1. Glycolysis is the breakdown of glucose to pyruvate with production of ATP. Glycolysis occurs in the cytoplasm and is the first step of carbohydrate metabolism. 2. The citric acid cycle (Krebs cycle) occurs in the mitochondria and involves the oxidation of acetyl CoA derived from pyruvate to carbon dioxide. This produces NADH and FADH2 to be used in the electron transport chain for ATP production. 3. Glycogenesis is the formation of glycogen from glucose-6-phosphate in the liver and muscle cells for energy storage. Glycogenolysis breaks down glycogen back to glucose-6-phosphate to regulate blood glucose levels.

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Prepared by:
Ms. Shivanee Vyas
Assistant Professor
SVKM’s, NMIMS, School of Pharmacy and Technology Management

2. A living cell coordinates hundreds of reactions. Metabolism includes the all
chemical reactions of a living system.
Metabolism is broadly divided into two categories:
1. Anabolism: The biosynthetic reactions involving the formation of complex molecules from simple
precursors.
2. Catabolism: The degradative processes concerned with the breakdown of complex molecules into simpler
ones, and release the of energy.
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3.  All living cells require energy to carry out various cellular activities.
 This energy is stored in organic molecules (e.g. carbohydrates, fats, proteins) that we eat as
food.
 These organic molecules are broken down into smaller units: proteins into amino acids,
polysaccharides into simple sugars, and fats into fatty acids and glycerol by enzymatic
reactions in cells to generate energy in the form of Adenosine Triphosphate (ATP).
 The ATP generated by these pathways in cells is used to drive fundamental cellular processes.
 Glucose is utilized as a source of energy, & stored as glycogen to release glucose as & when
the need arises.
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4. 1. Glycolysis: The oxidation of glucose to pyruvate and lactate.
2. Citric Acid Cycle: (Krebs Cycle): The oxidation of acetyl CoA to CO2.
3. Gluconeogenesis: The synthesis of glucose from non-carbohydrate precursors (e.g. amino acids, glycerol etc.).
4. Glycogenesis: The formation of glycogen from glucose.
5. Glycogenolysis: The breakdown of glycogen into glucose.
6. Hexose Monophosphate Shunt: It is the alternative pathway to glycolysis & TCA cycle for the oxidation of glucose.
7. Uronic acid pathway: Glucose is converted to glucuronic acid, pentoses and, in some animals, to ascorbic acid (not in
man)
8. Galactose metabolism: The pathways concerned with the conversion of galactose to glucose and the synthesis of
lactose.
9. Fructose metabolism: The oxidation of fructose to pyruvate and the relation between fructose and glucose metabolism.
10. Amino sugar and mucopolysaccharide metabolism: The synthesis of amino sugars and other sugars for the formation
of mucopolysaccharides and glycoproteins.
MAJOR PATHWAYS OF CARBOHYDRATE METABOLISM:
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5. Glycolysis is derived from the Greek words (glycose—sweet or sugar; lysis—dissolution). Glycolysis is
defined as the sequence of reactions converting glucose (or glycogen) to pyruvate or lactate, with the
production of ATP. It is a universal pathway in living cells.
Site of reaction: All the reaction steps take place in the cytoplasm.
Importance of the glycolysis pathway:
1. It is the only pathway that is taking place in all the cells of the body.
2. Glycolysis is the only source of energy in erythrocytes.
3. In exercise, when muscle tissue lacks enough oxygen, anaerobic glycolysis forms the major source of energy
for muscles.
4. The glycolytic pathway provides carbon skeletons for the synthesis of nonessential amino acids as well as the
glycerol part of fat.
5. Most of the reactions are reversible.
GLYCOLYSIS (EMBDEN-MEYERHOF PATHWAY)
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7. 1. Glucose is phosphorylated to glucose-6-phosphate. The
enzyme is hexokinase, which splits ATP into ADP and the Pi is
added to the glucose and the reaction is irreversible.
2. Glucose-6-phosphate is isomerised to fructose-6-phosphate by
phosphohexose isomerase.
