Carbs (CC1 Lec)

Carbohydrates

Carbohydrates

Organic compounds that serve as the primary energy source and are composed of carbon, hydrogen, and oxygen.

Classification of Carbohydrates

1. Size of the mase carbon chain

2. location of the carbonyl functional group.

3. based on the stereochemistry of the compound.

4. number of sugar unit.

L type (levorotatory type)

A type of carbohydrate that rotates light in a counter clockwise direction.

D type (Dextrorotatory type)

A type of carbohydrate that rotates light in a clockwise direction.

Monosaccharides

The simplest form of sugar that cannot be further hydrolyzed.

Sucrose

most common non-reducing sugar. Do not contain ketone and aldehyde group.

Dissacharide

Formed by interaction of two monosaccharides; connected by a bond (glycosidic bond)

Maltose

Glucose + Glocuse

Lactose

Glucose + Galactose

Sucrose

Glucose + fructose

Polysaccharides

Carbohydrates composed of more than 10 monosaccharide units.

Starch

most common polysaccharide in the diet. Exogenous.

Glycogen

formed in the body from glucose and stored in the muscle and liver.

Cellulose

polysaccharide found in plants; not digested in the digestive system of the individual; excreted in the undigested form

Fisher/ Fischer Projection

straight linear chain and show representation of the cyclic form.

Haworth projection

most representative of the actual CHO structure.

Glycolysis

“EMP Pathway”

Metabolism of glucose to lactate or pyruvate for production of energy

Lactate is generated with ATP in anaerobic

Pyruvate is generated with ATP in aerobic

Gluconeogenesis

Formation of glucose-6-phosphate from non-carbohydrate source.

Glycogenesis

Conversion of glucose to glycogen for storage in liver and muscles.

Glycogenolysis

Breakdown of glycogen to glucose-6- phosphate.

Lipogenesis

Conversion of CHO to fatty acids

Lypolysis

Decomposition of fat

Insulin

A hormone responsible for decreasing blood glucose levels.

Insulin function

Promotes cell uptake of glucose and promote glycolysis

Promotes glycogenesis of excess glucose (converted into liver and muscles)

Promotes lipogenesis (excess glucose is converted into fatty acids and triglycerides that are stored in the adipose tissue)

Glucagon

Primary hormone responsible for increasing blood glucose.

Synthesized by the alpha cells of the islets of Langerhans in the pancreas. Regulates blood glucose by increasing glycogenolysis and gluconeogenesis.

Epinephrine

Produced by the adrenal cortex in response to ACTH, increases plasma glucose. Decreases intestinal entry of glucose into the cell and increases gluconeogenesis, glycogenolysis, and lipolysis. Associated with stress and promotes the inhibition and secretion of insulin and promotes glycogenolysis and lipolysis.

Cortisol (Glucocorticoids)

Produced by the adrenal cortex in response to ACTH, increases plasma glucose. Lowers interstitial entry of glucose into the cell and promotes gluconeogenesis, glycogenolysis, and lipolysis.

Growth hormone

Produced by the anterior pituitary gland, increases plasma glucose. Decreases glucose entry to cells and increases glycolysis.

Thyroxine (T4)

Produced by the thyroid gland, increases plasma glucose. Promotes glycogenolysis, gluconeogenesis, and glucose intestinal absorption.

Somatostatin

Produced by the Delta cells of the islets of Langerhans in the pancreas and hypothalamus. Affects glucagon and growth hormone. Increases plasma glucose by inhibiting insulin, glucagon, and growth hormone.

Causes of Hyperglycemia

• Stress

• Severe infection

• Dehydration

• Pregnancy

• Pancreatectomy

• Hemochromatosis

• Insulin deficiency or abnormal insulin receptor

Hyperglycemic FBS levels

≥126 mg/dL

Normal FBS level

70-110 mg/dL

Impaired fasting glucose/borderline fasting glucose

111-125 mg/dL

Diabetes Mellitus

Metabolic disease (all about hormone abnormality) characterized by hyperglycemia resulting from defects in insulin secretion, insulin or both.

Type 3 DM

• proposed type or still a candidate; classification between type 1 and type 2

• DM that is linked or associated with the development of Alzheimer’s disease.

DIAGNOSTIC CRITERIA FOR DIABETES MELLITUS

1. Random plasma glucose ≥200mg/dL, + symptoms of diabetes

2. Fasting plasma glucose that is equal or greater than 126 mg/dL

3. 2-h plasma glucose ≥200 mg/dL during an OGTT

Normal glucose tolerance

2-h PG <140 mg/dL

Impaired glucose tolerance

2-h PG 14-199 mg/dL

Provisional diabetes diagnosis

2-h PG ≥200 mg/dL

OGT Load

Non pregnant female and male: 75g glucose load

Kids: 1.75g glucose load per kg body weight

Pregnant: 100g glucose load

Diagnostic criteria for gestational diabetes mellitus

1. 1-h plasma glucose ≥140 mg/dL during an OGTT + symptoms of gestational diabetes (100 grams glucose load)

2. 3-h plasma glucose: Fasting (8-14 hrs) – >95 mg/dL; 1 hr – ≥180 mg/dL; 2 hrs – ≥155 mg/dL; 3 hrs – ≥140 mgdL)

Hypoglycemia

Low/decreased plasma glucose level, imbalance between glucose utilization and production

Important plasma level values

65-70 mg/dL - glucagon and other hyperglycemic agents are already released

50-55 mg/dL – there are already observable signs and symptoms of hypoglycemia; majority are related to CNS.

