GLYCOLYSIS

GLYCOLYSIS
Converting (1) glucose to (2) pyruvates Cytosolic Occurs in almost all living organisms
ref: Chapter 18 Garrett and Grisham

Divided into two phases The energy consuming phase and the energy yielding phase
Five reactions in each phase Per glucose molecules 2 ATPs are consumed in the first part & 4 ATPs and 2 pyruvates produced in the second part.

GLYCOLYSIS
Energy consumption phase
Production of glucose-6-phosphate ATP is consumed - 1st priming step. Catalysed by either : hexokinase -low Km[glucose] or glucokinase (liver enzyme) -high Km[glucose] Enzyme levels regulated by insulin

GLYCOLYSIS
Energy consumption phase Phospho-gluco-isomerase
Fructose-6-phosphate synthesis
Aldose-ketose isomerization Prepares C1 for second phosphorylation Prepares C3 for eventual cleavage.

Advantages to phosphorylated sugar

impermeable - retained in the cell glucose concentration gradient retained glucose carbon skeleton committed to metabolism

GLYCOLYSIS
Energy consumption phase
Phospho-fructo-kinase reaction
(2nd ATP consumption step) Commits carbon skeleton to glycolysis Allosteric regulation Inhibitors ATP: increases Km[fructose-6-Pi]
Activators& citrate AMP reverses inhibition by ATP & F-2,6-BP: increases affinity for F-6-P decreases ATP inhibition

GLYCOLYSIS
Energy consumption phase
Aldolase
Catalyses formation of DHAP and glyceraldehyde-3-P from F1,6-BisP

Triose phosphate isomerase

Catalyses inter-conversion of DHAP and glyceraldehyde-3-P

GLYCOLYSIS
Energy yielding phase
Glyceraldehyde-3-phosphate dehydrogenase
Synthesizes 1,3-bisphosphoglycerate Adds a phosphate, reduces NAD+ to NADH Glyceraldehyde is oxidized to glycerate Site of arsenate poisoning

GLYCOLYSIS
Energy yielding phase
Phosphoglycerate kinase
ATP and 3-PGA produced Substrate level phosphorylation

Phospho-glycero-mutase
3-PGA converted to 2-PGA

GLYCOLYSIS
Energy yielding phase
Enolase 2-PGA is converted to phosphoenolpyruvate Dehydration reaction

GLYCOLYSIS
Energy yielding phase
Pyruvate kinase
Second energy harvesting reaction ATP produced by substrate level phosphorylation Reaction regulated by: Activated by AMP and F-1,6-BP Inhibited by ATP, acetyl CoA, alanine Covalent phosphorylation inhibits pyruvate kinase

GLYCOLYSIS
FATE OF NADH & PYRUVATE
Aerobic respiration
Eukaryotes - pyruvate transported into mitochondria converted to acetyl CoA and enters the TCA cycle converted to citrate. NADH -high energy electrons transported into mitochondria and electrons fed into electron transport chain.

GLYCOLYSIS
FATE OF NADH & PYRUVATE
Anaerobic respiration. Lactic acid fermentation
Pyruvate converted to lactate regenerates NAD+

Alcoholic fermentation
Pyruvate converted to acetaldehyde Acetaldehyde converted to ethanol and NAD+ regenerated.

Anaerobic respiration Both pyruvate and NADH feed into fermentationlactic acid fermentation or alcoholic fermentation.

GLYCOLYSIS
FATE OF NADH & PYRUVATE
High energy electrons can be transported across inner mitochondrial membrane by Glycerol-3-phosphate shuttle or Malate-aspartate shuttle.
Different energy yields depending on which shuttle used.

GLYCOLYSIS
Students should be able to answer tutorial questions See separate file.

Lactose intolerance
Lactose = glucose - galactose
Lactase is an inducible enzyme in mammals - activity peaks shortly after birth but declines to low levels by the age of 5. Low levels of lactase make many adults lactose intolerant.

Galactose metabolism
Lactose is hydrolyzed to glucose and galactose. [Glucose is metabolized via glycolysis] Galactose is activated by galactokinase to galactose 1phosphate Galactose-1-phosphate is converted to UDP-galactose by reacting with UDP-glucose releasing glucose-1-phosphate and UDP-galactose Glucose-1-phosphate is then converted to glucose-6phosphate and enters glycolysis. UDP-galactose is converted to UDP-glucose and reacts with another molecule of galactose-1-phosphate

Sucrose metabolism
Sucrose = glucose + fructose
Sucrose is hydrolysed by invertase releasing glucose and fructose. Glucose metabolized via glycolysis. Fructose is activated by fructokinase to fructose-1-phosphate. Fructose-1-phosphate conversion to dihydroxyacetone phosphate and glyceraldehyde is catalyzed by aldolase B. Glyceraldehyde is converted to 3-phosphoglyceraldehyde (triose kinase) which is then metabolised via the energy harvesting reactions of glycolysis. Fructose metabolism leads to fats - no regulation of fructose metabolism at phosphofructokinase.