Chapter 11 Carbohydrates

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Chapter 11Carbohydrates
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Carbohydrates CHO

• Compounds containing C, H, O
• 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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• Major sources of energy for the body.
• 4 classifications based on the number of sugar
  units in the chain
• Monosaccharide
• Disaccharide
• Polysaccharide
• oligosaccharide

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Monosaccharide

• CHO derivative formed by the addition of chemical
  group phosphate, sulfate, and amines.
• Example glyceraldehydes (3 carbon compound-
  smallest CHO)
• CHO is aldehyde called aldose
• CHO is ketone called ketose
• D- and L- form used to describe possible isomers
  of glucose. Ex ( D-glucose and L-glucose.)

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• CHO forms depend on
• Fisher projections
• Hawarth Projections
• Most CHO are of the D- forms and are
  monosaccharide such as D-glucose, D-fructose,
  etc.

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Disaccharides

• Formed from two monosaccharide with the
  production water.
• Most common form is sucrose (table sugar), which
  is glucose and fructose and is a non reducing
  sugar. Other forms include Lactose (glucose and
  galatose) and maltose (malt product) and are
  both reducing agents.

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Polysaccharides

• Starch- plants (cellulose) not digested by
  humans.
• Glycogen stored form of CHO in the liver.
• Formed by the combination of monosaccharide.
• Two CHO molecules join to generate water.
• Two CHO molecules spilt to loose water-
  hydrolysis.

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• Starch principle CHO (polysaccharide) storage
  product of plants
• Glycogen principle CHO storage product in
  animal.
• Glycoside linkage of CHO involves many CHO- some
  carbons favor linking depending on the CHO.
• All monosaccharide and many disaccharides are
  reducing agents because they contain a free
  aldehyde or ketone that can be oxidized.

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• Example of reducing agents is maltose and lactose
  are reducing agents because they contain a free
  aldehyde or ketone that can be oxidized.
• Starch and glycogen storage products, range in
  different sizes, similar because of their main
  chain composed of 1,4 glycoside linkage.
• Glycogen is more branched than starch and is
  shorter (branching permits more larger amount of
  CHO in small volume)

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Glucose Metabolism

• Glucose is a primary source of energy.
• Various tissues and muscles throughout the body
  including ECF depend on glucose for energy.
• 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 as starch and glycogen.
• Amylase digest the no absorbable forms of CHO to
  dextrin and disaccharide which are hydrolyzed to
  monosaccharide by maltose.
• Maltose is an enzyme released by intestinal
  mucosa.
• Sucrase and lactase enzymes that hydrolyze
  sucrose to glucose fructose and lactose to
  glucose and galatose.

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• Lactose intolerance due to a deficiency of
  lactase enzyme on or in the intestinal lumens,
  which is need 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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• Glucose metabolism disaccharides are converted
  into monosaccharide absorbed by the stomach
  transported to the liver by the hepatic portal
  venous blood supply.
• Glucose is the only CHO to be directly use for
  energy or stored as glycogen. Others have to be
  broken down then utilized for energy and storage.

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• After glucose is absorbed it can go into one of
  three metabolic pathways based on (1)
  availability of substrate and (2) nutritional
  status of cell.
• Ultimate goal to convert glucose to CO2 and H2O.
• Requires ATP and ADP, O2 in the final step.
• NADH acts as intermediate ATP is gained.

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

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Embden-Meyerhof (EM)

• Glucose is broken down into two- 3 carbon
  molecules of pyruvic acid. This enters TCA-cycle
  and oxidized to 2 molecules of lactic acid.
• Enters anaerobic glycolysis- no O2 required this
  important for body function and tissue function
  that required little or no oxygen supply for
  energy production.
• 2 molecules of ATP for each mole of glucose
• 4 molecules of ATP- net gain of 2 moles of ATP.

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EM continue

• Glycerol released from the hydrolysis of
  triglyceride which enters at 3-phosphoglycerate.
• Beta-knoop oxidation where fatty acids, ketones
  and some amino acids are catabolized to acetyl
  CoA.
• Most amino acids enter as pyruvate.

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Hexose Monophosphate Shunt

• 2nd energy pathway
• Adetour for glucose -6-phosphate from glycolytic
  pathway to convert and become 6-phosphogluconic
  acid.
• Formation of ribose-5-phosphate and nicotinamide
  dinucleotide phosphate.
• Allows pentose (ribose) to enter glycolytic
  pathway.
• If energy requirements met within the body the
  glucose goes to storage as glycogen.

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• 3rd pathway Final stage
• Conversion of glycerol, lactate, pyruvate to
  glucose- occurs by amino acid conversion by the
  liver and kidneys.
• Glucose-6-phosphate converted to
  glucose-1-phosphate to uridine diphosphoglucose
  then to glycogen.
• Liver and muscle synthesize glycogen.
• Within the liver, heptocyte release glucose to
  maintain blood glucose levels.
• Glucose-6-phophate is necessary, if glucose is
  absent it is not metabolize.

