Glycolysis
What is the rate-limiting enzyme in glycolysis?
PFK-1
catalyzes fructose-6-phosphate to fructose-1-6-bisphosphate
inhibited by ATP and citrate
not inhibited by AMP
Main anaerobic glycolysis step?
Pyruvate to Lactic acid
Catalyzed by LDH
infection/hypoxia/HF
testes/lens/wbc/rbc/cornea/kidney
Goal of this shunt? what does it produce
PRODUCE NADPH
required for glutathione reduction, which is required for free radical detoxification
Which enzyme reduces glutathione from its oxidized form?
glutathione reductase
goal: catalyze H2O2 to H2O (free radical detox)
recall what cofactor do you need?
Two main enzymes to know?
Fructokinase (fructose to f-1-p)
Aldolase B (f-1-p to glyceraldehyde/DHP)
Glucokinase/hexokinase catalyze which step
hexokinase has higher affinity and lower Km than glucokinase
Glucokinase: acts as a glucose sensor, only uses glucose at high conc, only in liver and pancreatic beta cells
Hexokinase: Basal glucose metabolism, ALL tissues
pyruvate carboxylase vs pyruvate dehydrogenase
PC catalyzes pyruvate to oxaloacetate
PD catalyzes pyruvate to acetyl-coa for use in TCA
BOTH OCCUR IN MITOCHONDRIA
Which glycolysis step shunts to pentose phosphate pathway
glucose-6-phosphate catalyzed by G6PD to 6-phosphogluconolactone
requires NADP+ to produce NADPH, meeting the shunt's goal
What happens when we have decreased NADPH
decreased reduced glutathione --> oxidative stress
causes of oxidative stress:
fava beans, sulfa drugs, infection, primaquine, nitrofurantoin
which deficiency is benign?
fructokinase deficiency
fructose in blood/urine
inheritance?
What is the alternative pathway for fructose-6-phosphate
fructose-2-6-bisphosphate (catalyzed by PFK-2)
Insulin promotes this, glucagon inhibits
(still breaking down glucose at this point)
pyruvate dehydrogenase cofactors
B1,B2,B3,B5, lipoic acid
Where does HMP pathway occur in cells and in what organs?
Cytoplasm
H: hepatic
M: mammary glands
P: periphery of adrenals
What disease/deficiency results in reduced NADPH
G6PD deficiency
inheritance?
hereditary fructose intolerance deficiency?
aldolase b deficiency
what is accumulated?
What catalyzes the last step of glycolysis (PEP to pyruvate)
pyruvate kinase
Alanine aminotransferase pathway from pyruvate
ALT and B6 catalyze pyruvate (muscle) to alanine (liver)
G6PD deficiency on blood smear
Heinz bodies (denatured hemoglobin) --> bite cells (phagocytic clearance) by splenic macrophages
HFI treatment?
dont ingest fructose/sucrose/glucose
what inhibits pyruvate kinase?
ATP and citrate
negative feedback
Cahill cycle
Goal: recycle carbons between muscle and liver
reversible pyruvate to alanine to glucose rxns back and forth between muscle and liver
glucose levels in HFI?
hypoglycemia after ingesting candy, juice, etc
f-1-p cant go anywhere, atp is depleting, body needs atp to do gluconeogenesis
--> low blood sugar