3. Fructose-6-phosphate is further phosphorylated to fructose-
1,6-bisphosphate. The enzyme is phosphofructokinase, it is an
important key enzyme and the reaction is irreversible.
4. The fructose-1,6-bisphosphate is split into two three-carbon
compounds, glyceraldehyde 3-phosphate and
dihydroxyacetone phosphate by the enzyme aldolase.
5. Dihydroxyacetone phosphate is isomerized to glyceraldehyde-
3-phosphate by the enzyme phophotriose isomerase.
6. Glyceraldehyde-3-phosphate is dehydrogenated and
simultaneously phosphorylated to 1,3-bisphosphoglycerate
with the help of NAD+ + 2Pi. The enzyme is glyceraldehyde-
3-phosphate dehydrogenase.
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8. 7. 1,3-bis-phosphoglycerate is converted to 3-
phosphoglycerate by the enzyme 1, 3-
bisphosphoglycerate kinase. Here, one molecule of ATP is
formed; this reaction is an example of Substrate level
phosphorylation.
8. 3-phosphoglycerate is isomerised to 2-phosphoglycerate
by the enzyme phosphoglycerate mutase.
9. 2-phosphoglycerate is converted to phosphoenolpyruvate
by the enzyme enolase. One water molecule is removed.
A high-energy phosphate bond is produced. This enzyme
requires Mg++ and is inhibited by fluoride.
10. Phosphoenolpyruvate is dephosphorylated to pyruvate, by
pyruvate kinase. One molecule of ATP is generated. This
step is irreversible.
Phosphohexose isomerase
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9. Production of ATP in glycolysis
Under anaerobic conditions, 2 ATP are synthesized while, under aerobic conditions, 8 ATP are synthesized.
Net Reaction
GLUCOSE + 2ADP + 2Pi + 2NAD+ 2PYRUVATE + 2ATP + 2NADH
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10. The cycle was proposed by Hans Adolf Krebs in 1937.
• The citric acid cycle (Krebs cycle or tricarboxylic acid—
TCA cycle) is the most important metabolic pathway for
the energy supply to the body.
• About 65-70% of the ATP is synthesized in the Krebs
cycle.
• The enzymes of the TCA cycle are located in the
mitochondrial matrix.
• It involves the oxidation of acetyl CoA to CO2 and H2O.
CITRIC ACID CYCLE (KREBS CYCLE)
An overview of the Krebs cycle
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12. 1. Step 1
 The acetic acid subunit of acetyl CoA is combined with oxaloacetate to form a molecule of citrate.
 The acetyl coenzyme A acts only as a transporter of acetic acid from one enzyme to another.
 After Step 1, the coenzyme is released by hydrolysis so that it may combine with another acetic acid molecule
to begin the Krebs cycle again.
2. Step 2
 The citrate molecule undergoes isomerization to isocitrate by the enzyme aconitase. A hydroxyl group and a
hydrogen molecule are removed in the form of water.
 This is achieved in a two-stage reaction of dehydration followed by hydration through the formation of an
intermediate—cis-aconitate.
3. Step 3
 In this step, the isocitrate molecule is oxidized by a NAD molecule in the presence of Isocitrate dehydrogenase.
NAD binds with a hydrogen atom and carries off the other hydrogen atom leaving a carbonyl group. This
structure is very unstable, so a molecule of CO2 is released creating alpha-ketoglutarate.
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13. 6. Step 6
 Succinyl CoA is converted to succinate by succinate thiokinase. This reaction is coupled with the
phosphorylation of GDP to GTP. This is substrate-level phosphorylation. GTP is converted to ATP by the
enzyme nucleoside diphosphate kinase.
GTP + ADP ↔ ATP + GDP
4. Step 4
 The enzyme isocitrate dehydrogenase (ICD) catalyses the conversion (oxidative decarboxylation) of isocitrate
to oxalosuccinate and then to D-ketoglutarate. The formation of NADH and the liberation of CO2 occur at this
stage.
