Glycolysis Feeder Pathways

• Feeder pathways supply glycolysis with fuel
• These pathways ensure glycolysis has a continuous supply of carbohydrates, regardless of the source

Feeder Pathways Overview

• Glycolysis requires carbohydrates, and feeder pathways make sure these are available

Types of Carbohydrates

• Glycogen
• Starch
• Trehalose
• Sucrose
• Lactose

Glycolysis Entry Points

• Carbohydrates enter glycolysis through several points
• Carbohydrates are not limited to entering glycolysis as glucose
• Carbohydrate entry varies; some enter as glucose-6-phosphate (G6P), others as fructose-6-phosphate (F6P)
• Not all carbohydrate types have the same entry point into glycolysis

Initial Digestion

• Digestion begins through chewing and saliva
• Creates a mechanical and chemical breakdown

Amylase Activity

• Food goes to the stomach where mechanical digestion from chewing and chemical digestion from saliva begins
• Amylase enzyme activity stops in the stomach because it cannot handle the acidity
• Further amylase is secreted by the pancreas and acts in the small intestine

Hydrolytic Enzymes

• Hydrolytic enzymes break down oligosaccharides into smaller units

Entry of Glycogen

• Glycogen enters glycolysis after being broken down into glucose monomers

Trehalose

• The enzyme trehalase is required for the breakdown of trehalose

Lactose

• The enzyme lactase is required for the breakdown of lactose

Sucrose

• The enzyme sucrase is required for the breakdown of sucrose

Glycogen and Starch

• Both glycogen and starch are storage forms of glucose
• Glycogen is stored in muscles and the liver
• Glycogen is broken down when glucose levels are low

Phosphorylase

• Phosphorylase is the enzyme that helps mobilize glycogen for glycolysis

Fructose Metabolism

• Fructose used by muscles differs from that used by the liver

Glycogen Structure

• Glycogen has many branches and is globular

Glycogen Breakdown

• Glycogen phosphorylase removes glucose units from the nonreducing ends of glycogen
• Inorganic phosphate (Pi) attacks the glycosidic bond in glycogen with the help of glycogen phosphorylase

Glucose-1-Phosphate

• A glucose molecule is released when glycogen is broken down shortening the original glycogen polymer
• Glucose-1-phosphate (G1P) is produced

Phosphorolysis

• Phosphorolysis breaks down glycogen into glucose-1-phosphate
• This process is distinct from hydrolysis

Energy Savings

• Breaking down glycogen by phosphorolysis saves energy (ATP) compared to starting glycolysis with free glucose

Glycogen Breakdown Advantages

• G1P conversion to G6P by phosphoglucomutase bypasses the ATP-consuming hexokinase step

ATP Consumption

• The hexokinase step consumes ATP during the initial glycolysis steps
• Using glycogen breakdown products effectively offsets the investment of ATP

Glycolysis Products

• Since breakdown of glycogen skips the initial ATP consuming steps more ATP is generated compared to glucose

Galactosemia

• Genetic defects in galactose metabolism cause galactosemia

Galactose Conversion

• Galactose converted to glucose-1-phosphate through several enzymatic steps

UDP-Glucose

• Defects in enzymes cause galactosemia and lead to high concentrations of galactose in blood and urine

Catalytic Consequences

• Infants with catalytic deficiencies often develop cataracts

Enzyme Deficiencies

• Transferase deficiency is a more severe form of galactosemia
• Characterized by poor growth, speech abnormalities, mental deficiencies, and liver damag

Lactose Intolerance

• Undigested lactose in the large intestine leads to bacterial fermentation
• This results in abdominal cramps and diarrhea

Pentose Phosphate Pathway (PPP)

• An alternative to glycolysis
• Also known as the phosphogluconate pathway or hexose monophosphate pathway

PPP Purpose

• Feeds into glycolysis, gluconeogenesis, and the pentose phosphate pathway

G6P

• 6-phosphate (G6P) can be used for glycolysis, gluconeogenesis, or the PPP

PPP Connection

• Two points of contact; can enter with a product of F6P or glyceraldehyde-3-Phosphate

Shunt

• PPP acts like a shunt, diverting and returning metabolites as needed

Regulation in PPP

• PPP is regulated primarily at the first step

Oxidative and Nonoxidative

• Pentose phosphate pathway consists of oxidative and nonoxidative phases

NADPH

• The oxidative phase generates NADPH, which is essential for cell function

Ribose-5-Phosphate

• The oxidative phase produces ribose-5-phosphate, a precursor for nucleotides

NADPH Usage

• NADPH is a reductant used in fatty acid biosynthesis, steroid synthesis, and cholesterol production

Maintaining Glutathione

• NADPH helps maintain glutathione in its reduced form, supporting antioxidant function

PPP and Glutathione

• Glutathione helps protect proteins by working as an antioxidant
• The production of NADPH is key

Nucleotide Biosynthesis

• In cells not needing ribose-5-phosphate, the nonoxidative phase recycles six pentose molecules into five hexose molecules
• This allows for continued NADPH production and glucose-6-phosphate conversion to CO2.

NADPH and Erythrocytes

• PPP is crucial for erythrocytes (RBCs)

Biosynthesis

• Generates NADPH crucial for fatty acids, cholesterol and catecholamines

Transparency

• Preserves transparency of eye lens because eye lens protein is actively reduced

Membrane Integrity

• Preserves erythrocyte integrity- prevents protein denaturation

Oxidative Stage

• Generates NADPH and converts G6P to ribulose-5-phosphate

Non-Oxidative Stage

• Recycles pentoses to maintain the oxidative phase

Ketolase and Transaldolase

• The 2 main enzymes active in this pathway

Tumors

• Because tumors multiply they require increased PPP activity, a side effect is increased glucose production

Regulation

• Higher levels of NADPH indicate reduced need for PPP, while lower levels activate PPP

Thiamine’s Role

• Thiamine is a component of TPP, hence deficiency leads to syndromes

ROS

• Reactive oxygen species and their detoxification

Antioxidant

• Antioxidant enzymes and molecules counteract ROS

NADPH and ROS

• The pentose shunt generates NADPH

Antioxidant Pathways

• NADPH enters antioxidant pathways

Glutathione

• Reduced glutathione helps prevent oxidation of iron in hemoglobin
• Important for transporting CO2

G6PD Deficiency

• Causes favism and jaundice as a result

Wernicke-Korsakoff Syndrome

• Wernicke-Korsakoff Syndrome is a disorder caused by a severe deficiency of thiamine, a component of TPP.
• Can lead to memory loss and paralysis