Glycolysis

Salivary α-amylase

Where

Type

Reaction

1. Where - Mouth

2. Type - Endo-glucanase

3. Reaction - Hydrolizes internal α1→4 glycosidic bonds in starch and glycogen

Pancreatic α-amylase

Where

Reaction

1. Where - SI

2. Reaction - Creates maltose, glucose, and dextrins

Surface-bound enzymes

Where

Types

1. Where - Brush border of SI epithelial cells

2. Types - Dextrinase, maltase, sucrase, and lactase

Dextrinase function

Hydrolysis of α1→6 glycosidic bonds, releasing glucose

Maltase function

Hydrolysis, releasing two glucose molecules

Sucrase function

Hydrolysis, releasing glucose and fructose

Lactase function

Hydrolysis of β1→4 glycosidic bonds, releasing glucose and galactose

Why is glycolysis the first metabolic pathway we examine? (3)

1. Occurs in nearly every cell type

2. Cystolic - doesn't require organelles

3. Functions aerobically and anaerobically

How does mannose enter glycolysis? (2)

1. Mannose → mannose-6-phosphate

2. Mannose-6-phosphate → fructose-6-phosphate

How does galactose enter glycolysis? (2)

1. Galactose → glucose-1-phosphate; Leloir pathway

2. Glucose-1-phosphate → glucose-6-phosphate

How does fructose enter glycolysis via muscle and adipose tissue

Fructose → fructose-6-phosphate; hexokinase

How does fructose enter glycolysis via liver (3)

1. Fructose → fructose-1-phosphate; fructokinase 

2. Fructose-1-phosphate → DHAP + glyceraldehyde; aldolase B 

3. Glyceraldehyde → Glyceraldehyde-3; tyrosine kinase

Substrate-level phosphorylation definition

Enzyme-catalyzed transfer of a phosphoryl group from a substrate to ADP

Allosteric modulators of Phosphofructokinase-1 (PFK-1) (3)(2)

1. Activate:

   1. AMP

   2. ADP

   3. Fructose-2,6-bisphosphate

2. Inhibit:

   1. ATP

   2. Citrate

Allosteric modulators of pyruvate kinase (2)

1. Inhibit:

   1. ATP

   2. Alanine

Allosteric modulators of hexokinase (1)

Inhibit - glucose-6-phosphate

Insulin and glycolysis (2)

1. Stimulates glycolysis

2. Activates PFK-2, producing Fructose-2,6-bisphosphate which activates PFK-1

Glucagon and glycolysis

1. Inhibits glycolysis by activating PKA

2. PKA phosphorylates and inhibits pyruvate kinase, decreasing Fructose-2,6-bisphosphate

3. A decrease in Fructose-2,6-bisphosphate inactivates PFK-2

PFK1 and PFK2 in Low energy charge

PFK-2 activated = Lower Km for fructose-6-phosphate = More fructose-2,6-bisphosphate produced

PFK1 and PFK2 in neutral energy charge

Both PFK-1 and PFK-2 activated = Same Km = More PFK-1 than PFK-2 = More fructose-1,6 bisphosphate produced

PFK1 and PFK2 in high energy charge

Citrate activated = Fructose-2,6-bisphosphate → fructose-6-phosphate; PFK-2 = PFK-1 inhibited = Decreased glycolysis

Phosphorylation of PFK1 vs PFK2

1. PFK-1 is activated via phosphorylation 

2. PFK-2 is activated via dephosphorylation

The two fates of pyruvate after glycolysis

Aerobic

Anaerobic

Pyruvate under Aerobic conditions

1. Enters mitochondria

2. Pyruvate → acetyl-CoA; Pyruvate dehydrogenase complex

Pyruvate under Anaerobic conditions

1. Pyruvate → lactate; Lactate dehydrogenase

2. Regenerates NAD+

Why is the regeneration of NAD+ important in anaerobic glycolysis?

Sustains glycolysis, allowing Glyceraldehyde-3-phosphate to produce NADH

Lactate dehydrogenase (LDH) Km values (2)(2)

1. LDH-M (muscle) = Higher Km for pyruvate = Lower affinity

   1. Pyruvate → lactate under anaerobic conditions

2. LDH-H (Heart) = Lower Km for pyruvate = Higher affinity

   1. Lactate → pyruvate under aerobic conditions