5. Step 5
 A water molecule sheds its hydrogen atoms to coenzyme A. Then, a free-floating phosphate group displaces
coenzyme A and forms a bond with the succinyl complex.
 The phosphate is then transferred to a molecule of GDP to produce an energy molecule of GTP. It leaves
behind a molecule of succinate.
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14. 7. Step 7
 An enzyme fumarase adds water to the fumarate molecule to form malate.
8. Step 8
 In this final step, the malate molecule is oxidized by a NAD molecule. The carbon that carried the hydroxyl
group is now converted into a carbonyl group.
 The end product is oxaloacetate which can then combine with acetyl-coenzyme A and begin the Krebs cycle
all over again
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15. Summary of TCA cycle
The events of the Krebs cycle may be summarized as:
Acetyl CoA + 3 NAD+ + FAD + GDP + Pi +2H2O 2CO2 + 3NADH + 3H+ + FADH2 + GTP +
CoA
• In summary, three major events occur during the Krebs cycle.
 One GTP (guanosine triphosphate) is produced which eventually donates a phosphate group to ADP to form
one ATP; three molecules of NAD are reduced, and one molecule of FAD (flavin adenine dinucleotide) is
reduced.
 Although one molecule of GTP leads to the production of one ATP, the production of the reduced NAD and
FAD are far more significant in the cell’s energy-generating process.
 This is because NADH (Nicotinamide adenine dinucleotide) and FADH2 donate their electrons to an electron
transport system that generates large amounts of energy by forming many molecules of ATP.
Yield of ATP
 At this point, the yield of ATP is 4 moles per mole of Glucose as it passes through the Krebs cycle.
 This is not much more than the 2 moles which would have been produced from glycolysis.
 However, NADH and FADH2 are energy-rich molecules
 Oxidation of 1 mole NADH produces 3 moles of ATP
 Oxidation of 1 mole FADH2 produces 2 moles of ATP
 Thus total ATP yield = 8 (Glycolysis) + 6 NAD + 4 FAD + 2 ATP + (6 NAD at Pyruvic acid to Acetyl Co-A) =
38 moles ATP per mole Glucose 15

16. • Glycogenesis is the formation of glycogen
from glucose. Glycogen is synthesized
depending on the demand for glucose and ATP
(energy).
• If both are present in relatively high amounts,
then the excess of insulin promotes glucose
conversion into glycogen for storage in liver
and muscle cells.
• In the synthesis of glycogen, one ATP is
required per glucose incorporated into the
polymeric branched structure of glycogen.
actually, glucose-6-phosphate is the cross-
roads compound.
• Glucose-6-phosphate is synthesized directly
from glucose or as the end product of
gluconeogenesis.
Glycogenesis Biosynthesis of Glycogen
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17. • In glycogenolysis, glycogen stored in the liver and muscles is converted first to glucose-1-
phosphate and then into glucose-6-phosphate.
• Two hormones which control glycogenolysis are a peptide, glucagon from the pancreas and
epinephrine from the adrenal glands.
• Glucagon is released from the pancreas in response to low blood glucose and epinephrine is
released in response to stress.
• Both hormones act upon enzymes to stimulate glycogen phosphorylase to begin glycogenolysis
and inhibit glycogen synthetase (to stop glycogenesis).
• Glycogen is a highly branched polymeric structure containing glucose as the basic monomer.
GLYCOGENOLYSIS
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18. • First individual glucose molecules
are hydrolyzed from the chain,
followed by the addition of a
phosphate group at C-1.
• In the next step, the phosphate is
moved to the C-6 position to give
glucose 6-phosphate.
• Glucose-6-phosphate converted to
glucose for distribution in the
blood to various cells such as
brain cells.
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19. Regulation of Blood glucose level
The balance of glucose is achieved by a negative feedback mechanism. The main hormone to
balance the glucose in the blood is insulin, glucagon, somatostatins and amylin.
1. Insulin: Insulin (formed in pancreatic beta cells) lowers blood glucose levels. Insulin is produced
by β cells of the islets of Langerhans. It regulates the metabolism of carbohydrates and fat,
enhances the entry of glucose in the cell, enhances the storage of glucose as glycogen and
enhances the synthesis of proteins, lipids, and amino acids. Finally, it produces hypoglycemia.
