Carbohydrates

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• Carbohydrates
• Part 1

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Introduction

• Organisms rely on the oxidation of complex
  organic compounds to obtain energy
• Three general types of such compounds are
• Carbohydrates (CHO)
• Amino acids
• And lipids
• CHO are the primary source of energy for brain,
  erythrocytes and retinal cells
• Stored primarily as liver muscle glycogen

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Carbohydrates CHO

• Compounds containing C, H, O
• General formula (CH2O)n
• All CHO contain CO and OH functional groups
• There are some derivatives of this formula
  (addition of phosphates, amines)
• Classification of CHO is based on four different
  properties
• The size of the base carbon chain
• The location of the CO functional group
• The number of sugar units
• The stereochemistry of the compound

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1- The size of the base carbon chain

• Can be classified based on the number of carbons
  in the molecule
• Trioses ( 3 Carbons)
• Tetroses
• Pentoses
• And hexoses
• The smallest CHO is glyceraldehyde ( 3
  Carbon)

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The location of the CO functional group

• Hydrates of aldehyde or ketone derivatives based
  on the location of the CO functional group
• Aldose form aldehyde as functional group
• Ketose form ketone as functional group

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3- The number of sugar units

• Classification based on the number of sugar units
  in the chain
• Monosaccharide
• Disaccharide (2 sugars linked together)
• Oligosaccharide (2 10 linked sugars)
• Polysaccharide (Long sugar chains)

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Monosaccharides

• Simplest sugars cannot be broken down into any
  simpler sugar
• 3 carbons triose, 4 carbons tetraose, 5
  carbons pentose, 6 carbons hexose
• Important pentose (5 carbon) sugars include
  ribose and 2-deoxyribose

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Disaccharides

• Formed from two monosaccharide with the
  production of water.
• Most common form is sucrose (table sugar), which
  is glucose and fructose
• Other forms include
• Lactose (glucose and galatose)
• and maltose (glucose and glucose)

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Common Disaccharides
Glucose Glucose
Glucose Galactose
Glucose Fructose
Sucrose ( table sugar )
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Polysaccharides

• Plants (cellulose) not digested by humans.
• Starch principle CHO (polysaccharide) storage
  product of plants
• Glycogen principle CHO storage product in
  animal.
• Formed by the combination of monosaccharide.

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4- Sterochemistry

• Mirror image forms
• D right side OH, L left side OH
• D L designations are based on the configuration
  about the single asymmetric C

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Glucose Metabolism

• Glucose is a primary source of energy.
• Various tissues and muscles throughout the body
  depend on glucose from the surrounding
  extracellular fluid for energy.
• Nervous tissue cannot concentrate or store CHO,
  critical to maintain steady supply
• If glucose levels fall below certain levels the
  nervous tissue lose its primary energy source and
  is incapable of maintaining normal function.

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Fate of glucose

• CHO is digested (starch and glycogen).
• Amylase digest the nonabsorbable forms of CHO to
  dextrin and disaccharide which are hydrolyzed to
  monosaccharide.
• Maltase is an enzyme released by intestinal
  mucosa that hydrolze maltose to two glucose units
• Sucrase hydrolyze sucrose to glucose fructose
• Lactase hydrolyze lactose to glucose galatose.

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Fate of glucose

• Disaccharides are converted into monosaccharide
  absorbed by the gut transported to the liver by
  the hepatic portal venous blood supply.
• Glucose is the only CHO to be directly used for
  energy or stored as glycogen.
• Others (galactose fructose) have to be
  converted to glucose before they can be used

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Lactose intolerance

• Lactose intolerance due to a deficiency of
  lactase enzyme on or in the intestinal lumens,
  which is needed to metabolize lactose.
• Results in an accumulation of lactose in stomach
  as waste lactic acid- causing the stomach upset
  and discomfort.

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Fate of glucose

• After glucose enters the cell it can go into one
  of three metabolic pathways based on
• availability of substrate and
• nutritional status of cell.
• Ultimate goal is to convert glucose to CO2 and
  H2O.
• During this process the cell obtains the
  high-energy molecule (ATP) from (ADP).

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Glucose metabolism

• 1st step in all pathways Glucose is converted to
  glucose -6 phosphate using ATP- catalyzed by
  hexokinase.
• Glucose-6- phosphate enters the pathways
• Embden-Meyerhof pathway
• Hexose Monophosphate shunt
• Glucogenesis (storage of glucose as glycogen)

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Glucose metabolism

• Embden-Meyerhof pathway
• glucose is broken down into two, three-carbon
  molecules of pyruvic acid that can enter the
  tricarboxylic acid cycle (TCA cycle) on
  conversion to acetyl-coenzyme A (acetyl-CoA).
• Hexose Monophosphate shunt
• The principal functions of the pathway are the
  production of
• deoxyribose and ribose sugars for nucleic-acid
  synthesis
• the generation of reducing power in the form of
  NADPH for fatty-acid and/or steroid synthesis

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Pathways in glucose metabolism

• Major energy pathways involved either directly or
  indirectly with glucose metabolism
• Glycolysis
• Breakdown of glucose for energy production
• Glycogenesis
• Excess glucose is converted and stored as
  glycogen
• High concentrations of glycogen in liver and
  skeletal muscle
• Glycogen is a quickly accessible storage form of
  glucose
• Glycogenolysis
• Breakdown of glycogen into glucose
• Glycogenolysis occurs when plasma glucose is
  decreased
• Occurs quickly if additional glucose is needed

