul Mawa

 3."Gluconeogenesis: The Reverse Pathway of Carbohydrate

Metabolism" by Sabbir Ahmed

 4."Glycogenesis and Glycogenolysis: Balancing Glucose Storage

and Release" by Md Ashraful Islam

 5." Regulation of Carbohydrate Metabolism at the Cellular and

Enzymatic Level" by Nayem Mollah
 Exploring Glycolysis: Unraveling the First Step in Carbohydrate
Metabolism

Definition of Carbohydrate:
Carbohydrates are polyhydroxy aldehydes or ketones or substances
that produce such compounds on hydrolysis.
Definition of Carbohydrate Metabolism:
Carbohydrate metabolism is the process by which carbohydrates are
broken down, converted, and utilized by living organisms to produce
energy and synthesize biomolecules essential for cellular function.

Pathways of Carbohydrate metabolism:

Carbohydrate metabolism involves several interconnected pathways
within cells:
1. Glycolysis: The breakdown of glucose into pyruvate, generating ATP
and NADH.
2. Gluconeogenesis: The synthesis of glucose from non-carbohydrate
precursors like lactate, glycerol, or amino acids.
3. Glycogenesis: The formation of glycogen from glucose for energy
storage.
4. Glycogenolysis: The breakdown of glycogen into glucose for energy
release.
5. Pentose Phosphate Pathway (PPP): Generates NADPH and ribose-5-
phosphate for nucleotide synthesis.
6. Citric Acid Cycle (Krebs Cycle): Oxidizes acetyl-CoA to generate
NADH, FADH2, and ATP.
 GLYCOLYSIS

Definition: Glycolysis is the metabolic pathway that converts

glucose into pyruvate, producing ATP and NADH in the process.
Occurrence: Glycolysis occurs in the cytoplasm of the cells. It
occurs in the absence of oxygen that’s called anaerobic or in
the presence of Oxygen called aerobic.
Glycolysis has a dual role.
I. It generates ATP for providing energy.
II. Produces intermediates that act as precursors for
biosynthetic process.
The Tricarboxylic Acid (TCA) Cycle: A Deep Dive into Cellular Energy
Production
Definition: -
 The tricarboxylic acid cycle (TCA cycle) is a series of enzyme
catalyzed chemical reactions that form a key part of aerobic
respiration in cells.
 This cycle is also called the Kreb's cycle and citric acid cycle.
Step Of The TCA Cycle:-
The TCA cycle is a central pathway that provides a unifying point for
many metabolites, which feed into it at various points. It takes place
over eight different steps:
Step 1: Acetyl CoA (two-carbon molecule) joins with oxaloacetate
(four-carbon molecule) to form citrate (six-carbon molecule).
Step 2: Citrate is converted to isocitrate (an isomer of citrate)
Step 3: Isocitrate is oxidized to alpha-ketoglutarate (a five-carbon
molecule) which results in the release of carbon dioxide. One NADH
molecule is formed.
Step 4: Succinyl CoA is then converted to succinate (four-carbon
molecule) and one GTP molecule is produced.
Step 5: Succinate is converted into fumarate (four-carbon molecule)
and a molecule of FADH₂ is produced.
Step 6: Fumarate is converted to malate (another four-carbon
molecule).
Step 7: Malate is then converted into oxaloacetate. The third
molecule of NADH is also produced.
Regulation of the TCA Cycle: -
This process is regulated in a variety of ways: -
#Metabolites: Products of cycle provide negative feedback on the
enzymes that catalyze it. For example, NADH inhibits most of the
enzymes found in the cycle.
#Citrate: Inhibits phosphofructokinase, a key enzyme in glycolysis.
This reduces the rate of production of pyruvate and therefore of
acetyl-CoA.
#Calcium: Accelerates the TCA cycle by stimulating the link reaction.

Signification Of TCA Cycle: -

1.Intermediate like succinyl CoA takes part in the formation of
Chlorophyll
2. Amino acids are formed from Alfa - ketoglutaric acid, pyruvic acid
and oxaloacetic acid.
3. Kreb's cycle releases plenty of energy required for various
metabolic activities of a cell.

TCA Cycle:-
ATP Generation
Total ATP = 12 ATP
3 NAD+ = 9 ATP
1 FAD = 2 ATP
1 GDP = 1 ATP
 Gluconeogenesis: The Reverse Pathway of Carbohydrate
Metabolism
GLUCONEOGENESIS
• Formation of glucose or glycogen from non-carbohydrate
precursor is called gluconeogenesis
Importance of Gluconeogenesis:
• Maintain blood glucose concentration during fasting, starvation &
limited carbohydrate intake. This is necessary especially for the
nervous system & erythrocytes.

