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Carbohydrate (Unit-I) BSc Nursing
Lectured by :
Dr. Wazid Hassan, PhD
KIMSICON Hospital , Vizag, AP, INDIA
Biochemistry class
WHAT IS BIOCHEMISTRY ????
BIOCHEMISTRY (The chemistry of Life), Chemistry of Living
beings or Chemical Basis of Life.
‘Biochemistry is a branch of life science, which deals with the
study of biochemical reactions and processes occurring in living
cells of organisms.’
The German chemist Carl Neuberg have coined the term
Biochemistry in 1903
Medical and Diagnostic Biochemistry is a branch of Biochemistry
which deals with:
 Biochemical constituents of human body
 Their interactions in body cells
 To maintain normal health, growth and reproduction and
human related diseases.
Biochemical constituents of cell:
 Carbohydrates
 Lipids
 Proteins
 Enzymes
 Nucleic Acids
 Vitamins
 Minerals
 Water
To be study of
chemistry, properties ,
functions, metabolism
and related disorders
for disease.
What you Know about these biomolecules?
Carbohydrates
Lipids
Proteins
Enzymes
General definition
The main functions of carbohydrates are energy storage and
providing structure to the cells. Glucose is a most common sugar
(carbohydrate), but not all carbohydrates are sugars. The
carbohydrates are more on earth than any other known type of
biomolecule; they are used to store energy and genetic
information as well as play important roles in cell to cell
interaction and communication.
Carbohydrates chemically define
A carbohydrate is a biomolecule consisting of (C), (H) and (O) atoms,
usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus
with the empirical formula Cm(H2O)n (where m may or may not be
different from n) such as Glucose (C6H12O6). A common term
in biochemistry, ‘saccharide’ where it is a synonym of a group that
includes sugars, starch, and cellulose. The saccharides are divided into
four chemical groups monosaccharide, disaccharides, oligosaccharides,
and polysaccharides.
Class
(degree of polymerization)
Subgroup Components
Sugar (1–2)
Monosaccharides
Glucose, galactose, fructose,
xylose
Disaccharides
Sucrose, lactose, maltose, is
omaltulose, trehalose
Polyols Sorbitol, mannitol
Oligosaccharides (3–9)
Malto-oligosaccharides Maltodextrins
Other oligosaccharides
Raffinose, stachyose, fructo-
oligosaccharides
Polysaccharides (>9)
Starch
Amylose, amylopectin,
modified starches
Non-starch
polysaccharides
Glycogen, Cellulose, Hemicel
lulose, Pectins, Hydrocolloid
s
Classification of Carbohydrates
Cyclic and linear glucose (Monosaccharide)
Digestion of Carbohydrates
•The principal sites of carbohydrate digestion are the mouth and small
intestine. The dietary carbohydrate consists of:
•Polysaccharides: Starch, glycogen and cellulose
•Disaccharides: Sucrose, maltose and lactose
•Monosaccharides: Mainly glucose and fructose.
•Monosaccharides need no digestion prior to absorption, whereas
disaccharides and polysaccharides must be hydrolyzed to simple sugars
before their absorption.
• Digestion of carbohydrates begins in the mouth. Salivary glands secrete α-
amylase (ptylin), which initiates the hydrolysis of a starch.
•During mastication, salivary α-amylase acts briefly on dietary starch in
random manner breaking some α-(1 → 4) bonds, α-amylase hydrolyzes
starch into dextrins.
Carbohydrate digestion halts temporarily in the stomach because the
high acidity inactivates the salivary α-amylase.
Digestion in Intestine
•Further digestion of carbohydrates occurs in the small intestine by
pancreatic enzymes. There are two phases of intestinal digestion.
1.Digestion due to pancreatic α-amylase
2.Digestion due to intestinal enzymes : sucrase, maltase, lactase,
isomaltase
Carbohydrate Absorption
 Carbohydrates are mainly absorbed as monosaccharides.
 Only a small fraction is absorbed as disaccharides and almost none is absorbed
as larger carbohydrate compounds .
 About 80% of the absorbed monosaccharides are glucose.
 The remaining 20 percent of absorbed monosaccharides is composed almost
entirely of galactose and fructose—the galactose derived from milk and the
fructose as one of the monosaccharides digested from cane sugar.
 Virtually all the monosaccharides are absorbed by a secondary active transport
process.
 Glucose absorption occurs in a co-transport mode with active transport of
sodium.
 Galactose is transported by almost exactly the same mechanism as glucose.
Lactose intolerance
 It is the inability to digest lactose
due to the deficiency of Lactase
enzyme.
 Lactose, or milk sugar, is a
disaccharide composed of glucose
and galactose.
 Ingested lactose must be digested
before it can be absorbed, a task
accomplished by the intestinal
brush border enzyme lactase.
 Generally, lactase is found only in
juvenile mammals, except in some
humans of European descent.
Those people inherit a dominant
gene that allows them to produce
lactase after childhood.
Lactose intolerance cont..
 Scientists believe the lactase gene provided
a selective advantage to their ancestors,
who developed a culture in which milk and
milk products played an important role.
 In cultures in which dairy products are not
part of the diet after weaning, most adults
lack the gene and synthesize less intestinal
lactase.
 Decreased lactase activity is associated
with a condition known as lactose
intolerance. If a person with lactose
intolerance drinks milk or eats dairy
products, diarrhea may result. In addition,
bacteria in the large intestine ferment
lactose to gas and organic acids, leading to
bloating and flatulence.
 The simplest remedy is to remove
milk products from the diet, although
milk predigested with lactase is
Carbohydrate Metabolism
Metabolism: The sum of all the chemical changes occurring in a cell, a tissue, or
the body. Each metabolic pathway is composed of multi enzyme sequences, and
each enzyme, in turn, may exhibit important catalytic or regulatory features.
 Most pathways can be classified as either catabolic (degradative) or anabolic
(synthetic).