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Regulation of carbohydrate metabolism

• The liver, pancreas and endocrine gland keep
  blood glucose levels within a narrow range.
• During brief fasting states (between meals)
  glucose supplied to ECF from the liver through
  glycogenloysis.

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• Long fasting states- glucose is synthesized from
  tissue by glucogenesis.
• Glucogensis process if glycogen is converted
  back to glucose-6-phosphate for entry into
  glycolytic path.
• 2 major hormones involved Insulin and glucogen
  these hormones allow the body to respond on as
  needed bases.

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Hormone regulation

• Hormones effect the entry of glucose into cells
  and fate in the cells within the body.
• As needed hormones regulate release of glucose.
  (exp after meals glucose increase, without
  hormones to shut off secretion, the mechanism of
  glucose release would steadily increase.

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• Hormones and endocrine systems 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 in the cell.
• Synthesized in the beta cells of islets of
  langerhans in the pancreas.
• As the beta cells detect in increase in body
  glucose, they release insulin.
• 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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Glucogon

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

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Epinephrine

• 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

• Cortisol is released when stimulated by ACTH.
• Cortisol increases plasma glucose by decreasing
  intestinal entry into the cells and increasing
  glucogenesis, liver glycogen and lipolysis.
• Released during extended increase of glucose
• Insulin antagonist

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Thyroxine

• The thyroid gland is stimulated by TSH to release
  thyroxin.
• Increases glucose levels by increasing
  glycogenolysis, glucogenesis and intestinal
  absorption of glucose.

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Somatostatin

• Produced by the delta cells of the lslets of
  langerhans of the pancreas.
• Increases plasma glucose levels by the inhibition
  of insulin, glycagon, growth hormone and other
  endocrine hormones.

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Hyperglycemia

• Increased in plasma glucose levels.
• During a hyperglycemia state, insulin is secreted
  by the beta cells of the pancreatic islets of
  langerhan.
• Insulin enhances membrane permeability to cells
  in the liver, muscle, and adipose tissue.
• Due to hormone imbalance

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Diabetes Mellitus

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

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Type 1 diabetes

• Deficiency or loss of insulin production due to
  beta cell destruction.
• Commonly occurs in children (juvenile diabetes)
• Genetics play a minimal role, can be due to
  exposure to environmental substances or viruses.
• Clinical picture less than 20 yrs old, polyuria,
  weight loss, increased levels
• Treatment give insulin

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Type 2 diabetes mellitus

• Due to lack of or no insulin production, insulin
  resistant.
• Seen adults greater than 20 yrs old, most common
  adult form.
• Genetics play a larger role in addition to diet
  and genetics.
• Relative insulin deficiency

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Other specific types

• Secondary condition, 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.
• Infants are at a high risk for developing
  respiratory stress disorder, hypoglycemia and
  hyperbilirubinuria.

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Pathophysiology of Diabetes Mellitus

• Type 1 and Type 2 diabetes there is an increase
  in blood glucose levels (hyperglycemic). There
  is also elevation of glucose in urine
  (glucosuria) if glucose levels in blood exceed
  180 mg/dl.

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• Type 1 tend to produce ketones because of the
  difference in glucagon and insulin concentration
  through increased beta-oxidation. Absence of
  insulin and with increased glucagon which leads
  to gluconeogenesis and lipolysis.

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• Type 2 have very little ketone production, but
  have a greater tendency to develop hyperosmolar
  nonketonic states. There is increased insulin
  production and less use of glucagon.

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Lab findings Type 1

• Ketoacidosis that tend to reflect dehydration,
  electrolyte imbalance, acidosis's and oxidation
  fatty acids producing acetoacetate,
  Beta-hydroxybutyrate and acetone.
  Beta-hydroxybutyrate and acetone contribute to
  acidosis condition.
• Bicarbonate and total carbon dioxide are
  decreased due to deep respiration- body trying to
  compensate for acidosis by blowing off CO2 and
  removing H ions.

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• Anion gap greater than 16 mmol/L
• Serum osmoality is increased
• Sodium decreased due to polyuria and shift in
  water from cells.
• Hyperkalemia is almost always present due to
  displacement of potassium in cells that occurs in
  acidosis.

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Lab findings with Type 2

• Over production of glucose gt 300-500 mg/dl
• Dehydration due to the inability to excrete
  glucose in urine.
• No ketones bodies formed because of the lack of
  lipolysis.
• Can lead to coma if glucose levels reach gt 1000
  mg/dl, in addition to N to elevated sodium and
  potassium, slight decrease in bicarbonate and
  increase in BUNCreat ratio, increased osmolity.

