Human biochem lecture 7

Chapter 9 – Carbohydrates

• Glycogen, GSDs, and other CHO molecules

• Lecture Date: January 28th, 2025

• Reading Material: Biochemistry: Concepts and Connections, Chapter 9 (Pages 279-303)

Lecture Overview

• Relevant Disease Topic: Glycogen and Glycogen Storage Diseases (GSDs)

• Key Topics Covered:

  • Monosaccharides

  • Types and shapes of monosaccharides

  • Oligosaccharides

  • Polysaccharides and their structures

  • Hybrid structures from monosaccharides

  • Glycoproteins and blood types

• More detailed talk on metabolism to be covered in future lectures (Chapters 11 and beyond)

• Test Information: Tests should return by next week (Tuesday)

Glycogen Storage Diseases

• Definition of Glycogen:

  • Storage molecule composed of glucose units, tightly bound for quick availability

  • Similarity to plant storage molecules such as amylopectin

Pathway of Glucose Metabolism

• Glucose can be:A. Used in glycolysis and the Kreb’s cycleB. Stored as glycogen

• Enzyme activity levels crucial for metabolic function; deficiencies may lead to GSDs

Glycogen Storage Diseases – Overview

• Numerous defects possible in glycogen metabolism

• Highlighted congenital defects include:

  • Type I (von Gierke Disease): Glucose-6-phosphatase deficiency

  • Type II (Pompe Disease): Acid maltase deficiency

  • Type III (Cori or Forbes Disease): Debranching enzyme deficiency

  • Type IV (Andersen Disease): Branching enzyme deficiency

  • Type V (McArdle Disease): Muscle glycogen phosphorylase deficiency

  • Type VI (Hers Disease): Liver glycogen phosphorylase deficiency

  • Type VII (Tarui Disease): Muscle phosphofructokinase deficiency

  • Type IX: Liver phosphorylase kinase deficiency

Glycogen Storage Disease Type 1

• Common Name: von Gierke’s disease

• Genetics: Autosomal recessive, requires deficient enzyme copies from both parents

• Key Cause: Deficiency in glucose-6-phosphatase enzyme

Pathology of Glycogen Storage Disease Type 1

• Affects organs involved in glycogen storage: mainly the liver, also kidneys and intestines

• Main Clinical Findings:

  • Hepatomegaly (enlargement of the liver)

  • Hypoglycemia (insufficient glucose in blood)

• Other GSDs present different pathologies based on specific enzyme deficiencies

Treatment of Glycogen Storage Diseases

• Treatment varies by disease type

• Specific Treatment for GSD1a:

  • Diet including uncooked corn starch to provide a stable glucose source

• Metabolic interventions can help prevent severe complications

Monosaccharides

• Definition: Simplest carbohydrate molecules, composed of one structural unit

• Smallest carbohydrate units are trioses (three-carbon compounds)

• Carbon arrangements differ among monosaccharides

Aldoses and Ketoses

• Definitions:

  • Aldoses: Contain a double-bonded oxygen at the end of the carbon chain

  • Ketoses: Contain a double-bonded oxygen in the middle of the chain

Enantiomers

• Mirror images of same molecular composition

• D-enantiomers are commonly used in metabolism due to enzyme specificity

Monosaccharides with 4+ Carbons

• Types of Monosaccharides:

  • Tetroses (4 Carbons)

  • Pentoses (5 Carbons)

  • Hexoses (6 Carbons)

• Increasing carbon number increases diastereomers

Ring Structures of Monosaccharides

• Pentoses and hexoses can form ring structures

• Types of ring structures:

  • Pyranoses: Six-membered rings (with oxygen)

  • Furanoses: Five-membered rings

Carbohydrate Isomers

• Types of Isomers:

  • Enantiomers: Mirror images

  • Diastereomers: Non-mirror images

  • Anomers: Differ in the position of the OH group at the anomeric carbon

  • Epimers: Differ at one non-anomeric carbon

  • Conformational isomers: Same configuration, different shapes

Oligosaccharides

• Simplistically defined as all carbohydrates consisting of more than one monosaccharide

• Examples: Disaccharides like sucrose and maltose

• Structural characteristics for distinction:

  1. Monomer types and configurations

  2. Carbon linkages

  3. Connection order between monomers

  4. Configuration of the anomeric OH group

Polysaccharides

• Functions: Storage (amylose, amylopectin, glycogen) and structure

• Only slight structural differences in storage polysaccharides:

  • Amylose: Linear, alpha-linked 1-4 glucose molecules

  • Glycogen and amylopectin: Branching at 1-6 carbon atoms

Structural Polysaccharides

• Cellulose:

  • Composed of beta 1-4 linked glucose units

  • Strong structures due to hydrogen bonding and difficult-to-dismantle linkages

• Chitin:

  • Similar to cellulose but with acetylated amino groups, forming invertebrate exoskeletons

Glycoproteins

• Proteins with oligosaccharides or polysaccharides attached

• Functions include roles in hormones (e.g., erythropoietin) and protective mucins

N- and O-linked Glycoproteins

• N-linked: Attached to amide group (e.g., asparagine)

• O-linked: Attached to hydroxyl group (threonine, serine, etc.)

Blood Group Antigens

• Related to O-linked glycoproteins (glycolipids)

• Improper transfusions can cause blood cell agglutination

• Importance of knowing blood types in transfusions

Next Class

• Test 1: Covering all materials from previous lectures (1-6)

• Reminder for test preparation.