Digestion & Absorption of Carbohydrates 1- In the Mouth
Salivary amylase digests starch partially into mixtures of dextrins
and maltose. 2- In the Stomach Salivary amylase acts for short time
till the gastric HCL inhibits the enzyme (due to drop of pH). Small
amount of acid hydrolysis occurs in stomach. 3- In the Small
Intestine a- Pancreatic amylase It completes the digestion of
starch to maltose and isomaltose. b- Intestinal disaccharidases
They complete the action of other enzymes with production of
monosaccharides e.g. sucrase, maltase, lactase acting on sucrose,
maltose,lactose.
Slide 3
So, the end products of carbohydrate digestion are mainly
glucose, galactose and fructose. Monosaccharides are then absorbed
actively by small intestine. The portal vein carries simple sugars
to the liver where they are metabolized. Liver does not consume all
sugars passing through it, but a large proportion of these sugars
is deliverded to systemic blood in order to be utilized by other
tissues.
Slide 4
Summary Diagram for Fate of Absorbed Sugars Glucose Fructose
Galactose Oxidation Other carbohydrates Cholesterol & other
steroids Carbon skeleton of Amino acids Glycogen FA Glycerol
3-phosphate TAG Glycerophosphatides
Slide 5
OXIDATION OF GLUCOSE A- The Major Pathways for Oxidation which
are mainly concerned with energy production. I- Glycolysis: It
produces pyruvate under aerobic condition and lactate under
anaerobic condition. II- Citric acid cycle (Krebs cycle): Under
aerobic condition, pyruvate is converted to active acetate for
oxidation through citric acid cycle. B- The Minor Pathways for
Oxidation which are mainly for synthesis of other glucose
derivatives and not for energy production. I- Hexose monophosphate
pathway (HMP): For production of pentoses and NADPH. II- Uronic
acid pathway: For production of uronic acids.
Slide 6
A- The Major Pathways for Oxidation I-GLYCOLYSIS Sequence of
enzymatic reactions in which one molecule of glucose is converted
into two molecules of three carbon compound, either pyruvate in the
presence of oxygen or lactate in the absence of oxygen. Glycolytic
pathway proceeds in the cytosol of all cells (all of the enzymes of
glycolysis are found in the cytosol). Glycolysis is also termed
anaerobic oxidation of glucose as it can proceed in the absence of
oxygen.
Slide 7
Steps of Glycolysis can be divided into two phases: Phase I In
this preparatory stage, glucose is phosphorylated and cleaved to
yield two molecules of glyceraldehyde 3-phosphate. This process
consumes 2 ATP. Phase II The two molecules of glyceraldehyde
3-phosphate are converted to pyruvate under aerobic state with
generation of 4 ATP at substrate level and 6 ATP at the respiratory
chain level. Under anaerobic state only 4 ATP are formed at the
substrate level with conversion of pyruvate to lactate.
Slide 8
Regulation of Glycolysis: Glycolysis is regulated at three
nonequilibrium (irreversible) reactions, i.e. 3 key enzymes:
Glucokinase (or hexokinase), Phosphofructokinase-1 (PFK-1) Pyruvate
kinase (PK).
Slide 9
II- CITRIC ACID CYCLE (Tricarboxylic Acid Cycle or Krebs'
Cycle) It is formed of a series of reactions that are responsible
for the complete oxidation of the acetyl moiety of acetyl-CoA. It
is the final common pathway for the oxidation of carbohydrates,
lipids and proteins because glucose, fatty acids and most amino
acids are metabolized to acetyl-CoA or intermediates of the cycle.
During the oxidation of acetyl-CoA, coenzymes (NAD and FAD) are
reduced and subsequently reoxidized in the respiratory chain with
the formation of ATP.
Slide 10
Site: The enzymes of the TCA cycle are found in the
mitochondrial matrix except succinate dehydrogenase which is
tightly bound to the inner mitochondrial membrane (forms complex II
of the respiratory chain). The enzymes of the TCA cycle are in
close proximity to the enzymes of the respiratory chain.