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Pathways in glucose metabolism

• Gluconeogenesis
• Conversion of non-carbohydrate carbon substrates
  to glucose
• Gluconeogenesis takes place mainly in the liver
• Lipogenesis
• Conversion of carbohydrates into fatty acids
• Fat is another energy storage form, but not as
  quickly accessible as glycogen
• Lipolysis
• Decomposition of fat

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Regulation of Carbohydrate Metabolism

• The liver, pancreas, and other endocrine glands
  are all involved in controlling the blood glucose
  concentrations within a narrow range
• During a brief fast, glucose is supplied to the
  ECF from the liver through glycogenolysis.
• When the fasting period is longer than 1 day,
  glucose is synthesized from other sources through
  gluconeogenesis.
• Control of blood glucose is under two major
  hormones insulin and glucagon, both produced by
  the pancreas

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Regulation of Carbohydrate Metabolism

• Other hormones also exert some control over blood
  glucose concentrations
• As needed hormones regulate release of glucose.
• Hormones work together to meet 3 requirements
• Steady supply of glucose.
• Store excess glucose
• Use stored glucose as needed

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Insulin

• Primary hormone responsible for the entry of
  glucose into the cell.
• Synthesized in the beta cells of islets of
  langerhans in the pancreas.
• Insulin release cause increase movement of
  glucose into the cells and increase glucose
  metabolism
• Is the only hormone that decreases glucose levels
  and is referred as a hypoglycemic agent.

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Glucagon

• Peptide hormone that is synthesized by the alpha
  cells of the islets cells of the pancreas
• Released during stress and fasting states.
• Released in response to decreased body glucose.
• Main function is to
• increase hepatic glycogenolysis,
• and increase gluconeogenesis.
• Hyperglycemic agent

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Action of Hormones
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Epinephrine (adrenaline)

• Hormone produced by the adrenal gland
• Increases plasma glucose by
• inhibiting insulin secretion,
• increasing glycogenolysis
• and promotes lipolysis.
• Release during times of stress

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Glucocorticoids

• Primarily Cortisol is released when stimulated by
  adrenocorticotropic hormone (ACTH).
• Cortisol increases plasma glucose by
• increasing gluconeogenesis,
• Inhibition of glucose uptake in muscle
• and adipose tissue
• and lipolysis.
• Insulin antagonist

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Thyroxine

• The thyroid gland releases thyroxine.
• Increases glucose levels by
• increasing glycogenolysis,
• gluconeogenesis
• And intestinal absorption of glucose.

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Somatostatin

• Produced by the delta cells of the lslets of
  langerhans of the pancreas.
• The inhibition of insulin, glycagon
• Therefore only minor overall effect

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Hyperglycemia

• Increase in plasma glucose levels
• In healthy persons during a hyperglycemia state,
  insulin is secreted by the beta cells of the
  pancreatic islets of langerhans.
• Insulin enhances membrane permeability to cells
  in the liver, muscle, and adipose tissue.
• Hyperglycemia is caused by an imbalance of
  hormones.

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Diabetes Mellitus

• Metabolic diseases characterized by hyperglycemia
  resulting from defect in insulin secretion,
  insulin action or both.
• Two major types (in 1979)
• Type I, (insulin dependent) and Type 2, (non
  insulin dependent)
• 1995 further categories by WHO
• Type 1 diabetes, type 2 diabetes, other specific
  types and gestational diabetes mellitus.

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Type 1 diabetes

• Due to cellular-mediated autoimmune destruction
  of the ß cells of the pancreas, causing an
  absolute deficiency of insulin secretion
• Or idiopathic type 1 diabetes that has no known
  etiology
• Commonly occurs in children (juvenile diabetes)
• Constitutes only 10 to 20 of all cases of
  diabetes
• Genetics play a minimal role, can be due to
  exposure to environmental substances or viruses.
• Treatment insulin

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Characteristics of T1DM

• Abrupt onset,
• insulin dependence,
• and ketosis tendency.
• One or more of the following markers are found in
  85 to 90 of individuals with fasting
  hyperglycemia
• islet cell autoantibodies,
• insulin autoantibodies,
• glutamic acid decarboxylase autoantibodies

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Type 2 diabetes mellitus

• Due to insulin resistance and relative insulin
  deficiency .
• Type 2 constitutes the majority of the diabetes
  cases
• Most patients in this type are obese or have an
  increased percentage of body fat distribution in
  the abdominal region
• often goes undiagnosed for many years and is
  associated with a strong genetic predisposition

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Characteristics of T2DM

• Adult onset of the disease
• Ketoacidosis seldom occurring.
• These patients are more likely to go into a
  hyperosmolar coma
• and are at an increased risk of developing
  macrovascular and microvascular complications.

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Other specific types

• Secondary conditions,
• genetic defect in beta cell function
• or insulin action,
• pancreatic disease,
• disease of endocrine origin,
• drug or chemical induced.
• Characteristics of the disease depends on the
  primary disorder.

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Gestational diabetes mellitus

• Glucose intolerance that is induced by pregnancy
• Caused by metabolic and hormonal changes related
  to the pregnancy.
• Glucose tolerance usually returns to normal after
  delivery.
• An increased risk for development of diabetes in
  later years