Carbohydrates

MLTD 2107 Clinical Chemistry II: Carbohydrates

Overview of Carbohydrates and Energy

  • Energy Source

    • Oxidation of organic compounds (Carbohydrates, proteins, lipids) provides energy.

    • Carbohydrates (CHO’s) serve as the primary energy source for humans.

    • They are the main food source for the brain, red blood cells (RBC’s), and retinal cells.

    • Stored as glycogen in the liver and muscle but cannot be stored in nervous tissue.

  • General Composition

    • Composed of Carbon (C), Hydrogen (H), and Oxygen (O).

    • General formula: Cx(H2O)y, e.g., glucose represented as C6H{12}O6.

    • All carbohydrates contain carbonyl (C=O) and hydroxyl (–OH) functional groups.

    • Derivatives of carbohydrates can form through addition of other functional groups, such as phosphates or amines.

Classification of Carbohydrates

  1. Size of Base Carbon Chain

    • Classified based on the number of carbon atoms:

    • Triose (3 carbons), Hexose (6 carbons).

    • Smallest carbohydrate is Glyceraldehyde.

  2. Stereochemistry

    • Refers to the 3-dimensional arrangement of atoms around central asymmetric carbon atoms (each having four different groups attached).

    • Stereoisomers: compounds with the same types and order of bonds but different spatial arrangements.

    • Configuration types: “D” or “L” designated at the highest numbered asymmetric carbon; most human sugars are in D-form.

  3. Location of CO Functional Group

    • Aldose: carbonyl group located at the terminal carbon (aldehyde group), e.g., glucose.

    • Ketose: carbonyl group located in the middle (ketone group), e.g., fructose.

  4. Number of Sugar Units

    • Monosaccharides: 3-6 carbon atoms that cannot be hydrolyzed further, e.g., glucose, fructose, galactose.

    • Disaccharides: formed from joining two monosaccharides, producing water (e.g., maltose, lactose, sucrose).

    • Oligosaccharides: 2-10 sugar units.

    • Polysaccharides: more than 10 monosaccharide units, e.g., starch (digested by amylase), glycogen.

Reducing Substances

  • Carbohydrates must contain a free/active ketone or aldehyde group to be classified as reducing substances—they can reduce other compounds, resulting in the oxidation of the aldehyde or ketone group.

  • Reducing Sugars: all monosaccharides and many disaccharides (e.g., glucose, maltose, fructose, lactose, galactose).

  • Non-reducing Sugar Example: sucrose.

Glucose

  • Chemical Formula: C6H{12}O_6

  • Molecular Weight (MW): 180 grams

  • Sources of Glucose:

    • Derived from breakdown of carbohydrates in the diet, body stores (glycogen), and endogenous synthesis from proteins/lipids.

Glucose Metabolism

  • The nervous system relies entirely on a steady supply of glucose from extracellular fluid (ECF) and cannot store it.

  • If plasma glucose levels drop too low, there is a loss of nervous function.

  • Most ingested carbohydrates are polysaccharides that must be converted into disaccharides (by salivary and pancreatic amylase, e.g., maltose) for absorption.

Carbohydrate Digestion and Absorption

  • The intestinal mucosa processes various enzymes:

    • Maltase: converts maltose into glucose.

    • Sucrase: converts sucrose into glucose and fructose.

    • Lactase: converts lactose into glucose and galactose.

  • Monosaccharides are absorbed by the gut into the hepatic portal venous supply entering the liver.

    • Glucose (β-D-glucose): only carbohydrate used directly for energy or stored as glycogen.

    • Galactose and Fructose: converted into glucose by liver enzymes.

Metabolic Pathways for Glucose

  • Purpose of metabolism: convert glucose to CO₂ and H₂O while producing ATP.

  1. Initial Step: Conversion of glucose to glucose-6-phosphate (G6P) using ATP and hexokinase.

  2. Subsequent Pathways: G6P can enter three main pathways:

    • Embden-Meyerhof Pathway: main pathway for glucose oxidation; an aerobic process resulting in pyruvate and ATP production in cytosol.

    • Hexose Monophosphate Shunt (HMP): involved in NADPH production.

    • Glycogenesis: storage of glucose as glycogen.

Embden-Meyerhof Pathway

  • Aerobic reaction: Glycolysis yields pyruvate and 2 ATP.

    • Pyruvate enters mitochondria to become acetyl CoA, eventually entering the TCA cycle, producing an additional 2 ATP, NADH, FADH₂, CO₂, and H₂O.

    • Oxidative Phosphorylation: generates 34 ATP, CO₂, and H₂O.

  • Anaerobic reaction: In the absence of oxygen, pyruvate forms lactate.

    • Takes place in the cytosol, especially in muscles, yielding 2 moles of ATP and contributing to lactate recycling in the liver.