 Catabolic reactions break down complex molecules, such as proteins,
polysaccharides, and lipids, to a few simple molecules, for example, CO2, NH3
(ammonia), and water.
 Catabolism also allows molecules in the diet (or nutrient molecules stored in
cells) to be converted into building blocks needed for the synthesis of complex
molecules.
 Catabolic reactions serve to capture chemical energy in the form of adenosine
triphosphate (ATP) from the degradation of energy-rich fuel molecules.
 Anabolic pathways form complex end products from simple
precursors, for example, the synthesis of the polysaccharide,
glycogen, from glucose.
 Anabolic reactions combine small molecules, such as amino acids, to
form complex molecules, such as proteins
 Require energy (endergonic), which is generally provided by the
breakdown of ATP to adenosine diphosphate (ADP) and inorganic
phosphate (Pi).
 Anabolic reactions often involve chemical reductions in which the
reducing power is most frequently provided by the electron donor
NADPH.
Carbohydrate Metabolism Cont..
Figure :-Major Pathways in
Carbohydrate Metabolism
 Energy transforming pathways of carbohydrate metabolism include
glycolysis, glycogenesis, glycogenolysis, gluconeogenesis, and
pentose phosphate pathway
Glycolytic Pathway
Steps of Glycolysis
 Glycolysis is the sequence of 10 enzyme catalyzed reactions that converts glucose
into pyruvate with the simultaneous production of ATP.
 The first step in glycolysis is the conversion of D-glucose into glucose-6-phosphate.
The enzyme that catalyzes this reaction is hexokinase.
 The second reaction of glycolysis is the rearrangement of glucose 6-phosphate
(G6P) into fructose 6-phosphate (F6P) by glucose phosphate isomerase
(Phosphoglucose Isomerase).
 Phosphofructokinase, with magnesium as a cofactor, changes fructose 6-
phosphate into fructose 1,6-bisphosphate.
 The enzyme Aldolase splits fructose 1, 6-bisphosphate into two sugars that are
isomers of each other. These two sugars are dihydroxyacetone phosphate (DHAP)
and glyceraldehyde 3-phosphate (GAP).
 The enzyme triophosphate isomerase rapidly inter- converts the molecules
dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (GAP).
Glyceraldehyde phosphate is removed / used in next step of Glycolysis.
 Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) dehydrogenates and adds an
inorganic phosphate to glyceraldehyde 3-phosphate, producing 1,3-
bisphosphoglycerate.
 Phosphoglycerate kinase transfers a phosphate group from 1,3-
bisphosphoglycerate to ADP to form ATP and 3-phosphoglycerate.
 The enzyme phosphoglycero mutase relocates the P from 3- phosphoglycerate
from the 3rd carbon to the 2nd carbon to form 2-phosphoglycerate.
 The enzyme enolase removes a molecule of water from 2-phosphoglycerate to form
phosphoenolpyruvic acid (PEP).
 The enzyme pyruvate kinase transfers a P from phosphoenolpyruvate (PEP) to ADP
to form pyruvic acid and ATP Result in step 10.
 Although 2 ATP molecules are used in steps 1-3, 2 ATP molecules are generated in
step 7 and 2 more in step 10. This gives a total of 4 ATP molecules produced. If
you subtract the 2 ATP molecules used in steps 1-3 from the 4 generated at the
end of step 10, you end up with a net total of 2 ATP molecules produced.
 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 of Glycolysis cont…
Regulation of Glycolysis
The Fates of Pyruvate
 Pyruvic acid can be made from glucose through glycolysis, converted back to
carbohydrates (such as glucose) via gluconeogenesis, or to fatty acids through
acetyl-CoA.
 It can also be used to construct the amino acid alanine, and it can be
converted into ethanol.
 Pyruvic acid supplies energy to living cells through the citric acid cycle (also
known as the Krebs cycle) when oxygen is present (aerobic respiration); when
oxygen is lacking, it ferments to produce lactic acid.
 Pyruvate is an important chemical compound in biochemistry. It is the output
of the anaerobic metabolism of glucose known as glycolysis. One molecule of
glucose breaks down into two molecules of pyruvate, which are then used to
provide further energy in one of two ways.
 Pyruvate is converted into acetyl- coenzyme A, which is the main input for a
series of reactions known as the Krebs cycle.
The net reaction of converting pyruvate into acetyl CoA and CO2 is:
2 Pyruvate + 2NAD+ +2 CoA 2Acetyl CoA + NADH +2CO2
The Fates of Pyruvate Cont…
 Pyruvate is also converted to oxaloacetate by an anaplerotic reaction, which
replenishes Krebs cycle intermediates; also, oxaloacetate is used for
gluconeogenesis. These reactions are named after Hans Adolf Krebs, the
biochemist awarded the 1953 Nobel Prize for physiology, jointly with Fritz
Lipmann, for research into metabolic processes. The cycle is also known as the
citric acid cycle or tri-carboxylic acid cycle, because citric acid is one of the
intermediate compounds formed during the reactions.
 If insufficient oxygen is available, the acid is broken down anaerobically, creating
lactate in animals and ethanol in plants and microorganisms. Pyruvate from
glycolysis is converted by fermentation to lactate using the enzyme lactate
dehydrogenase and the coenzyme NADH in lactate fermentation. Alternatively it is
converted to acetaldehyde and then to ethanol in alcoholic fermentation.
 Pyruvate is a key intersection in the network of metabolic pathways. Pyruvate can
be converted into carbohydrates via gluconeogenesis, to fatty acids or energy
through acetyl-CoA, to the amino acid alanine, and to ethanol. Therefore, it unites
several key metabolic processes.