Salient features
• Substrate:
✓Glucogenic amino acid
✓ Lactate
✓ Glycerol
✓Fatty acid
✓Pyruvate
✓Intermediates of TCA cycle
✓Propionates
• Product: Glucose
• Site:
• Liver (90%)
• Kidney (10-40%)
• Intestine
• Compartment: Cytoplasm & mitochondria
• Nature: Anabolic
Importance of gluconeogenesis
• Failure of gluconeogenesis is usually fatal. Hypoglycemia causes
brain dysfunction, which can lead to coma & death • Maintain
adequate concentration of intermediates of citric acid cycle.
• Clear the product of metabolism of other tissue from blood.
Example-Lactate produced in muscle & RBC; glycerol continuously
produced in adipose tissue.
• Excessive gluconeogenesis occurs in critically ill patients in
response to injury & infection, contributing to hyperglycemia.

Steps of Gluconeogenesis
⚫ It involves glycolysis, the citric acid cycle and some other
reactions
• Glycolysis and gluconeogenesis share the same pathway but in
opposite directions
• Three nonequilibrium reactions in glycolysis prevent simple
reversal of glycolysis. The reactions are catalyzed by-
• Hexokinase
• Phosphofructokinase
• Pyruvate kinase
Steps of Gluconeogenesis
 Reaction catalyzed by phosphofructokinase: The conversion of
fructose 1,6-bisphosphate to fructose-6- phosphate is catalyzed
by fructose 1,6-bisphosphatase.
 Reaction catalyzed by hexokinase: The conversion of glucose-6-
phosphate to glucose is catalyzed by glucose-6-phosphatase. It
is present in liver & kidney but absent from muscle, which
cannot export glucose into bloodstream.

Regulation of gluconeogenesis
• Glucagon & epinephrine
• Substrate availability
• Enzyme
• Pyruvate carboxylase • PEP carboxykinase
• Fructose 1,6 bis-phosphatase Glucose 6 phosphatase
 Glycogenesis and Glycogenolysis: Balancing Glucose Storage and
Release

Glycogenesis is the process of converting glucose into glycogen.

Glycogen is a multi-branched polysaccharide that serves as a form of
energy storage in animals and fungi, primarily found in the liver and
muscle cells. When blood glucose levels are high, such as after a
meal, the body converts excess glucose into glycogen for storage.
This process is catalyzed by the enzyme glycogen synthase with the
aid of other enzymes like branching enzymes.

Glycogenolysis is the reverse process, where glycogen is broken

down into glucose molecules when the body needs energy. This
happens during fasting or intense physical activity. The enzyme
glycogen phosphorylase plays a major role in breaking down
glycogen into glucose-1-phosphate, which is then converted into
glucose-6-phosphate. This can enter the glycolysis pathway to
produce energy or can be converted to glucose and released into
the bloodstream, particularly from the liver.
Difference between Glycogenolysis and Glycogenesis
Serial Glycogenolysis Glycogenesis
No.
1. Breakdown of glycogen to Synthesis of glycogen from glucose
glucose
2. Stimulated by fasting, between Stimulated by increased blood
meals physical exercise, glucose level as in well fed state,
glucagon, epinephrine insulin
3. Inhibited by insulin Inhibited by glucagon, epinephrine
4. Glycogen phosphorylase is the Glycogen synthase is the key
key enzyme which is enzyme which is dephosphorylated
phosphorylated in its active in active form
form

Both processes are tightly regulated by hormonal signals. Insulin

promotes glycogenesis, signaling cells to store glucose when it is
abundant. In contrast, glucagon and adrenaline stimulate
glycogenolysis, signaling the release of glucose into the blood when
it is needed, ensuring that energy levels remain constant through
various conditions.
 Regulation of Carbohydrate Metabolism at the Cellular and
Enzymatic Level
The changes in the metabolism fully de-pend on the changes in the
availability of substrates. The concentration of glucose, fatty acids
and amino acids in blood in-fluences their rate and pattern of
metabo-lism in many tissues.
Alterations in the concentrations of glu-cose, fatty acids and amino
acids in the blood owing to the changes in the dietary availability
may alter the rate of secretion of hormones that influence the
pattern of metabolism in metabolic pathways.

