Glycolysis/Gluconeogenesis Flashcards
Oxidation
breaking down bonds and releasing energy
Biologically irreversible reaction
Delta G is so negative (-6kCal/mole or more) that the reverse reaction cannot occur bc the energetic roadblock is too high
Catabolic
break bonds and release energy (oxidative and degradative reactions)
Anabolic
making bonds
- requires energy (reductive and biosynthetic reactions)
Preparatory Phase
- requires 2 ATP
- two biologically irreversible steps
- glucose to glyceraldehyde 3 phosphate
Energy producing phase
- oxidation step
- one biologically irreversible step
- glyceraldehyde 3 phosphate to pyruvate
glucose phosphorylation
glucose to glucose 6-phosphate
- enzyme = hexokinase
- enzyme needs Mg+2 to neutralize neg charge density on ATP
- bio irreversible
Glucokinase
works with organs that handle large quantities of available sugar
- liver, kidney, intestine, and beta cells of pancreas
- low affinity for glucose
- matches blood glucose concentration after eating (50% active)
- regulated by GKRP and F-6-P
- excess F-6-P drives glucokinase back into inactive complex in nucleus
Hexokinase
- predominant enzyme in most cells
- has very high affinity for glucose
- feedback inhibited by G-6-P
Glucokinase regulatory protein
- activated by F-6-P
- excess F-6-P drives complex formation of glucokinase with GKRP back into inactive form in nucleus
Isomerization of Glucose 6 phosphate
- moving electrons
- enzyme = phosphohexose isomerase
- product = fructose 6 phosphate
Phosphorylation of Fructose 6 phosphate
- product = fructose- 1,6- bisphosphate
- major site of metabolic regulation
- 2nd biologically irreversible rxn
- enzyme = phosphofructokinase 1 (PFK1)
cleavage of F-1,6-P2 into DHAP and glyceraldehyde 3 phosphate
-enzyme = aldolase
aldolase
- enzyme that uses F-1,6-P2 or DHAP + glyceraldehyde-3-P as substrates
- Aldolase A: muscle and red blood cells
- Aldolase B: liver (will use F-1-P as substrate)
- Aldolase C: brain
oxidation of glyceraldehyde-3-P
- this step is activating inorganic phosphate in order to make ATP
- NAD is reduced
- energy released in oxidation is used to convert low energy phosphate to a high energy, unstable mixed anhydride
Nicotinamide Coenzymes
- derived from Niacin
- NAD(H) = catabolic pathways
- or NADP(H) = anabolic pathways
- niacin deficiency leads to pellagra
2,3-bisphosphoglycerate
- needed to keep phosphoglycerate mutase active
- used in RBC to act as allosteric regulator of hemoglobin (binds to hemoglobin and lessen its affinity to oxygen so oxygen can be delivered to body)
Regulation of Pyruvate Kinase
- activated by fructose-1,6-bisphosphate
- inhibited by ATP
- in liver, covalent phosphorylation by PKA (cAMP) intensifies inhibition of ATP
Brain glycolysis
aerobic glycolysis
- uses glucose
Muscle glycolysis
either aerobic or anaerobic
- redder the muscle = more mitochondria it has and the more oxidative metabolism it can rely on
red blood cell glycolysis
anaerobic glycolysis
- no mitochondria (can’t do Krebs cycle and Ox. Phos.)
- lactate is produced and dumped into the blood
Liver glycolysis
glycolysis is an energy storing pathway in the liver as it releases glucose into the body when blood glucose levels are low
- derives energy from oxidation of fatty acids
- aerobic
gluconeogenesis
largely takes place in the liver
re-synthesis of glucose
substrates: amino acid carbon skeletons, glycerol, and lactate
Glucose-6-phosphatase
- hydrolytic enzyme that takes phosphate off a molecule
- occurs in the endoplasmic reticulum
- a defect in any of the subunits will prevent glucose from leaving the liver and result in von Gierke’s disease (glycogen storage disease type I)
