Glycogenesis and Glycogen Metabolism

Housekeeping

Slides updated with corrections.
Science remains the same, wording and details adjusted.

Glyconeogenesis and Glycogen Metabolism

Lecture 3 of 8.

Carbohydrates

Simple: Monosaccharides and disaccharides.
Complex: Polysaccharides (many sugars linked).
Bread and pasta are ultimately broken down into sugars.
Complex carbs are better as they release sugar slower.
Chocolate (mono/disaccharides): rapid sugar flood.
Complex carbohydrates: slow, sustained release.
Number of carbons in a sugar (tri-, tetra-, pento-).
Aldehyde vs. ketone containing sugars.
Chirality: D-sugars preferred for sweetness.
Glycolysis: Glucose to pyruvic acid, net $2$ ATP produced.

Learning Objectives

List the four categories.

Pyruvic Acid Pathways

From glycolysis, pyruvate can follow anaerobic (no oxygen) or aerobic (oxygen) pathways.
Pathway depends on conditions.

Anaerobic Alcoholic Fermentation

Microbreweries: Using sugars (from starch in hops, wheat, potatoes) to make alcohol.
Equation:
$Sugars \rightarrow Pyruvic\;Acid + CO_2 \rightarrow Ethanol$ .
Any starchy plant material can be fermented into alcohol.

Anaerobic Lactic Acid Fermentation

Occurs in muscles during intense exercise.
Insufficient oxygen for aerobic oxidation.
Lactic acid or lactate is produced, causing muscle soreness.
Equation:
$Pyruvic\;Acid \rightarrow Lactic\;Acid/Lactate$ .
Usain Bolt sprints: Primarily anaerobic.

Aerobic Oxidation

Occurs under normal conditions.
Pyruvic acid is converted into carbon dioxide and water.
Equation:
$Pyruvic\;Acid + O2 \rightarrow CO2 + H_2O$

NADH vs. NADPH

NADH structure: Nicotinamide adenine dinucleotide with an extra hydrogen.
Difference: NADPH has an extra phosphate group.
NADPH: Used in anabolism (building up).
NADH: Used in catabolism (breaking down).

Acetyl Coenzyme A

Pyruvate + Coenzyme A $\rightarrow$ Acetyl Coenzyme A
Involves thiol group (-SH on coenzyme A).
Acetyl CoA enters the citric acid cycle.

Citric Acid Cycle (Krebs Cycle)

A rite of passage for biology students.
Pyruvate converts to Acetyl CoA.
Acetyl CoA, then cycles to make ATP, NADH, FADH2 and other byproducts.
NADH: Hydrogen transfer.
FADH2: Electron transport.

Gluconeogenesis

Brain requires constant glucose supply (20% of body's usage).
Body needs about 60g of glucose a day.
Keto diet (low-carb and sugar): Forces body to make glucose from fats.
Gluconeogenesis: Creating glucose from non-carbohydrate sources.
Reverse of glycolysis.
Occurs when glucose intake is insufficient.
Pyruvate/Lactate $\rightarrow$ Glucose

Precursors for Gluconeogenesis

Glycerol.
Lactate.
Pyruvate.
Propanoate.
Glucogenic amino acids (e.g., alanine).
All have three carbons.

Location

Primarily in the liver.
Fatty liver impairs gluconeogenesis, leading to type 2 diabetes.
Type 2 diabetes can cause hypoglycemia (low blood glucose).

Diabetic Coma

Can result from both hyperglycemia (high glucose) and hypoglycemia (low glucose).
First aid treatment: Give sugar (soft drink, not diet).
Sucrose/fructose in soft drinks is easily converted to glucose.
Gluconeogenesis costs the body energy.
Continuous process, regulated by body according to need.

Glycogen Synthesis

Excess sugar is stored as glycogen.
Occurs in muscles and liver.
Muscles for immediate energy needs.
Liver for glucose balance.
Glycogen formula: $(C6H{10}O5)n$ (polymer of glucose).
Animals store glucose as glycogen.

Glycosidic Bonds

Glycogen is a branched polysaccharide for compact storage.
1-4 glycosidic bonds (linear chain).
1-6 glycosidic bonds (branching).
Alpha configuration (OH group pointing away from $CH_2$ ).

Glycogen Synthesis Process

Glucose $\rightarrow$ Glucose-6-Phosphate (first step of glycolysis).
Glucose-6-Phosphate $\rightarrow$ Glucose-1-Phosphate.
UTP (Uridine Triphosphate) involved.
UTP $\rightarrow$ UDP-glucose + PPi (pyrophosphate).
UDP-glucose adds to glycogen chain.

Glycogen Breakdown (Glycogenolysis)

Occurs when sugar is needed.
Breaks 1-4 glycosidic bonds to release Glucose-1-Phosphate (G1P).
Uses different enzymes to break 1-6 glycosidic bonds.
G1P converted to Glucose-6-Phosphate (G6P).
G6P enters glycolysis or dephosphorylated to release glucose into bloodstream.

Regulation of Glycogen Metabolism

Glycogenesis (synthesis) and glycogenolysis (breakdown) should not occur simultaneously (futile cycle).
Intermediates in glycolysis used for other reactions.

Four Main Regulatory Methods

Energy Status
- High ATP: Glycolysis preferred (for intermediates or storage, not necessarily ATP production).
- Low ATP: Gluconeogenesis favored (to produce glucose for energy).
- Energy to do this comes from fats and lipids.
Enzyme Control
- Hexokinase (first step of glycolysis) inhibited by Glucose-6-Phosphate.
- Substrates and inhibitors regulate enzyme activity.
- Enzyme modification (denaturation, active site changes).
Hormonal Control
- Insulin: signals cells to take up glucose.
- Promotes glycogen synthesis and inhibits glucose production.
Allosteric Regulation
- Chemical inhibitors to enzymes.
- Enzyme modification (acetylation).
- Gene expression (methylation/acetylation of DNA to turn genes on/off).

Other Sugars

Body converts various sugars into glucose.
Lactose $\rightarrow$ Galactose + Glucose.
Fructose can enter glycolysis directly (skipping initial steps).
Glycerol (3-carbon sugar) can enter glycolysis.
Burning fat generates building blocks for making glucose.
Sucrose (glucose + fructose).

Practice Questions

Pass Level

What organ in the body has the highest need for glucose?

Credit/Distinction Level

What enzyme/chemical/compound is likely to be involved in the process shown below from malate to oxaloacetate in the citric acid cycle?
- Answer: $NAD^+$

High Distinction Level

You go out to dinner in an Italian restaurant, you have a garlic bread entree followed by a large Cabanara main with linguine pasta. For dessert, you have a big bowl of low fat gelato. What happens in your body to the glucose and glycogen levels?
- Complex carbs -> lots of sugar.
- Low fat gelato -> simple sugar.
- Sugars are rapidly absorbed, lead to high blood sugar.
- Body has to deal with excess sugar by storing it as glycogen. The glucose levels in body goes up.