Neurogenetic symptoms of hypoglycemia

Tremors, palpitations, anxiety, and diaphoresis (excessive perspiration)

Neuroglycopenic symptoms of hypoglycemia

Dizziness, tingling sensation, blurred vision, confusion, behavioral changes

laboratory Findings of Hypoglycemia

• Decrease glucose in plasma.

• Increased in patients with pancreatic βcells tumors (insulinoma) – insulin levels are high; tumors promote over secretion of insulin

Galactosemia

Congenital deficiency of one of three enzymes involved in galactose metabolism

Galactose-1-phosphate uridyl transferase

Most common enzyme deficient in galactosemia.

Essential fructosuria

Autosomal recessive disorder characterized by fructokinase deficiency

Hereditary fructose deficiency

Defect of fructose 1-6-biphosphate aldolase B activity in the liver, kidney, and intestine

Fructose 1-6-biphosphate deficiency

Defect in fructose-1-6 biphosphate resulting in failure of hepatic glucose generation

Von Gierke disease

Most common glycogen storage disease; type 1A; liver and muscle are affected

CSF glucose

About 40-60% of the blood plasma glucose level.

• Increased levels: diabetes

• Decreased levels: bacterial meningitis, tuberculosis, fungal and amebic meningitis, subarachnoid hemorrhage, systemic hypoglycemia.

• Viral meningitis: CSF Glucose is unaffected because viruses do not utilize glucose. It needs a living hose

Reference values of CSF Glucose

40-70 mg/dL (adult)

60-80 mg/dL (child)

Normal CSF-to-Glucose ratio

<0.5

C-peptide test

A test that measures the level of C-peptide in the blood, which provides an indicator of pancreatic and insulin secretion.

Nelson Somogyi method

A copper reduction method used BaSO4 to remove saccharoids

Glucose + arsenomolybdic acid → arsenomolybdenum blue

Utilizes direct colorimetric method (measured colorimetically); increased absorbance.

Hagedorn Jensen method

A ferric reduction method (inverse colorimetry)

Glucose + Ferricyanide (yellow) → Ferrocyanide (colorless)

• Color reactant is reduced to colorless; decreased absorbance

Ortho-toluidine method

A method that utilizes condensation of carbohydrates with aromatic amines to produce Schiff bases (Green).

Utilizes direct colorimetric method (measured colorimertically); increased absorbance.

Glucose oxidase method

An enzymatic method that measures glucose levels by oxidizing glucose and measuring the resulting reaction.

• B-D-glucose + H2O – glucose oxidase → gluconic acid + H2O2

• H2O2 + reduce chromogen- peroxidase → oxidized chromogen + H2O

• Couple reaction is known Trinder’s reaction

Hexokinase method

A reference method for measuring glucose levels that involves the conversion of glucose to glucose 6-phosphate.

• Glucose + ATP -hexokinase → glucose 6-PO4 + ADP

• Glucose 6-PO4 + NADP+ ―G-6-PD → NADPH + H+ 6-phosphogluconate

• ↑ in absorbance is measured at 340 nm

Clinitest

A test that detects reducing substances, including glucose, by reacting with copper ions.

Reducing substance + Cu+2 → Cu+1 O

Self monitoring of Blood glucose

Type 1 Diabetes (3-4 times/day)

Oral glucose tolerance test

• A solution containing 75g (adults) or 1.75g/kg (children) of glucose is administered, and a 2-Hour Postprandial Tests specimen is drawn 2 hrs later.

• The patient’s glucose is determined in 30 min, 1st, 2nd, and 3rd hr.

HbA1C

Hemoglobin A1C, an index for long-term plasma glucose control that indicates compliance and efficacy of diabetes mellitus therapy.

Values of HBA1C

Normal value: 4.5 to 8.0%

o Normal: px complies/ medication is effective (for px diagnosed with diabetes).

o High hba1c: px do not follow/medication is not effective.

METHODS OF HBA1C MEASUREMENT BEASED ON STRUCTURAL DIFFERENCES

• IMMUNOASSAYS

• AFFINITY

• CATION-EXCHANGE CHROMATOGRAPHY

• ELECTROPHORESIS

• ISOELECTRIC FOCUSING

• HPLC

IMMUNOASSAYS

Polyclonal or monoclonal antibodies toward the glycated Nterminal group of the B chain of Hb

AFFINITY

Separated based on chemical structure using boronate group

to bind glycosylated proteins.

CATION-EXCHANGE CHROMATOGRAPHY

Positive-charge resin bed attaches to negatively charged hemoglobin.

ELECTROPHORESIS

Separation is based on differences in charge.

ISOELECTRIC FOCUSING

Type of electrophoresis using isoelectric point to separate.

HPLC

A form of ion-exchange chromatography Separates all forms of HbA1C (A1a, A2b, A2c)

3 Ketone bodies

Acetone (2%)

Acetoacetic acid (20%) – most commonly tested

3-B-hydroxybutyric acid (78%)

Ketonemia

Accumulation of ketones in the blood.

Ketonuria

Accumulation of ketones in the urine.

Gerhardt's Test

A test that detects acetoacetic acid by reacting with ferric chloride to produce a red color.

Nitroprusside Test

A test that detects acetoacetic acid by reacting with nitroprusside to produce a purple color.

–alkaline pH→ Purple color

Enzymatic method

A method that measures ketones by using enzymes to convert them to other compounds and measuring the resulting reaction.

NADH + H+ + acetoacetic acid –β-HBD→ NAD + βhydroxybutyric acid

Microalbuminuria

The presence of small amounts of albumin (a protein) in the urine, indicating early-stage diabetic renal nephropathy.

Persistent albuminuria in the range of 30-299 mg/24 hr or albumin creatinine ratio of 30 to 300 µg/mg.