Glycolysis occurs in the
Cytosol
Net ATP produced in glycolysis
2 (2 used in first stage, 4 made in second (2each made by both three carbons molecules))
Glucose transporters
- GLUT 1: all mammalian tissues (basal glucose uptake)
- GLUT 2: liver and pancreatic B cells (regulation of insulin in pancreas, removes excess glucose from blood in liver)
- GLUT 3: all mammalian tissues (basal glucose uptake)
- GLUT 4: muscle and fat cells
- GLUT 5: small intestine (fructose transporter)
Kinase
phosphorylate biomolecules using ATP as the phosphate donor
Isomerization rxn
No atoms lost —> only a rearrangement of the atoms occurs
Bisphosphate means 2 separate monophosphoryl groups are present
Diphosphate means two phosphoryl groups are present and are connected by an anhydride linkage
Dehydrogenases
Enzymes that catalyze redox reactions
Mutases
Isomerases that reposition phosphate groups in a molecule
Net rxn for glycolysis
Glucose + 2 Pi + 2 ADP + 2 NAD+ —> 2 pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O
-22kj/mol
Metabolism of pyruvate (diff metabolic fates)
Need to regenerate NAD+ consumed by glyceraldehyde-3-P dehydrogenase
- ethanol (first converted to acetaldehyde by pyruvate decarboxylase —> acetaldehyde reduced to ethanol by alcohol dehydrogenase) —> no net redox —> fermentation
- lactate (pyruvate reduced to lactate by lactate dehydrogenase) - as lactate builds up in muscle during anaerobic conditions, fatigue sets in cuz ph goes down and inhibits pfk (so glucose can’t be metabolized for energy)
- acetyl CoA (NAD+ noT regenerated, but more is consumed for the CA cycle)
Fructose
- Component of sucrose (table sugar) and also in corn syrup (sweetener)
Galactose
Component of lactose (milk sugar)
Galactose entry into glycolysis
Converted to G6P and enters
- Phosphorylation of galactose
- Transfer of galactose to an activated carrier (UDP)
- Rearrangement of one hydroxyl group on galactose to form glucose by epimerase (isomerase that repositions hydroxyl groups)
- Glucose-1-P converted to G6P by phosphoglucomutase
Lactose intolerance
- 75% of world population
- deficiency in lactase in small intestine, which breaks down lactose into glucose and galactose
Fructose entry into glycolysis
Metabolized in liver:
- Fructose phosphorylated to F1P by fructokinase in liver
- F1P split into two 3-carbon sugars, dihydroxyacetone phosphate and glyceraldegyde by a F1P aldolase
- Glyceraldehyde phosphorylated to glyceraldehyde 3 phosphate by triose kinase
Excessive fructose consumption leading to obesity, fatty liver and type 2 diabetes
Bypasses PFK main regulatory point, causing uncontrolled flow of metabolites through glycolysis —> excessive amounts of pyruvate, converted to acetyl CoA, converted to fatty acids —> fatty liver (lighter and causes cirrhosis and liver failure)
Glycolysis roles
- degrade glucose to generate ATP
- provide building blocks for biosynthetic processes (such as formation of glycogen, fatty acids, amino acids)
Glycolysis regulation enzymes
Hexokinase, PFK, pyruvate kinase
Why is hexokinase not the major point of control when it’s the first step in glycolysis
Phosphorylation of glucose to G6P is not the first committed step for this pathway —> G6P can enter other pathways like the PPP and glycogen synthesis
Alcoholic fermentation
A metabolic pathway that generates ethanol from pyruvate through decarboxylation and reduction
Feedback inhibition
The inhibition of an early step in a pathway by the product of a later step
Feedforward stimulation
Activation of a later step in a pathway by the product of an earlier step
Glycolysis
A 10 reaction pathway by which glucose is metabolized to 2 molecules of pyruvate with the generation of 2 molecules of ATP and 2 molecules of NADH
Substrate level phosphorylation
Direct transfer of a phosphoryl group in a biomolecule to ADP to generate ATP
