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Carbohydrates
Carbohydrates
 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.
 Major sources of energy for the body.
 4 classifications: based on the number of
sugar units in the chain
 Monosaccharide
 Disaccharide
 Polysaccharide
 oligosaccharide
Monosaccharide
 CHO derivative formed by the addition of
chemical group: phosphate, sulfate, and amines.
 Example: glyceraldehydes (3 carbon compoundsmallest 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 Lglucose.)
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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, Dfructose, etc.
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 galactose)
and maltose (malt product) and are both
reducing agents.
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 waterhydrolysis.
 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.
 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)
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.
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.
 Maltase is an enzyme released by
intestinal mucosa.
 Sucrase and lactase: enzymes that
hydrolyze sucrose to glucose; fructose and
lactose to glucose and galactose.
 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 acidcausing the stomach upset and
discomfort.
 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.
 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.
 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:
 Glycolysis (Embden-Meyerhof )
 Hexose Monophosphate Shunt or (PPP)
 Glycogenesis (storage of glucose as
glycogen)
Embden-Meyerhof (EM)
 Glucose is broken down into two- 3 carbon
molecules of pyruvic acid. This enters TCAcycle 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.
EM continue
 Glycerol released from the hydrolysis of
triglyceride; which enters at 3phosphoglycerate.
 Beta- oxidation: where fatty acids, ketones
and some amino acids are catabolized to
acetyl CoA.
 Most amino acids enter as pyruvate.
Hexose Monophosphate Shunt
 2nd energy pathway
 Adetour for glucose -6-phosphate from glycolytic
pathway to convert and become 6phosphogluconic 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.
 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.
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 glycogenolysis.
 Long fasting states- glucose is
synthesized from tissue by glycogenolysis.
 Glycogensis: process if glycogen is
converted back to glucose-6-phosphate for
entry into glycolytic path.
 2 major hormones involved: Insulin and
glucagon; these hormones allow the body
to respond on as needed bases.
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.
 Hormones and endocrine systems work
together to meet 3 requirements:
 Steady supply of glucose.
 Store excess glucose
 Use stored glucose as needed
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.
Glucagon
 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
glycogenolysis, inhibit glycolysis and
increase gluconeogenesis.
 Hyperglycemic agent
Epinephrine
 Hormone produced by the adrenal gland
 Increases plasma glucose by inhibiting
insulin secretion, increasing
glycogenolysis and promotes lipolysis.
 Release during times of stress
Glucocorticoids
 Cortisol is released when stimulated by
ACTH.
 Cortisol increases plasma glucose by
decreasing intestinal entry into the cells
and increasing glycogenesis, liver
glycogen and lipolysis.
 Released during extended increase of
glucose
 Insulin antagonist
Thyroxine
 The thyroid gland is stimulated by
TSH to release thyroxin.
 Increases glucose levels by
increasing glycogenolysis. and
intestinal absorption of glucose.
Somatostatin
 Produced by the delta cells of the
lslets of langerhans of the pancreas.
 Increases plasma glucose levels by
the inhibition of insulin, growth
hormone and other endocrine
hormones.
Hyperglycemia
 Increased in plasma glucose levels.
 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.
 Due to hormone imbalance
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.
 1995: further categories by WHO/ADA:
Type 1 diabetes, type 2 diabetes, other
specific types and gestation diabetes
mellitus.
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 glucose levels
 Treatment: give insulin
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.
 Relative insulin deficiency
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.
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, and
hyperbilirubinuria.
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.
 Type 1: tend to produce ketones because
of the difference in glucagon and insulin
concentration through increased betaoxidation. Absence of insulin and with
increased glucagon which leads to
gluconeogenesis and lipolysis.
 Type 2: have very little ketone
production.
Lab findings Type 1
 Ketoacidosis that tend to reflect
dehydration, electrolyte imbalance,
acidosis's and oxidation fatty acids
producing acetoacetate, Betahydroxybutyrate and acetone. Betahydroxybutyrate 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.
Lab findings with Type 2
 Over production of glucose: > 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, in addition to N to elevated
sodium and potassium, slight decrease in
bicarbonate and increase in BUN:Creat ratio.
Hypoglycemia
 Decreased glucose levels
 Most effective on the CNS- why there is
shaking and tremors, heart rate increasesdizziness, cold sweat, if not corrected can
result in slurred speech, loss of motor
skills-unconsciousness-coma-death.
Glucose measurements
 Use serum, plasma or whole blood
 Sample needs to refrigerated and
separated from cells with one hour of
collection.
 Fluoride is the anticoagulant of choice.
 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 tartratewhich detects the reducing substance.
Methods
 Glucose oxidase method: converts beta-dglucose to gluconic acid. Mutarotase may be
added to facilitate to conversion to alpha-dglucose to beta-D-glucose. Oxygen is
consumed and hydrogen peroxide is produced.
Can measure the amount of oxygen loss or
H2O2 produced. Horseradish peroxidase is
used as a catalyst. Chromogens used for color
change: 3-methyl-2-benzothiazolinone
hydrozone and N,N – dimethylaniline- this is a
coupled reaction known as Trinder’s reaction
 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 dehydrogenaseproduces a red color measured at 340 nm.
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.
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
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)
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
Microalbuminuria
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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.)
24 hour (timed)
4 hour over night