Glycosis
Citric Acid Cycle; The TCA Cycle
• Pyruvate (actually the acetyl group) from glycolysis is degraded to CO2
– The acetyl group is formed in stage II of metabolism from
carbohydrate and amino acid metabolism
• 1GTP (ATP in bacteria) and 1 FADH2 is produced during one turn of
the cycle
• 3 NADH are produced during one turn of the cycle
• NADH and FADH2 energize electron transport and oxidative
phosphorylation
• Eight reactions make up the Krebs cycle
– If you are given the name of the enzyme, you should be able to
draw the structure of the reactants and products
– You may be given the names of all eight reactions and will be
expected to reproduce the whole cycle
Where do all the NADH’s and FADH2’s Go
Metabolism of Carbohydrate
1. Glycolysis (Glucose to Pyruvate)
2. Gluconeogenesis (Reverse of Glycolysis/Pyruvate to Glucose)
3. Glycogenesis (Glucose to Glycogen)
4. Glycogenolysis (Glycogen to Glucose)
5. Pentose phosphate pathway (Glucose to Pentose and other
sugar)
1. Galactose and fructose disorders
• Galactosemia
• Hereditary fructose intolerance
2. Glycogen storage disorders
• GSD type I (von Gierke disease)
• GSD type II (Pompe disease )
3. Congenital disorders of glycosylation
Carbohydrate related Disorder
Regulation of Blood Glucose
Organ Used in controlled of Blood Sugar
Pancreas: One of the major players in glucose homeostasis, the pancreas releases
the hormones, insulin and glucagon, that control blood glucose. The cells in the
pancreas that produce insulin are called β (beta) cells and glucagon from α (alpha)
cells
Liver: This organ takes up glucose when levels are high and releases glucose when
levels are low. It stores glucose in chains as glycogen. It is key for glucose regulation.
Muscles: Our muscles are able to take up and store lots of glucose when insulin is
present. More muscles mass means more of a reservoir for glucose.
Fat cells: Fat cells take up glucose when insulin is present. Fat cells use glucose to
make more fat.
Brain: The brain takes up glucose whenever it needs energy, and doesn’t require
insulin. Glucose is the fuel the brain normally uses.
Hormones used in controlled of Blood Sugar
 INSULIN
 GLUCAGON
 It is a negative feedback process. The normal blood glucose level is 90mg per
100ml of blood. If the blood glucose levels get too high or too low, then the
changes are detected by the α and β cells in the islets of Langerhans.
 β cells act as receptors that detect a rise in blood glucose. When the rise is
detected they secrete insulin into the blood plasma. Insulin binds to glycoprotein
receptors on the cell surface of most body cells (notably excluding red blood
cells).
 Vesicles containing glucose carrier proteins are stimulated to move to, and fuse
with, the cell membrane. More glucose is taken up by the cell. Enzymes that
convert glucose to glycogen (and fat) are activated. Increased rate of conversion of
glucose to glycogen (glycogenesis) in the liver and muscles. This results in a
decrease in blood glucose levels.
 The α cells of the pancreas are act as receptors that detect a fall in blood glucose
level. When a fall is detected they secrete the hormone glucagon into the blood
plasma. Glucagon binds to glycoprotein receptors on LIVER cells only.
 When bound the following happens: An enzyme is activated that converts
glycogen to glucose (GLYCOGENOLYSIS). There is an increase in the conversion
of amino acids and glycerol into glucose (GLUCONEOGENESIS). This results in
an increase in blood glucose levels.
 There are a number of other hormones that increase blood sugar levels. The most
well known is adrenaline. Produced in adrenal glands (above kidneys). It raises
blood glucose by: Activating an enzyme that causes breakdown of glycogen to
glucose in the liver. Inactivating an enzyme that synthesises glycogen from
glucose.
Hormone interaction in regulating blood glucose
Uses negative feedback as both hormones work to keep blood glucose at
around 90mg per 100ml of blood. They are said to work antagonistically.
 Diabetes mellitus (DM), also known as simply diabetes, or hyperglycemia
is a group of metabolic diseases in which there are high blood sugar levels
over a prolonged period.
 Type-1 DM results from the body's failure to produce enough insulin. This
form was previously 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 previously referred to as "non insulin-
dependent diabetes mellitus" (NIDDM) or "adult-onset diabetes". The
primary cause is excessive body weight and not enough exercise.
Diabetes mellitus (DM)
Characteristics DM -Type 1 DM -Type 2
% of diabetic pop 5-10% 90%
Age of onseta Usually < 30 yr + some
adults
Usually > 40 + some obese
children
Pancreatic function Usually none Insulin is low, normal or
high
Pathogenesis Autoimmune process Defect in insulin secretion,
tissue resistance to insulin,
increased HGO
Family history Generally not strong Strong
Obesity Uncommon Common
History of ketoacidosis Often present Rare except in stress
Clinical presentation moderate to severe
symptoms: 3Ps, fatigue, wt
loss and ketoacidosis
Mild symptoms: Polyuria
and fatigue. Diagnosed on
routine physical
examination
Treatment Insulin, Diet
Exercise
Diet ,Exercise,
Oral antidiabetics, Insulin
Symptoms Of DM
Type 1 DM
- Polyuria
- Polydipsia
- Polyphagia
- Weight loss
- Weakness
- Dry skin
- Ketoacidosis
Type 2 DM
- Patients can be
asymptomatic
- Polyuria
- Polydipsia
- Polyphagia
- Fatigue
- Weight loss
- Most patients are
discovered while
performing urine glucose
screening
Management of diabetes
 Blood glucose monitoring guidelines. (frequency, and pre-
exercise values)
 Insulin therapy guidelines (including type, dosages, and
adjustment strategies, and correction dosages)
 List of other medications
 Guidelines for hypoglycemia recognition and treatment
 Guidelines for hyperglycemia recognition and treatment
 Dietary and exercise modification Regular complication
monitoring
 Self monitoring of blood glucose and try to control of BP and
lipid level.