Key Terms in Glucose Metabolism

  • Gluconeogenesis: generation of glucose from non-carbohydrate sources (e.g., amino acids, glycerol).

  • Glycolysis: metabolism of glucose to pyruvate or lactate for energy production.

  • Lipogenesis: conversion of carbohydrates into fatty acids.

  • Lipolysis: breakdown of fatty acids for oxidation.

  • Glycogenolysis: breakdown of glycogen into glucose for use in energy production.

  • Regulatory Mechanisms:

    • The liver uses gluconeogenesis, lipolysis, and glycogenolysis to maintain blood glucose levels during fasting or low carbohydrate intake.

Hormonal Regulation of Blood Glucose Levels

  • Insulin

    • Produced by β cells of the islets of Langerhans; released when plasma glucose levels increase.

    • Functions as a hypoglycemic agent by enhancing the uptake of glucose into tissues (e.g., liver, muscle, adipose tissue) and promoting glycogenesis.

    • Inhibits glycogenolysis.

  • Glucagon

    • Produced by α cells of islets; acts as a hyperglycemic agent, elevating plasma glucose via glycogenolysis or gluconeogenesis.

  • Other Hormones Increasing Plasma Glucose

    • Epinephrine (Adrenaline): released during stress; inhibits insulin secretion, promotes glycogenolysis

    • Cortisol: released in response to ACTH or stress, promoting gluconeogenesis and hyperglycemia.

    • Growth Hormone (GH): decreases glucose uptake in cells, increases lipolysis, and gluconeogenesis.

    • Thyroid Hormones: stimulate gluconeogenesis and intestinal absorption of glucose.

Glucose Reference Intervals

  • Blood Glucose Levels:

    • Fasting: 3.9-5.5 mmol/L

    • Random: 3.9-11.0 mmol/L

    • Critical Values: ≤ 2.5 mmol/L or ≥ 25.0 mmol/L

  • Urine: 24-hour urine should be less than 2.8 mmol/day; renal threshold between 8.9-10.0 mmol/L.

Hyperglycemia and Diabetes Mellitus

  • Hyperglycemia represents a defect in insulin secretion and/or action, leading to diabetes mellitus (DM).

  • Types of Diabetes:

    • Type 1: Autoimmune destruction of β cells, leading to absolute insulin deficiency (10-20% of cases).

    • Type 2: Insulin resistance with defect in insulin secretion (majority of cases); may not require insulin therapy.

  • Clinical Signs of Type 1 Diabetes:

    • Abrupt onset, dependence on insulin, ketosis tendency, characterized by symptoms such as polyuria, polydipsia, polyphagia, rapid weight loss, fatigue, and others.

Laboratory Findings and Complications

  • For Type 1 Diabetes:

    • Hyperglycemia and Glucosuria when blood glucose exceeds 10.0 mmol/L.

    • Ketoacidosis: increased ketones, dehydration, high anion gap acidosis.

    • Complications from long-term diabetes include microvascular problems (nephropathy, neuropathy, retinopathy) and macrovascular diseases (cardiovascular diseases).

Type 2 Diabetes Insights

  • Clinical Characteristics:

    • Usually adult onset with milder symptoms than Type 1. Affected often by obesity, with the presence of insulin resistance.

    • Lab Findings: Primarily exhibit hyperglycemia, dyslipidemia, and often require various management strategies to prevent severe complications such as diabetic hyperosmolar nonketotic syndrome (HHS).

Testing and Diagnosis of Diabetes

  • Diagnosis Options:

    • Fasting plasma glucose ≥ 7.0 mmol/L, 2-hour OGTT with a post-load of 75 g ≥ 11.1 mmol/L, HbA1C ≥ 6.5 ext{%} , or symptomatic + random glucose ≥ 11.1 mmol/L.

  • Prediabetes and gestational diabetes management starts with routine screening and monitoring,

Other Conditions Related to Diabetes

  • Acute Complications: Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) which require immediate medical intervention.

  • Reference to genetic defects affecting glucose metabolism, such as glycogen storage diseases (e.g., von Gierke disease) and galactosemia, with diagnostics and treatment strategies outlined.

Laboratory Testing Purposes

  • Vital for diagnosing various carbohydrate disorders, monitoring glycemic control, screening for complications, and managing treatment strategies.

Glucose Measurement Methods

  • Methods: Enzymatic methods using glucose oxidase or hexokinase are standard. Understanding sources of error and maintaining accuracy in different sample types is critical for laboratory testing.

Conclusion and References

  • These notes synthesize essential information on the clinical chemistry involving carbohydrates, their metabolism, and related disorders prevalent within health contexts. Further reading, including reference textbooks and guidelines, is encouraged for comprehensive understanding.