44. Glycolysis Flashcards
major pathway for glucose metabolism that converts glucose into 3 carbon compounds to provide energy
glycolysis
where does glycolysis occur
cytosol of all mammalian cells
what is the substrate of glycolysis?
glucose
what are end products of glycolysis
2 molecules of either pyruvate or lactate
rate limiting step of glycolysis
fructose-6-phosphate –> fructose-1,6- biphosphate
enz. Phosphofructokinase-1
important steps of glycolysis
- glucose -> glucose-6-phosphate
enz. hexokinase/ glucokinase
fructose-6-phosphate
phosphorylation
fructose-6-phosphate –> fructose-1,6-biphosphate
PFK-1
PFK-2 product
fructose-2,6- biphosphate
PEP -> pyruvate
pyruvate kinase
2 steps of glycolysis produce ATP via substrate level phosphorylation
(1) 1,3-biphosphoglycerate –> 3-phosphoglycerate
enz. phosphoglycerate kinase
(2) phosphoenolpyruvate –> pyruvate
enz. pyruvate kinase
production of NADH in glycolysis
glyceraldehyde-3-phosphate –> 1,3 biphosphoglycerate
enz.glyceraldehyde-3-phosphate dehydrogenase
this enzyme can phosphorylate glucose and other hexoses is present in most tissues
hexokinase
glucokinase is present in
- liver parenchymal cells
* islets of pancreas
hexokinase is inhibited by
glucose-6-P
glucokinase is inhibited by
fructose-6-P
- this enzyme can phosphorylate glucose and other hexoses
- low Km,high affinity
- low Vmax
hexokinase
- this enzyme can phosphorylate glucose and other hexoses
* induced by insulin
glucokinase
•this enzyme can phosphorylate glucose and other hexoses
- High km, low affinity
- high Vmax
glucokinase
activator of PFK-1
- fructose-2,6-BP
* AMP
activator of PFK-2
- well fed state
- ÎÎ insulin
- dec glucagon
inhibitor of PFK-1
- citrate
* ATP
inhibitor of PFK-2
- fasting state
- dec insulin
- inc glucagon
how many ATP is yielded per molecule of PEP
1 ATP
PEP -> pyruvate
enz. pyruvate kinase
activated by?
fructose-1,6-BP
PEP -> pyruvate
enz. pyruvate kinase
inhibited by?
glucagon
type of glycolysis
- cells without mitochondria
- cells without sufficient O2
anaerobic glycolysis
type of glycolysis
•cells with mitochondria
•with adequate O2 supply
aerobic glycolysis
end product of anaerobic glycolysis
lactate
end product of
aerobic glycolysis
pyruvate
used to reduce pyruvate to lactate
NADH
major fate of pyruvate in lens, cornea, eye, kidney, medulla, testes, RBCs,WBCs
anaerobic glycolysis
lactic acidosis is seen in
- vigorous exercise
- septic shock
- cancer cachexia
NADH to pass through inner mitochondrial membrane requires
•glycerophosphate shuttle
or
•malate aspartate shuttle
ATP yield with glycerophosphate shuttle
1 NADH = 1.5 ATPs
ATP yield with
malate aspartate shuttle
1 NADH = 2.5 ATPs
this shuttle of NADH is found in
most tissues and heart muscle
malate aspartate shuttle
this shuttle of NADH is found in
brain and white muscle
glycerophosphate shuttle
net ATP yield
aerobic glycolysis
5 or 7
net ATP yield with anaerobic glycolysis
2 ATP
thhis is found in RBCs where rxn catalyzed by phosphoglycerate kinase is bypassed
2,3-biphosphoglycerate
1,3- BPG –> 2,3-BPG
enz. biphosphoglycerate mutase
Fates of Pyruvate :
- Anaerobic glycolysis
•lactate (lactate dehydrogenase) - Gluconeogenesis
•oxaloacetate (pyruvate carboxylase) - Citric acid cycle
•acetyl coa (pyruvate dehydrogenase) - Fermentation
•Ethanol (pyruvate decarboxylase)
pyruvate –> acetyl coa
pyruvate –> acetyl coa
enzyme: pyruvate dehydrogenase complex
co-enzymes:
- thiamine pyrophosphate
- FAD
- NAD+
- coenzyme A (pantothenic acid)
- lipoic acid
most common enzyme defect in glycolysis
pyruvate kinase deficiency
provide lipids as alternative fuel
in the muscle
muscle phosphofructokinase
most common cause of congenital lactic acidosis
pyruvate dehydrogenase deficiency
inheritance of pyruvate dehydrogenase deficiency
X-linked dominant
clinical manifestations of pyruvate dehydrogenase deficiency
- lactic acidosis
* brain : ÎÎ lactate , decrease acetyl COA -> brain deprivation of acetyl CoA -> psychomotor retardation and death
tx pyruvate dehydrogenase deficiency
ketogenic diet
aldolase A deficiency manifests as
hemolytic anemia
pyruvate kinase deficiency leads to
hemolytic anemia
mutations that dec activity of glucokinase leads to
Maturity onset diabetes of the young, type 2
Maturity onset diabetes of the young, type 2
due to glucokinase dec activity
tx
majority no tx required
except during pregnancy
arsenic poisoning competes with
inorganic phosphate as a substrate
for glyceraldehyde-3-P dehydrogenase
chronic alcoholism effect on tiamine
inhibits absorption
cause fatal pyruvic and lactic acidosis