DM Diagonosis
1. Glucosuria: To detect glucose in urine by a paper strip Semi-
quantitative, Normal kidney threshold for glucose is essential
2. Ketonuria: To detect ketonbodies in urine by a paper strip,
Semi-quantitative
3. Fasting glucose test: After fasting for at least 12 hours, a
person’s blood is drawn and tested for glucose. A healthy person
would have a fasting blood glucose level of about 80-90 mg/dL.
4. Random Blood glucose: Glucose blood concentration in
samples obtained at any time regardless the time of the last
meal
DM Diagonosis
5. Oral Glucose Tolerance Test: After measuring fasting
glucose, a person is given a glucose-rich drink. Blood is then
drawn at time intervals to see how that person’s body is
processing the glucose.
6. Glycosylated hemoglobin (HbA1C): HbA1C is formed by
condensation of glucose with free amino groups of the globin
component of hemoglobin. Normally it comprises 4-6% of the
total hemoglobin. Increase in the glucose blood concentration
increases the glycated hemoglobin fraction. HbA1C reflects the
glycemic state during the preceding 8-12 weeks.
7. Serum Fructosamine: Formed by glycosylation of serum
protein (mainly albumin). Since serum albumin has shorter half
life than hemoglobin, serum fructosamine reflects the glycemic
state in the preceding 2 weeks. Normal is 1.5 - 2.4 mmole/L
when serum albumin is 5 gm/dL
Oral Glucose Tolerance Test (OGTT)
• It is a laboratory method to check how the body breaks
down (metabolizes) blood sugar, and how quickly it is
cleared from the blood.
• The test usually used to test for diabetes, insulin resistance,
impaired beta cell function and reactive hypoglycemia.
• 75 -100 gm of glucose are given to the patient with 300 ml
of water after an overnight fast
• Blood samples are drawn 1, 2, and 3 hours after taking the
glucose
• This is a more accurate test for glucose utilization if the
fasting glucose is borderline
OGTT Preparation
The patient is instructed not to restrict carbohydrate intake in the days
or weeks before the test.
The test should not be done during an illness, as results may not reflect
the patient's glucose metabolism when healthy.
 Usually the OGTT is performed in the morning as glucose tolerance can
exhibit a diurnal rhythm with a significant decrease in the afternoon.
 The patient is instructed to fast (water is allowed) for 8–12 hours prior to
the tests
A zero time (baseline) blood sample is drawn.
OGTT Procedure
 The patient is then given a 75g of glucose in a 300 ml solution and drink
within a 5-minute time frame.
 Blood is drawn every 30 min for 2 hr to measure of glucose (blood
sugar), and sometimes insulin levels. The intervals and number of
samples vary according to the purpose of the test.
 For simple diabetes screening, the most important sample is the 2 hour
sample and the 0 and 2 hour samples may be the only ones collected.
Pre-diabetes
At this stage, blood glucose levels are higher than
normal after a meal and at a resting state, but not
high enough to be classified as full-blown type 2
diabetes. People with pre-diabetes are at increased
risk for type 2 diabetes.
Type 2 diabetes
Blood glucose levels are always high because of
high insulin resistance and/or low insulin levels.
Diabetes
More than
200 mg/dl
Between
140 mg/dl
and
200 mg/dl
Less than
140 mg/dl Normal
Blood glucose levels are well-regulated.
Oral Glucose Tolerance Test
(OGTT)
OGTT Indication
• A curve is plotted with the blood glucose levels on the vertical axis
against the time of collection on the horizontal axis.
• The curve so obtained is called glucose tolerance curve.
Laboratory Profile of a normal person after glucose take.
Sample Fasting 0 min. 30 min. 60 min. 90 min. 120 min. 150 min. 180 min.
Blood Glucose (mg/dl) 90 100 150 120 110 80 70
Urinary Glucose Nil nil Nil nil nil nil nil
Glucose Tolerance Curve
Time in minutes
Laboratory Profile of a diabetic person after glucose take.
Sample Fasting 0 min. 30 min. 60 min. 90 min. 120 min. 150 min. 180 min.
Blood Glucose (mg/dl) 200 225 350 300 275 250 225
Urinary Glucose + + + + + + +
Time in minutes
Normal person OGTT glucose curve:
 Fasting blood glucose (Zero hour sample)- is 90 mg /dl, which is
well within the normal range (Normal 60-100 mg/dl).
 There is rise of blood glucose after glucose load and the peak
value is observed at 1 hour. This is due to absorption of glucose
from the intestine.
 The blood glucose level return to the fasting level within 2hour.
 Glucose is not found in the urine samples.
Diabetic person OGTT glucose curve:
 Fasting blood glucose is higher than normal
 The highest value is attained at 1 hour to 1 hour 30 minutes.
 Glucose is found in almost all the urine samples.
 The blood glucose level does not return to the fasting level even
within 2hour 30 minutes.
MINI GTT: Now a days Mini GTT is performed. In this, only zero hour and
two hours samples are collected. Fasting blood sample is collected, after
that Glucose load is administered to the patients. Post glucose load
sample is collected after 2 hours.
GCT Glucose challenge test: Used to check pregnant women for signs
of gestational diabetes. It can be done at any time of day, not on an
empty stomach. The test involves 50- 75 g of glucose, with a reading after
one hour.
Extended GTT: An extended glucose tolerance test may be conducted to
detect cases of reactive hypoglycaemia or other abnormalities of glucose
metabolism with samples taken at 0, 30, 60, 90, 120, 150 and 180
minutes. The extended test may also be used to diagnose acromegaly
when samples are also taken for growth hormone levels.
INTRAVENOUS(IV) GTT:This is done in a situations where oral
administration is not feasible such as a person with malabsorption
syndrome and partial gastrectomy.
Types of GTT
Caused By:
 Taking too much insulin.
 Not eating enough carbs for how much insulin patient take.
 Timing of when patients take their insulin.
 The amount and timing of physical activity.
 Drinking alcohol.
 How much fat, protein, and fiber are in patient meal.
 Hot and humid weather.
 Unexpected changes in your schedule.
 Other Medicine
What is ?????
