Glycolysis: Functions, pathways, energetics, regulation- Lecture 61 Flashcards
What is the overall reaction of glycolysis?
C6H12O6 + 2NAD+ + 2 Pi –> 2 CH3COCOOH (pyruvate) + 2 ATP + 2 NADH
Gycolysis is the only source of energy for ________ and a major source of energy for _________.
RBCs and normally for the brain
Embryonic tissue, retina, adrenals, some immune cells, exercising muscles
What is the first step of glycolysis?
Glucose + ATP –> Glucose-6-Phosphate + ADP + Pi
via hexokinase
Which steps in glycolysis are irreversible?
1, 3, and 10
What is the second step of glycolysis?
G6P –> Fructose 6-P
via phosphoglucoisomerase
What is the third step in glycolysis?
F6P + ATP –> F1,6bisP + ADP
via phosphofructokinase
RATE LIMITING
What regulates the rate limiting step of glycolysis (not in the liver)?
the third step of glycolysis is catalyzed by PFK which is…
inhibited by ATP and citrate
stimulated by AMP, Pi, NH4, F1,6bisP
What kinds of sites does PFK have?
two substrate binding sites (ATP, F6P)
two allosteric inhibitory sites
four allosteric activator sites
What regulates the rate limiting step of glycolysis (in the liver)?
the third step of glycolysis is catalyzed by PFK which is…
insulin stimulates
glucagon inhibits
What is the fourth step of glycolysis?
F1,6bisP < —- > DHAP + G3P
via aldolase
What is the fifth step of glycolysis?
DHAP < —- > G3P
via tripse phosphate isomerase
*note that after this you have two G3P products which can continue (so everything after this step should be doubled)
What is the sixth step of glycolysis?
G3P + NAD+ + Pi < —- > 1,3 bis phosphoglyceric acid + NADH
via gluceraldehyde 3-P dehydrogenase
Note: oxygen independent
_____ is a high energy compound that “traps” energy that would have otherwise been ______.
1,3 bis PGA
released as heat
What is the seventh step of glycolysis?
1,3 bis PGA + ADP < —- > 3 PGA + ATP
via phosphoglycerate kinase
What is substrate level phosphorylation?
the transfer of energy to a high energy intermediate which can produce ATP
_____ is highly sensitive to poisoning by heavy metals such as _____.
Phosphoglycerate kinase (enzyme of glycolysis 7) Hg, Cd, Pb
What effect does arsenic have on the body?
competes with Pi for G3P in the G3PDH reaction to form arseno-3-phophoglyceric acid rather than 1,3 bisP that releases energy as heat rather than as ATP
glycolysis continues, but no ATP is produced- this is a problem in RBCs who use this as their only source for ATP –> anemia
RBCs have a mutase which converts small amounts of ______ into ________, an important allosteric effector of hemoglobin that regulates _____.
1,3 bis P
2,3 bis P
oxygen affinity
What is the eighth step of glycolysis?
3 phosphoglycerate < —- > 2-phosphoglycerate
via phosphoglyceromutase
What is the ninth step of glycolysis?
2PGA < —- > Phosphoenolpyruvate (PEP)+ H2O
via enolase
Enolase is inhibited by ______.
fluoride
What is the tenth step of glycolysis?
PEP + ADP –> Pyruvate + ATP
via pyruvate kinase
Which steps of glycolysis participate in substrate level phosphorylation?
seven and ten
How is pyruvate kinase regulated?
inhibited by ATP, NADH, and acetyl CoA
stimulated by F1,6 bis P
inhibited by glucagon(Epi) cAMP-PKA phosphorylation
stimulated by insulin
What is the net ATP yield for one mol of glucose through glycolysis?
net 2 ATP
2 ATP consumed, 4 ATP produced
Describe fructose metabolism in the liver.
- Fructose + ATP –> Fructose 1P
via fructokinase - Fructose 1P –> Glyceraldehyde + Dihydroxyacetone P
via aldolase - Glyceraldehyde + ATP –> Glyceraldehyde 3P + ADP
via triose kinase - G3P –>–> Pyruvate
What is hereditary fructose intolerance?
Aldolase B in liver is replaced by aldolase A which cannot react with Fructose 1P
Describe the pathway of galactose metabolism.
- Galactose + ATP –> Galactose 1P + ADP
via galactokinase - Galactose 1P + UDP-glucose –> Glucose 1P + UDP-galactose
via galactose 1P uridylyltransferase - glucose 1P –> glucose 6P
via phosphoglucomutase - Glycolysis (other tissues) or return to glucose (liver)
What is galactosemia?
mainly deficiency of galactose 1P resulting in accumulation or toxic galactose 1P uridylytransferase in liver, may also be caused by deficiency of galactokinase