Slide 11
B- The Minor Pathways for Oxidation I- Hexose Monophosphate
Pathway (HMP): The pentose phosphate pathway (PPP) is an
alternative route for glucose oxidation. It has two major
functions, formation of: 1) Ribose-5-p required for nucleotide and
nucleic acid synthesis 2) NADPH The enzymes of the pentose
phosphate pathway are cytosolic. HMP is active in certain tissues
e.g. liver, thyroid, adrenal cortex, adipose tissue, gonads,
retina, lactating mammary gland and RBCs.
Slide 12
NADPH is required for the following reactions: Reduction of
metabolically impotant compounds as glutathione and folic acid.
Synthesis of fatty acids Cholesterol synthesis Hydroxylation
reactions. Glutathione is of particular importance to combat
oxidation stress in tissues and to keep hemoglobin active by
conserving iron in ferrous state
Slide 13
II-Uronic Acid Pathway Uronic acid pathway is also an
alternative oxidative pathway for glucose that does not lead to the
formation of ATP. Uronic acid pathway is a cytosolic pathway that
occurs in the liver. In humans, it catalyzes the conversion of
glucose to glucuronic acid, and pentoses. Importance of Uronic acid
pathway The main function is the formation of UDP-glucuronate which
is utilized in the following pathways: Glycosaminoglycans (GAGs)
synthesis. Conjugation reactions with many compounds to increase
their water solubility such as: all steroid hormones and their
metabolites, bilirubin and certain detoxification reactions of
xenbiotics such as phenols.
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GLYCOGEN METABOLISM Glycogen is a highly branched polymer of
glucose. It is the main storage form of carbohydrates in animals.
It is present mainly in the liver and in muscles. Liver glycogen
(forms 8 10% of its wet weight) maintains blood glucose between
meals. After 1218 hours of fasting, liver glycogen is almost
totally depleted. Muscle glycogen (forms 2% of its wet weight)
:Muscle glycogen supplies the contracting muscles with a readily
available source of glucose.
Slide 15
Glycogen metabolism includes the following: I- GLYCOGENESIS
Glycogenesis is synthesis of glycogen from glucose-6-p.this
requires presence of the enzyme glycogen synthase. II-
GLYCOGENOLYSIS Glycogenolysis is breking-down of glycogen to
glucose (in the liver) or to g-6-p (in the muscle) Both
glycogenesis and glycogenolysis are under strict hormonal control
mediated by a second messenger cyclic AMP
Slide 16
GLUCONEOGENESIS It is the synthesis of glucose and /or glycogen
from non- carbohydrate precursors e.g. glycerol, glucogenic amino
acids and lactate. Its main function is to supply blood glucose in
case of carbohydrate deficiency (fasting, starvation and low
carbohydrate diet). It starts 4 to 6 hours after the last meal and
continues throughout fasting state.
Slide 17
REGULATION OF BLOOD GLUCOSE The normal fasting plasma glucose
level (after 8-12 hours fasting) is between 70 to less than 100
mg/dL, increases after meal and returns back to
Slide 18
After-meal rise in blood glucose stimulates insulin secretion
from pancreatic -cells of islets of langerhans. Insulin action: It
is secreted by the B-cells of pancreatic islets in response to
hyperglycemia. It produces its effects through the following
mechanisms: It increases the uptake of glucose by extrahepatic
tissues (heart, skeletal muscles and adipose tissues). It increases
utilization of glucose (oxidation, glycogenesis and lipogenesis) in
different tissues. It decreases output of glucose by liver
(decreases glycogenolysis and gluconeogenesis). During fasting
blood glucose decreases so insulin secretion is inhibited whereas
the anti-insulin hormones increase leading to activation of
mechanisms of glucose production: glycogenesis and
gluconeogenesis.
Slide 19
During fasting blood glucose decreases so insulin secretion is
inhibited whereas the anti-insulin hormones increase leading to
activation of mechanisms of glucose production: glycogenesis and
gluconeogenesis.