Hypoglycemia is a condition in which patient blood sugar (glucose) level is lower than
the standard range. Glucose is our body's main energy source. Hypoglycemia is often
related to diabetes treatment. But other drugs and a variety of conditions is rare, it can
cause low blood sugar in people who don't have diabetes. Confusion, heart palpitations,
shakiness and anxiety are symptoms.
Hypoglycemia

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Carbohydrate Unit -I.pdf

  • 1. Carbohydrate (Unit-I) BSc Nursing Lectured by : Dr. Wazid Hassan, PhD KIMSICON Hospital , Vizag, AP, INDIA Biochemistry class
  • 2. WHAT IS BIOCHEMISTRY ???? BIOCHEMISTRY (The chemistry of Life), Chemistry of Living beings or Chemical Basis of Life. ‘Biochemistry is a branch of life science, which deals with the study of biochemical reactions and processes occurring in living cells of organisms.’ The German chemist Carl Neuberg have coined the term Biochemistry in 1903 Medical and Diagnostic Biochemistry is a branch of Biochemistry which deals with:  Biochemical constituents of human body  Their interactions in body cells  To maintain normal health, growth and reproduction and human related diseases.
  • 3. Biochemical constituents of cell:  Carbohydrates  Lipids  Proteins  Enzymes  Nucleic Acids  Vitamins  Minerals  Water To be study of chemistry, properties , functions, metabolism and related disorders for disease. What you Know about these biomolecules? Carbohydrates Lipids Proteins Enzymes
  • 4. General definition The main functions of carbohydrates are energy storage and providing structure to the cells. Glucose is a most common sugar (carbohydrate), but not all carbohydrates are sugars. The carbohydrates are more on earth than any other known type of biomolecule; they are used to store energy and genetic information as well as play important roles in cell to cell interaction and communication. Carbohydrates chemically define A carbohydrate is a biomolecule consisting of (C), (H) and (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula Cm(H2O)n (where m may or may not be different from n) such as Glucose (C6H12O6). A common term in biochemistry, ‘saccharide’ where it is a synonym of a group that includes sugars, starch, and cellulose. The saccharides are divided into four chemical groups monosaccharide, disaccharides, oligosaccharides, and polysaccharides.
  • 5. Class (degree of polymerization) Subgroup Components Sugar (1–2) Monosaccharides Glucose, galactose, fructose, xylose Disaccharides Sucrose, lactose, maltose, is omaltulose, trehalose Polyols Sorbitol, mannitol Oligosaccharides (3–9) Malto-oligosaccharides Maltodextrins Other oligosaccharides Raffinose, stachyose, fructo- oligosaccharides Polysaccharides (>9) Starch Amylose, amylopectin, modified starches Non-starch polysaccharides Glycogen, Cellulose, Hemicel lulose, Pectins, Hydrocolloid s Classification of Carbohydrates
  • 6. Cyclic and linear glucose (Monosaccharide)
  • 7.
  • 8. Digestion of Carbohydrates •The principal sites of carbohydrate digestion are the mouth and small intestine. The dietary carbohydrate consists of: •Polysaccharides: Starch, glycogen and cellulose •Disaccharides: Sucrose, maltose and lactose •Monosaccharides: Mainly glucose and fructose. •Monosaccharides need no digestion prior to absorption, whereas disaccharides and polysaccharides must be hydrolyzed to simple sugars before their absorption. • Digestion of carbohydrates begins in the mouth. Salivary glands secrete α- amylase (ptylin), which initiates the hydrolysis of a starch. •During mastication, salivary α-amylase acts briefly on dietary starch in random manner breaking some α-(1 → 4) bonds, α-amylase hydrolyzes starch into dextrins. Carbohydrate digestion halts temporarily in the stomach because the high acidity inactivates the salivary α-amylase. Digestion in Intestine •Further digestion of carbohydrates occurs in the small intestine by pancreatic enzymes. There are two phases of intestinal digestion. 1.Digestion due to pancreatic α-amylase 2.Digestion due to intestinal enzymes : sucrase, maltase, lactase, isomaltase
  • 9.
  • 10. Carbohydrate Absorption  Carbohydrates are mainly absorbed as monosaccharides.  Only a small fraction is absorbed as disaccharides and almost none is absorbed as larger carbohydrate compounds .  About 80% of the absorbed monosaccharides are glucose.  The remaining 20 percent of absorbed monosaccharides is composed almost entirely of galactose and fructose—the galactose derived from milk and the fructose as one of the monosaccharides digested from cane sugar.  Virtually all the monosaccharides are absorbed by a secondary active transport process.  Glucose absorption occurs in a co-transport mode with active transport of sodium.  Galactose is transported by almost exactly the same mechanism as glucose.
  • 11. Lactose intolerance  It is the inability to digest lactose due to the deficiency of Lactase enzyme.  Lactose, or milk sugar, is a disaccharide composed of glucose and galactose.  Ingested lactose must be digested before it can be absorbed, a task accomplished by the intestinal brush border enzyme lactase.  Generally, lactase is found only in juvenile mammals, except in some humans of European descent. Those people inherit a dominant gene that allows them to produce lactase after childhood.
  • 12. Lactose intolerance cont..  Scientists believe the lactase gene provided a selective advantage to their ancestors, who developed a culture in which milk and milk products played an important role.  In cultures in which dairy products are not part of the diet after weaning, most adults lack the gene and synthesize less intestinal lactase.  Decreased lactase activity is associated with a condition known as lactose intolerance. If a person with lactose intolerance drinks milk or eats dairy products, diarrhea may result. In addition, bacteria in the large intestine ferment lactose to gas and organic acids, leading to bloating and flatulence.  The simplest remedy is to remove milk products from the diet, although milk predigested with lactase is
  • 13. Carbohydrate Metabolism Metabolism: The sum of all the chemical changes occurring in a cell, a tissue, or the body. Each metabolic pathway is composed of multi enzyme sequences, and each enzyme, in turn, may exhibit important catalytic or regulatory features.  Most pathways can be classified as either catabolic (degradative) or anabolic (synthetic).  Catabolic reactions break down complex molecules, such as proteins, polysaccharides, and lipids, to a few simple molecules, for example, CO2, NH3 (ammonia), and water.  Catabolism also allows molecules in the diet (or nutrient molecules stored in cells) to be converted into building blocks needed for the synthesis of complex molecules.  Catabolic reactions serve to capture chemical energy in the form of adenosine triphosphate (ATP) from the degradation of energy-rich fuel molecules.