2. Glucagon: Glucagon is a hormone that the pancreas makes to help regulate blood glucose (sugar)
levels. Glucagon increases blood sugar levels and prevents them from dropping too low.
3. Epinephrine: also called adrenaline, is a hormone that is secreted by the adrenal glands. It causes
an increase in blood sugar and lactate due to the acceleration of glycogenolysis in the liver and
muscles. It diminishes the uptake of glucose by tissue cells, thus interfering with its utilization. It
also causes a reduction in the amount of insulin from the pancreas.
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20. 4. Anterior Pituitary Factors: Growth hormone released from the anterior pituitary gland. It is
regulated by the hypothalamus. It produces various changes in carbohydrate metabolism. They
cause inhibition of insulin action with decreased utilization of carbohydrates and lowering of the
respiratory quotient.
5. Thyroid Hormone: It is a hormone of the thyroid gland. Thyroxine elevates hepatic glycogenolysis
resulting in the rise of blood sugar levels.
6. Sex Hormones: Estrogens stimulate increased insulin secretion resulting in reduced blood sugar
levels. Testosterone also decreases blood sugar levels.
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21. Abnormal Metabolism of Carbohydrates
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22. • Hyperglycaemia is an abnormally high blood glucose (blood sugar) level –above 180-
200mg/dL.
• Conditions that can cause hyperglycaemia are diabetes, pancreatitis, Cushing’s syndrome,
unusual hormone-secreting tumours, pancreatic cancer, certain medications, and severe
illnesses.
• The main symptoms of hyperglycaemia are increased thirst and a frequent need to urinate.
HYPERGLYCAEMIA
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23. • Hypoglycemia also called low blood glucose or low blood sugar, occurs when the level of glucose
in the blood drops below normal, a level of 70 (mg/dL) or less.
• Symptoms: Sweaty, Hungry, Headachy, Blurred vision, Sleepy or tired, Confusion etc.
• The most common cause of hypoglycemia is medications used to treat diabetes mellitus such as
insulin and sulfonylureas.
• Risk is greater in diabetics who have eaten less than usual, exercised more than usual, or drunk
alcohol.
• Other causes of hypoglycaemia include kidney failure, certain tumours, liver disease,
hypothyroidism, starvation, severe infections, and a number of drugs including alcohol.
HYPOGLYCAEMIA
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24. • Glycosuria is the excretion of glucose into the urine. Ordinarily, urine contains no glucose because
the kidneys are able to reabsorb all of the filtered glucose from the tubular fluid back into the
bloodstream.
• Causes of Glycosuria: Diabetes mellitus, Hyperthyroidism, High-sugar diet
• Symptoms of Glycosuria: Abdominal pain, High blood sugar levels on testing in some cases, High
urine glucose levels, Excessive thirst.
GLYCOSURIA
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25. • Diabetes Mellitus (DM), commonly referred to as diabetes, is a group of metabolic diseases in which
there are high blood sugar levels over a prolonged period. Diabetes is due to either the pancreas not
producing enough insulin or the cells of the body not responding properly to the insulin produced.
• Symptoms of high blood sugar include frequent urination, increased thirst, and increased hunger.
• If left untreated, diabetes can cause many complications including heart disease, stroke, chronic kidney
failure, foot ulcers & damage to the eyes.
 Type 1 DM results from the pancreas's failure to produce enough insulin. This form was referred to as
“insulin-dependent diabetes mellitus" (IDDM) or "juvenile diabetes". The cause is unknown.
 Type 2 DM begins with insulin resistance, a condition in which cells fail to respond to insulin
properly. As the disease progresses a lack of insulin may also develop. This form was referred to as
“non-insulin-dependent diabetes mellitus" (NIDDM) or "adult-onset diabetes". The most common
cause is excessive body weight and not enough exercise.
DIABETES MELLITUS (DM)
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26. THANK
YOU
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