Slide 20
Diabetes Mellitus Definition The term diabetes mellitus
describes a metabolic disorder that is characterized by persistent
rise in blood glucose (hyperglycemia) result from defects in
insulin secretion, insulin action, or both. Classification of DM 1)
Type I Diabetes Mellitus Type I diabetes is primarily a disease of
the young. It was previously known as insulin dependent diabetes
mellitus (IDDM) means that it necessitates insulin to control
hyperglycaemia 2) Type II Diabetes Mellitus It is previously known
as noninsulin dependent diabetes mellitus (NIDDM) means that drugs
stimulate endogenous insulin secretion and promoting glucose
utilization are required.
Slide 21
Metabolic Changes in DM All the metabolic changes are due to
decrease in the insulin / anti- insulin ratio, which produces
changes reversal to insulin action or as a consequent of
hyperglycemia. 1) Changes in carbohydrate metabolism include: This
leads to hyperglycemia, glucosuria, polyuria, loss of electrolytes,
dehydration, and polydepsia. 2) Changes in lipid metabolism
include: Decreased lipogenesis and increased lipolysis. This leads
to weight loss and increases plasma free fatty acids. 3) Changes in
protein metabolism include: it leads to increased sensitivity to
infection and delayed healing of wounds.
Slide 22
Complications of DM: These complications can occur over a long
period of time. They can be divided in macrovascular and
microvascular complications. Diabetes accelerates atherosclerosis
that can lead to coronary artery disease, stroke and peripheral
vascular disease (macrovascular disease) Damage to the retina
(retinopathy), kidney (nephropathy) and nerves (neuropathy)
(microvascular disease).
Slide 23
Types of Diabetic Coma I- Diabetic Ketoacidosis: Diabetic
ketoacidosis is considered a medical emergency that results from
uncontrolled hyperglycemia and deficiency of insulin. The condition
can be precipitated by stress and infection. Diabetic ketoacidosis
is much more common in type I diabetes, but can also occur in
patients with type II diabetes. II- Hypoglycemic Coma Hypoglycemia
results from taking too much diabetes medication or insulin. It is
manifested as headache, feeling dizzy, poor concentration, tremors
of hands, and sweating are common symptoms of hypoglycemia. Coma
occurs if blood sugar level gets too low.
Slide 24
Diagnosis of DM: Many patients with diabetes remain
asymptomatic for long periods, so that the first presentation of
the disease is frequently a chronic complication. Symptoms include
polyuria, polydipsia, polyphagia, prolonged time of wound healing,
and weight loss. Polyphagia results from the decreased glucose
uptake by the satiety centre in the brain.
Slide 25
Tests for Diagnosis and Assessment of DM Control I- Fasting and
2-hour (post-glucose or postprandial) plasma glucose levels in an
oral glucose tolerance test (OGTT). Non-diabetic healthy subjects
will have: Fasting plasma glucose < 100 mg/dL, Two-hours value
in an OGTT (2-h PG) < 140 mg/dL. Patients with diabetes mellitus
will have: Fasting plasma glucose > 126 mg/dL, 2-hour value in
an OGTT (2-h PG) at or above 200 mg/dL. II- Oral Glucose Tolerance
Test (OGTT) Normal OGTT: There is an increase in plasma glucose
levels after 30 and 60 minutes from the glucose load due to the
absorption of glucose followed by a drop due to increased uptake
and utilization of glucose under the effect of the stimulated
insulin secretion. No glucosuria occurs during the test.
Slide 26
III- Measurement of Glycated- Hb (HbA 1C ): It is a good for
diagnosis and monitor of blood glucose to assess diabetic control
and to follow up of diabetic patients. Normal HBA 1C is 4 6.5%;
levels above 6.5% are diagnostic of diabetes mellitus and levels
> 8 % indicate poor diabetic control.
Slide 27
Treatment of Diabetes Mellitus Diet control It is to achieve
weight reduction in overweight patients with type II DM. If
improvement in hyperglycemia is not achieved by diet, trial with an
oral drug should be started. Oral Anti-diabetic Drugs: These drugs
are used for type II DM but not for type I DM oral hypoglycemic
drugs are: Drugs that increase insulin secretion, improve insulin
sensitivity or decrease the intestinal absorption of carbohydrates
and fats Insulin: Human insulin is now available in the market and
often it is preferred. It is injected subcutaneously, or as an
insulin pen. Recently, inhaled insulin is under trials.