  • 14.  Anabolic pathways form complex end products from simple precursors, for example, the synthesis of the polysaccharide, glycogen, from glucose.  Anabolic reactions combine small molecules, such as amino acids, to form complex molecules, such as proteins  Require energy (endergonic), which is generally provided by the breakdown of ATP to adenosine diphosphate (ADP) and inorganic phosphate (Pi).  Anabolic reactions often involve chemical reductions in which the reducing power is most frequently provided by the electron donor NADPH. Carbohydrate Metabolism Cont..
  • 15.
  • 16. Figure :-Major Pathways in Carbohydrate Metabolism  Energy transforming pathways of carbohydrate metabolism include glycolysis, glycogenesis, glycogenolysis, gluconeogenesis, and pentose phosphate pathway
  • 17.
  • 19.
  • 20. Steps of Glycolysis  Glycolysis is the sequence of 10 enzyme catalyzed reactions that converts glucose into pyruvate with the simultaneous production of ATP.  The first step in glycolysis is the conversion of D-glucose into glucose-6-phosphate. The enzyme that catalyzes this reaction is hexokinase.  The second reaction of glycolysis is the rearrangement of glucose 6-phosphate (G6P) into fructose 6-phosphate (F6P) by glucose phosphate isomerase (Phosphoglucose Isomerase).  Phosphofructokinase, with magnesium as a cofactor, changes fructose 6- phosphate into fructose 1,6-bisphosphate.  The enzyme Aldolase splits fructose 1, 6-bisphosphate into two sugars that are isomers of each other. These two sugars are dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (GAP).  The enzyme triophosphate isomerase rapidly inter- converts the molecules dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (GAP). Glyceraldehyde phosphate is removed / used in next step of Glycolysis.  Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) dehydrogenates and adds an inorganic phosphate to glyceraldehyde 3-phosphate, producing 1,3- bisphosphoglycerate.
  • 21.  Phosphoglycerate kinase transfers a phosphate group from 1,3- bisphosphoglycerate to ADP to form ATP and 3-phosphoglycerate.  The enzyme phosphoglycero mutase relocates the P from 3- phosphoglycerate from the 3rd carbon to the 2nd carbon to form 2-phosphoglycerate.  The enzyme enolase removes a molecule of water from 2-phosphoglycerate to form phosphoenolpyruvic acid (PEP).  The enzyme pyruvate kinase transfers a P from phosphoenolpyruvate (PEP) to ADP to form pyruvic acid and ATP Result in step 10.  Although 2 ATP molecules are used in steps 1-3, 2 ATP molecules are generated in step 7 and 2 more in step 10. This gives a total of 4 ATP molecules produced. If you subtract the 2 ATP molecules used in steps 1-3 from the 4 generated at the end of step 10, you end up with a net total of 2 ATP molecules produced.  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 of Glycolysis cont…
  • 23. The Fates of Pyruvate  Pyruvic acid can be made from glucose through glycolysis, converted back to carbohydrates (such as glucose) via gluconeogenesis, or to fatty acids through acetyl-CoA.  It can also be used to construct the amino acid alanine, and it can be converted into ethanol.  Pyruvic acid supplies energy to living cells through the citric acid cycle (also known as the Krebs cycle) when oxygen is present (aerobic respiration); when oxygen is lacking, it ferments to produce lactic acid.  Pyruvate is an important chemical compound in biochemistry. It is the output of the anaerobic metabolism of glucose known as glycolysis. One molecule of glucose breaks down into two molecules of pyruvate, which are then used to provide further energy in one of two ways.  Pyruvate is converted into acetyl- coenzyme A, which is the main input for a series of reactions known as the Krebs cycle. The net reaction of converting pyruvate into acetyl CoA and CO2 is: 2 Pyruvate + 2NAD+ +2 CoA 2Acetyl CoA + NADH +2CO2
  • 24. The Fates of Pyruvate Cont…  Pyruvate is also converted to oxaloacetate by an anaplerotic reaction, which replenishes Krebs cycle intermediates; also, oxaloacetate is used for gluconeogenesis. These reactions are named after Hans Adolf Krebs, the biochemist awarded the 1953 Nobel Prize for physiology, jointly with Fritz Lipmann, for research into metabolic processes. The cycle is also known as the citric acid cycle or tri-carboxylic acid cycle, because citric acid is one of the intermediate compounds formed during the reactions.  If insufficient oxygen is available, the acid is broken down anaerobically, creating lactate in animals and ethanol in plants and microorganisms. Pyruvate from glycolysis is converted by fermentation to lactate using the enzyme lactate dehydrogenase and the coenzyme NADH in lactate fermentation. Alternatively it is converted to acetaldehyde and then to ethanol in alcoholic fermentation.  Pyruvate is a key intersection in the network of metabolic pathways. Pyruvate can be converted into carbohydrates via gluconeogenesis, to fatty acids or energy through acetyl-CoA, to the amino acid alanine, and to ethanol. Therefore, it unites several key metabolic processes.