Three types of mechanisms are responsi-ble for regulating the

activity of enzymes concerned in carbohydrate metabolism:
(i) Changes in the rate of enzyme syn-thesis.
(ii) Conversion of an inactive to an ac-tive enzyme.
(iii) Allosteric effects.
Regulation of Glycolysis, Gluconeo-Genesis and Hexose
Monophosphate Shunt:
a. Glucokinase catalyzes the conversion of glucose to glucose-6-
phosphate. In the same extra mitochondrial region glucose- 6-
phosphatase is also found which catalysis the same inter-conversion
in the reverse direction on the supply of sufficient car-bohydrate,
glucokinase activity is in-creased whereas glucose-6-phosphatase
activity is decreased. In starvation, glu-cokinase activity falls as
compared to glucose-6-phosphatase activity.
b. Under the availability of glucose the en-zymes utilizing glucose
are all activated but the enzymes producing glucose by
gluconeogenesis are all depressed. The secretion of insulin controls
the activity of the enzymes responsible for glycolysis as well as
gluconeogenesis.
c. Both dehydrogenases of the HMP shunt are adaptive enzymes
since their activity is increased in the well-fed animal as well as
when insulin is given to a diabetic animal. Their activity is low in
diabetes or fasting. Similar behavior has been found in “Malic
enzyme” and ATP-dtrate lyase. This indicates that these two
enzymes are involved in lipogenesis rather than glu-coneogenesis.
d. The activity of pyruvate dehydrogenase is decreased since it is
regulated by phos-phorylation involving an ATP-specific kinase and
its activity is increased by de-phosphorylation by a phosphatase.
Thus, pyruvate dehydrogenase is inhibited dur-ing fatty acid
oxidation. Its activity is in-creased after administration of insulin and
decreased in starvation.
e. The allosteric control of the activity of an enzyme is also available
in carbohydrate metabolism. In gluconeogenesis, the syn-thesis of
oxaloacetate from pyruvate by the enzyme pyruvate carboxylase
requires the presence of acetyl-CoA as an allos-teric activator.
Regulation of Glycogen Metabolism:
a. Glycogen metabolism regulation is af-fected by the balance in
activation be-tween the enzymes of glycogen synthesis and those of
glycogen breakdown as well as the hormonal control.
b. Cyclic AMP-dependent protein kinase ac-tivates phosphorylase b
kinase and inac-tivates glycogen synthetase. Thus, inhi-bition of
glycogenolysis promotes glyco-genosis and inhibition of glycogenesis
enhances glycogenolysis.
c. Glycogen metabolism in the liver is con-trolled by the
concentration of phospho-rylase a. This enzyme not only controls
the rate-limiting step in glycogenolysis but also inhibits the activity
of synthetase, phosphatase and thereby controls glyco-gen
synthesis.
d. Inactivation of phosphorylase is caused by glucose and activation
is caused by 5′- AMP.
Regulation of the Citric Acid Cycle:
a. The activity of the enzymes of Citric acid cycle is immediately
dependent on the supply of oxidized dehydrogenase cofactors
which, in turn, is de-pendent on the availability of ADP and
ultimately on the rate of utilization of ATP.
b. Control of the citric acid cycle occurs at the pyruvate
dehydrogenase step. Control may be experienced by allosteric
inhibi-tion of citrate synthase by ATP or long chain fatty acyl-CoA.
c. Oxaloacetate inhibits succinate dehydro-genase and the
availability of oxaloace-tate, as controlled by malate
dehydroge-nase, depends on the ratios of the concen-trations of
NADH and NAD+.
d. The increase in the ratio of the concentra-tion of ATP and ADP is
considered to raise the ratio of the concentration of GTP and GDP at
the succinate thiokinase step, thereby increasing the concentration
of succinyl-CoA.
Conclusion:

Navigating the biochemical pathways of carbohydrate metabolism is

akin to traversing a complex network of interconnected roads, each
leading to different destinations crucial for cellular function and
energy production. From glycolysis to gluconeogenesis, from
glycogenesis to glycogenolysis, and from the TCA cycle to oxidative
phosphorylation, these pathways intricately regulate the flow of
carbon and energy molecules, adapting to varying metabolic
demands and environmental conditions, Understanding the routes,
regulatory checkpoints, and crosstalk between pathways is essential
for deciphering how cells manage energy balance, respond to
dietary changes, and adapt to physiological challenges