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Hypoglycemia

• Decreased glucose levels
• Most effective on the CNS- why there is shaking
  and tremors, heart rate increases- dizziness,
  cold sweat, if not corrected can result in
  slurred speech, loss of motor skills-unconsciousne
  ss-coma-death.
• Causes Table 11-8
• Post absorptive hypoglycemia-fasting
  hypoglycemia-loss of glycemic control.

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Insulinoma

• Tumor that secretes insulin- no counter measure
  use for treatment.
• Extremely elevated insulin levels with decreased
  glucose levels.

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Genetic defects

• Glycogen storage defect is due to a defiance of
  specific enzyme that cause an alternation of
  glycogen metabolism.
• Most common form is glucose-6-phosphate
  deficiency type 1 von Gierke disease. Disease
  is characterized by hypoglycemia in addition to
  metabolic acidosis, ketonemia, and increased
  lactate and alanine levels.
• Hypoglycemic state is due to the inability of
  glycogen to be converted back to glucose by
  hepatic glycogenolysis.

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• Glycogen build up in the liver
• Patient exhibits hyperlipidemia, uricemia, and
  growth retardation.

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Galactosemia

• Failure to thrive syndrome in infants.
• Defect in enzyme needed to metabolize galatose-
  results in an increase in galatose in plasma.
• Enzyme that is most commonly deficient
  galatose-1phosphate uridyl transferase.
• Due to inhibition of glycogenolysis accompanied
  by diarrhea and vomiting.
• Must remove galactose from diet, if not will
  build up in the system cause retardation and
  cataracts.

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Glucose measurements

• Use serum, plasma or whole blood (WB is 15 less
  than serum or plasma)
• Sample needs to refrigerated and separated from
  cells with one hour of collection.
• Fluoride is the anticoagulant of choice.
• Glucose has the ability to function as a reducing
  agent and aid in the detection of and quatitation
  of carbohydrates .

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• Glucose and other carbohydrates are capable of
  converting cupric ions in an alkaline solution to
  form cuprous ions.
• Benedict and Fehlings reagent uses cuprous
  /cupric methodology forming a deep blue to red
  color when cuprous ions are present. Reagent
  contains alkaline solution of cupric ions
  stabilized by citrate or tart rate- which detects
  the reducing substance.

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• Uses the ability of the reducing agent to form
  Schift bases with aromatic amines.
• O-toludine (hot acid solution) wields a color
  compound _at_ 630nm when measuring carbohydrate but
  galatose and mannose react with O-toludine and
  can interfere with this reaction.

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Methods

• Glucose oxidase method converts beta-d- glucose
  to gluconic acid. Mutarotase may be added to
  facilitate to conversion to alpha-d-glucose to
  beta-D-glucose. Oxygen is consumed and hydrogen
  peroxide is produced. Can measure the amount of
  oxygen loss or H2O2 produced. Horseradish
  perixidase is used as a catalyst. Chromagens
  used for color change 3-methyl-2-benzothiazolinon
  e hydrozone and N,N dimethylaniline- this is a
  coupled reaction known as Trinders reaction

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• Hexokinase more accurate less interference from
  uric acid, bilirubin and ascorbic acid.
• In the presence of ATP- hexokinas converts
  glucose to glucose-6-phosphate.
• Glucose-6-phophate and NADP converted to
  6-phosphogluconate and NADPH by
  glucose-6-phosphate dehydrogenase- produces a red
  color measured at 340 nm.

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Glucose monitoring and 2 hr test

• 2 hour test utilizes the knowledge that normally
  a glucose level will return to normal after 2 hrs
  if no disease or impairment involved.
• GTT most sensitive, more accurate. Utilizes
  fasting along with set time intervals.

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Glycosylated Hemoglobulin (HbA1c)

• Is a term used to describe the formation of Hgb
  compound formed when glucose reacts with the
  amino group of Hgb.
• Used to monitor and manage diabetes, monitors
  blood glucose levels over the last 60-90 days.
• Specimen of choice is EDTA whole blood

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Methods

• 2 major categories
• Based on charge difference between glycosylated
  and nonglycosylated Hgb. (cation-exchange
  chromatography, electrophoresis, and isoelectric
  focusing)
• Structural characteristics of glycogroups on Hgb.
  (affinity chromatography and immunoassay)

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Ketones

• Ketone bodies are produced by the liver through
  the metabolism of fatty acids to provide energy
  to provide ready energy from stored lipids in low
  CHO available.
• Acetone (2), Beta-hydroxybutyrate (78 ) and
  acetoacetic acid (20).
• Low levels present all the time, but when the
  body is deprived if CHO (diet, vomiting, and
  glycogen storage disease) ketones levels
  increase.
• Ketonemia and ketonuria

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Microalbuminuria

• Because Diabetes mellitus cause progressive
  disease in the kidneys (nephropathy), the lab
  will monitor urinary albumin through measuring
  microalbumin in the urine.
• 3 methods
• Spot random urine test (albumin to creatinine
  ratio.)
• 2. 24 hour (timed)
• 3. 4 hour over night