  • 26. Citric Acid Cycle; The TCA Cycle • Pyruvate (actually the acetyl group) from glycolysis is degraded to CO2 – The acetyl group is formed in stage II of metabolism from carbohydrate and amino acid metabolism • 1GTP (ATP in bacteria) and 1 FADH2 is produced during one turn of the cycle • 3 NADH are produced during one turn of the cycle • NADH and FADH2 energize electron transport and oxidative phosphorylation • Eight reactions make up the Krebs cycle – If you are given the name of the enzyme, you should be able to draw the structure of the reactants and products – You may be given the names of all eight reactions and will be expected to reproduce the whole cycle
  • 27. Where do all the NADH’s and FADH2’s Go
  • 28. Metabolism of Carbohydrate 1. Glycolysis (Glucose to Pyruvate) 2. Gluconeogenesis (Reverse of Glycolysis/Pyruvate to Glucose) 3. Glycogenesis (Glucose to Glycogen) 4. Glycogenolysis (Glycogen to Glucose) 5. Pentose phosphate pathway (Glucose to Pentose and other sugar)
  • 29. 1. Galactose and fructose disorders • Galactosemia • Hereditary fructose intolerance 2. Glycogen storage disorders • GSD type I (von Gierke disease) • GSD type II (Pompe disease ) 3. Congenital disorders of glycosylation Carbohydrate related Disorder
  • 30. Regulation of Blood Glucose Organ Used in controlled of Blood Sugar Pancreas: One of the major players in glucose homeostasis, the pancreas releases the hormones, insulin and glucagon, that control blood glucose. The cells in the pancreas that produce insulin are called β (beta) cells and glucagon from α (alpha) cells Liver: This organ takes up glucose when levels are high and releases glucose when levels are low. It stores glucose in chains as glycogen. It is key for glucose regulation. Muscles: Our muscles are able to take up and store lots of glucose when insulin is present. More muscles mass means more of a reservoir for glucose. Fat cells: Fat cells take up glucose when insulin is present. Fat cells use glucose to make more fat. Brain: The brain takes up glucose whenever it needs energy, and doesn’t require insulin. Glucose is the fuel the brain normally uses.
  • 31. Hormones used in controlled of Blood Sugar  INSULIN  GLUCAGON
  • 32.  It is a negative feedback process. The normal blood glucose level is 90mg per 100ml of blood. If the blood glucose levels get too high or too low, then the changes are detected by the α and β cells in the islets of Langerhans.  β cells act as receptors that detect a rise in blood glucose. When the rise is detected they secrete insulin into the blood plasma. Insulin binds to glycoprotein receptors on the cell surface of most body cells (notably excluding red blood cells).  Vesicles containing glucose carrier proteins are stimulated to move to, and fuse with, the cell membrane. More glucose is taken up by the cell. Enzymes that convert glucose to glycogen (and fat) are activated. Increased rate of conversion of glucose to glycogen (glycogenesis) in the liver and muscles. This results in a decrease in blood glucose levels.  The α cells of the pancreas are act as receptors that detect a fall in blood glucose level. When a fall is detected they secrete the hormone glucagon into the blood plasma. Glucagon binds to glycoprotein receptors on LIVER cells only.  When bound the following happens: An enzyme is activated that converts glycogen to glucose (GLYCOGENOLYSIS). There is an increase in the conversion of amino acids and glycerol into glucose (GLUCONEOGENESIS). This results in an increase in blood glucose levels.  There are a number of other hormones that increase blood sugar levels. The most well known is adrenaline. Produced in adrenal glands (above kidneys). It raises blood glucose by: Activating an enzyme that causes breakdown of glycogen to glucose in the liver. Inactivating an enzyme that synthesises glycogen from glucose.
  • 33. Hormone interaction in regulating blood glucose Uses negative feedback as both hormones work to keep blood glucose at around 90mg per 100ml of blood. They are said to work antagonistically.
  • 34.  Diabetes mellitus (DM), also known as simply diabetes, or hyperglycemia is a group of metabolic diseases in which there are high blood sugar levels over a prolonged period.  Type-1 DM results from the body's failure to produce enough insulin. This form was previously 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 previously referred to as "non insulin- dependent diabetes mellitus" (NIDDM) or "adult-onset diabetes". The primary cause is excessive body weight and not enough exercise. Diabetes mellitus (DM)
  • 35. Characteristics DM -Type 1 DM -Type 2 % of diabetic pop 5-10% 90% Age of onseta Usually < 30 yr + some adults Usually > 40 + some obese children Pancreatic function Usually none Insulin is low, normal or high Pathogenesis Autoimmune process Defect in insulin secretion, tissue resistance to insulin, increased HGO Family history Generally not strong Strong Obesity Uncommon Common History of ketoacidosis Often present Rare except in stress Clinical presentation moderate to severe symptoms: 3Ps, fatigue, wt loss and ketoacidosis Mild symptoms: Polyuria and fatigue. Diagnosed on routine physical examination Treatment Insulin, Diet Exercise Diet ,Exercise, Oral antidiabetics, Insulin
  • 36. Symptoms Of DM Type 1 DM - Polyuria - Polydipsia - Polyphagia - Weight loss - Weakness - Dry skin - Ketoacidosis Type 2 DM - Patients can be asymptomatic - Polyuria - Polydipsia - Polyphagia - Fatigue - Weight loss - Most patients are discovered while performing urine glucose screening
  • 37. Management of diabetes  Blood glucose monitoring guidelines. (frequency, and pre- exercise values)  Insulin therapy guidelines (including type, dosages, and adjustment strategies, and correction dosages)  List of other medications  Guidelines for hypoglycemia recognition and treatment  Guidelines for hyperglycemia recognition and treatment  Dietary and exercise modification Regular complication monitoring  Self monitoring of blood glucose and try to control of BP and lipid level.
