Glycolysis Flashcards
Fate of absorbed glucose - how does glucose in the bloodstream enter cells?
via specific transporters (GLUT) by facilitated diffusion!
Where is glucokinase found? what it its Km for glucose?
in liver and beta cells of pancrease
km is high (needs way more glucose to get saturated) = which is why its more active when BGL are elevated
what is hexokinases Km for glucose?
low Km = high affinity!
after glucose is phosphorylated and becomes glucose-6-phophate, what are the intracellular fates of glucose-6-phosphate in the liver?
glycogen
pyruvate
HMP shunt
where are glycolytic enzymes present>
in the cytosol
what are the 3 general stages of glycolysis
Stage 1: energy investment stage
stage 2: cleavage of 6C sugar to 3C intermediates
stage 3: energy generation phase
How many reactions are involved in stage 1?
2 phosphorylation reactions
requires 2 ATP
what is the second irreversible reaction of glycolysis?
PFK1 - phosphofructokinase-1
also the most important regulated step (allosteric regulated enzyme)
Where are aldolase A and B found?
muscle and liver
how many molecules of pyruvate are formed in glycolysis?
2 pyruvate
what does glyceraldehyde-3-phosphate dehydrogenase result in the formation of?
NADH
what does phosphoglycerate kinase result in the formation of?
the first ATP (substrate level phosphorylation)
why are 1,3 BPG and phosphpenolpyruvate special?
they are both high energy intermediates and compounds, respectively. they can form ATP within the involvement of the ETC in mitochondira
what does pyruvate kinase result in?
formation of the 2nd ATP
what are the fates of pyruvate?
aerobic –acetyl coA(pyruvate dehydrogenase)–enters TCA cycle
anaerobic –lactate(lactate dehydrogenase)–goes to liver via Cori cycle
also in liver–gluconeogenesis(pyruvate carboxylase) –oxaloacetate
what are the 3 irreversible reactions in glycolysis?
glucokinase/hexokinase
phosphofructokinase 1
pyruvate kinase
what were the two substrate level phosphorylation reactions in glycolysis?
phosphoglycerate kinase
pyruvate kinase
what is the overall reaction of aerobic glycolysis?
aerobic
how many ATP are formed in aerobic glycolysis?
8 ATP
how many ATP are formed in anaerobic glycolysis?
2 ATP
what are inhibitors of glycolysis?
arsenate and fluoride
why does fluoride have to be added to blood collection tube in clinical labs?
if fluoride wasn’t added - there would be a reduction in the glucose due to its utilization by RBC and WBC, resulting in an erroneously low value for blood glucose
what is the significance of glycolysis in tissues which complete oxidation takes place
brain, skeletal muscles - glucose is converted to pyruvate, that is later converted to acetyl coA that enters the TCA cycle for complete oxidation of glucose
why is glycolysis significant in adipose tissue?
glyceraldehyde-3-phosphate (provides glycerol component) that is used for TAG formation
why is glycolysis significant for RBC?
anaerobic glycolysis is the major source of energy - forms 2,3 BPG
glycolysis also important in retina, lens and
tumor cells
when does 2,3 BPG increase?
when a person moves to a high altitude - facilitates unloading - right shift
what is hemolytic anemia?
RBC PK deficiency
second most common form of hemolytic anemia
what is the most common form of hemolytic anemia?
G6PD definicieny
what is lactic acid an example of?
metabolic acidosis - commonly seen
when is lactic acid observed?
increase conversion of pyruvate to lactate (increase NADH/NAD+ ratio)
strenuous muscle activity
inherited deficiency of pyruvate dehydrogenase (leigh disease)
thiamine deficiency = lowered activity of pyruvate dehydrogenase
defect in gluconeogensis (decrease conversion of lactate to glucose)
decreased blood supply results in anaerobic metabolism in the peripheral tissues
what do cancer cells used as the main source of ATP?
glycolysis - ‘Warburg effect’
what do tumor cells utilize in PET scans?
fluorodeoxyglucose (FDG)
pharmacological inhibitor of glycolysis are explored for use as therapeutic agents in variety of cancers
what is galactose deficiency
galactosemia/galactosuria, cataracts in childhood (excess galactose is converted to galatitol via aldose reductase)
Treatment: no galactose in diet
what is Gal-1-P uridyl transferase deficiency?
same as galactokinase deficiency but more severe with vomiting/diarrhea after milk ingestion, liver disease, lethargy mental retardation,
Tx=no galactose in diet
what is fructoinase deficiency?
fructosuria - benign
what is aldolase B deficiency?
fructosuria - liver and prominal renal tubule disorder
tx = no fructose in diet
pyruvate kinase deficiency?
chronic hemolysis, you increase 2,3 BPG and other intermediates in the RBX - autosomal recessive
what inhibits HK?
g-6-p = product inhibition
what stimulates GK?
insulin in the liver
what activates PFK-1?
AMP
F-2,6-bisP
what inhibits PFK-1?
ATP
Citrate
what activates PFK-2?
insulin
what inhibits PFK-2?
glucogon
what activates PK?
F-1,6-bisP
insulin
what inhibits PK?
ATP
Acetyl Co A
Alanine
Glucagon
what does GLUT 1 + 3 transporters do?
basal uptake - neurons and brain
What does GLUT 2 transporters do?
liver
what does Glut 4 transporters do?
adipose and muscle
why is glucokinase needed in the liver?
to reduce high BGL after a large meal
what does glucokinase do in the pancreas?
recognition of high BGL and –> insulin release
genetic deficieicny of GK can lead to what?
DM in the young type 2 (MODY 2)
where is GK stored at high fructose 6-P levels?
nucleus
what is important to remember about exercising muscle and AMP levels
high levels of AMP overcome inhibition by ATP