  • 38. DM Diagonosis 1. Glucosuria: To detect glucose in urine by a paper strip Semi- quantitative, Normal kidney threshold for glucose is essential 2. Ketonuria: To detect ketonbodies in urine by a paper strip, Semi-quantitative 3. Fasting glucose test: After fasting for at least 12 hours, a person’s blood is drawn and tested for glucose. A healthy person would have a fasting blood glucose level of about 80-90 mg/dL. 4. Random Blood glucose: Glucose blood concentration in samples obtained at any time regardless the time of the last meal
  • 39. DM Diagonosis 5. Oral Glucose Tolerance Test: After measuring fasting glucose, a person is given a glucose-rich drink. Blood is then drawn at time intervals to see how that person’s body is processing the glucose. 6. Glycosylated hemoglobin (HbA1C): HbA1C is formed by condensation of glucose with free amino groups of the globin component of hemoglobin. Normally it comprises 4-6% of the total hemoglobin. Increase in the glucose blood concentration increases the glycated hemoglobin fraction. HbA1C reflects the glycemic state during the preceding 8-12 weeks. 7. Serum Fructosamine: Formed by glycosylation of serum protein (mainly albumin). Since serum albumin has shorter half life than hemoglobin, serum fructosamine reflects the glycemic state in the preceding 2 weeks. Normal is 1.5 - 2.4 mmole/L when serum albumin is 5 gm/dL
  • 40. Oral Glucose Tolerance Test (OGTT) • It is a laboratory method to check how the body breaks down (metabolizes) blood sugar, and how quickly it is cleared from the blood. • The test usually used to test for diabetes, insulin resistance, impaired beta cell function and reactive hypoglycemia. • 75 -100 gm of glucose are given to the patient with 300 ml of water after an overnight fast • Blood samples are drawn 1, 2, and 3 hours after taking the glucose • This is a more accurate test for glucose utilization if the fasting glucose is borderline
  • 41. OGTT Preparation The patient is instructed not to restrict carbohydrate intake in the days or weeks before the test. The test should not be done during an illness, as results may not reflect the patient's glucose metabolism when healthy.  Usually the OGTT is performed in the morning as glucose tolerance can exhibit a diurnal rhythm with a significant decrease in the afternoon.  The patient is instructed to fast (water is allowed) for 8–12 hours prior to the tests A zero time (baseline) blood sample is drawn. OGTT Procedure  The patient is then given a 75g of glucose in a 300 ml solution and drink within a 5-minute time frame.  Blood is drawn every 30 min for 2 hr to measure of glucose (blood sugar), and sometimes insulin levels. The intervals and number of samples vary according to the purpose of the test.  For simple diabetes screening, the most important sample is the 2 hour sample and the 0 and 2 hour samples may be the only ones collected.
  • 42. Pre-diabetes At this stage, blood glucose levels are higher than normal after a meal and at a resting state, but not high enough to be classified as full-blown type 2 diabetes. People with pre-diabetes are at increased risk for type 2 diabetes. Type 2 diabetes Blood glucose levels are always high because of high insulin resistance and/or low insulin levels. Diabetes More than 200 mg/dl Between 140 mg/dl and 200 mg/dl Less than 140 mg/dl Normal Blood glucose levels are well-regulated. Oral Glucose Tolerance Test (OGTT) OGTT Indication
  • 43. • A curve is plotted with the blood glucose levels on the vertical axis against the time of collection on the horizontal axis. • The curve so obtained is called glucose tolerance curve. Laboratory Profile of a normal person after glucose take. Sample Fasting 0 min. 30 min. 60 min. 90 min. 120 min. 150 min. 180 min. Blood Glucose (mg/dl) 90 100 150 120 110 80 70 Urinary Glucose Nil nil Nil nil nil nil nil Glucose Tolerance Curve Time in minutes
  • 44. Laboratory Profile of a diabetic person after glucose take. Sample Fasting 0 min. 30 min. 60 min. 90 min. 120 min. 150 min. 180 min. Blood Glucose (mg/dl) 200 225 350 300 275 250 225 Urinary Glucose + + + + + + + Time in minutes
  • 45. Normal person OGTT glucose curve:  Fasting blood glucose (Zero hour sample)- is 90 mg /dl, which is well within the normal range (Normal 60-100 mg/dl).  There is rise of blood glucose after glucose load and the peak value is observed at 1 hour. This is due to absorption of glucose from the intestine.  The blood glucose level return to the fasting level within 2hour.  Glucose is not found in the urine samples. Diabetic person OGTT glucose curve:  Fasting blood glucose is higher than normal  The highest value is attained at 1 hour to 1 hour 30 minutes.  Glucose is found in almost all the urine samples.  The blood glucose level does not return to the fasting level even within 2hour 30 minutes.
  • 46. MINI GTT: Now a days Mini GTT is performed. In this, only zero hour and two hours samples are collected. Fasting blood sample is collected, after that Glucose load is administered to the patients. Post glucose load sample is collected after 2 hours. GCT Glucose challenge test: Used to check pregnant women for signs of gestational diabetes. It can be done at any time of day, not on an empty stomach. The test involves 50- 75 g of glucose, with a reading after one hour. Extended GTT: An extended glucose tolerance test may be conducted to detect cases of reactive hypoglycaemia or other abnormalities of glucose metabolism with samples taken at 0, 30, 60, 90, 120, 150 and 180 minutes. The extended test may also be used to diagnose acromegaly when samples are also taken for growth hormone levels. INTRAVENOUS(IV) GTT:This is done in a situations where oral administration is not feasible such as a person with malabsorption syndrome and partial gastrectomy. Types of GTT
  • 47. Caused By:  Taking too much insulin.  Not eating enough carbs for how much insulin patient take.  Timing of when patients take their insulin.  The amount and timing of physical activity.  Drinking alcohol.  How much fat, protein, and fiber are in patient meal.  Hot and humid weather.  Unexpected changes in your schedule.  Other Medicine What is ????? Hypoglycemia is a condition in which patient blood sugar (glucose) level is lower than the standard range. Glucose is our body's main energy source. Hypoglycemia is often related to diabetes treatment. But other drugs and a variety of conditions is rare, it can cause low blood sugar in people who don't have diabetes. Confusion, heart palpitations, shakiness and anxiety are symptoms. Hypoglycemia