Lecture 5 - Introduction to Metabolism - Glycolysis II Flashcards
glucose carrier composition:
glucose carriers consist of a protein chain that crosses the membrane about 12 times and has at least 2 conformations - switch back and fourth
one conformation exposes the binding site to the outside of the cell and the other to the inside of the cell
human erythrocytes structure and how it alters theor form of ATP production:
•No mitochondria (no nucleus, and no other cellular organelles)
•Require ATP for Na+/K+ ATPase pump in keeping membrane potential which contributes to the maintenance of biconcave shape
•Relying entirely on glycolysis for ATP
•Glycolysis in the cytosol is the sole source of ATP
what are the different types of glucose transporters?
GLUT 1, GLUT 2, GLUT 3, GLUT 4
where is GLUT 1 found and describe its affinity:
GLUT 1 is found primarily in erythrocytes and other tissues with a high affinity (~ 1 mol/L)
where is GLUT 2 found and describe its affinity:
GLUT 2 is found in the liver and pancreatic B cells - these glucose carriers have the lowest affinity for glucose (~ 15mmol/L)
where is GLUT 3 found and describe its affinity:
GLUT 3 is found in the brain and other tissues, this glucose carrier has a high affinity for glucose (~1 mol/L)
where is GLUT 4 found and describe its affinity:
GLUT 4 is found in the muscles and adipose tissue and this glucose carrier has a low affinity of (~ 5mmol/L)
hexokinase is allosterically inhibited by high levels of ______, this is an important control step because:
it prevents over consumption of cellular ATP to form G-6-P when glucose is not limiting
what glucose concentrations are hepatocytes exposed to?
regularly exposed to relatively high glucose concentration via hepatic portal vein
what glucose carrier protein do hepatocytes express:
expresses GLUT 2 that has the highest Km that shows the lowest affinity to glucose
what do hepatocytes use instead of hexokinase for the phosphorylation of glucose and how do the Km values differ between the two enzymes?
- Expresses Glucokinase (GK) instead of Hexokinase (HK) for the phosphorylation of glucose
- GKs have higher Km than HK those show relatively low affinity to glucose
difference in inhibition between HK & GK:
Gk high Km; is activated by high blood glucose and insulin but NOT inhibited by G-6-P like Hk is
what does Gk allow for and why is it so crucial?
enzyme allows the liver to remove excess glucose for glycogen synthesis and minimise, after eating, hyperglycaemia
2 primary isoforms (isozymes) of pyruvate kinase and their locations:
- M-type: Muscle & Brain
- L-type: Liver
L-type pyruvate kinase is covalently phosphorylated when:
blood glucose is low
Phosphorylated L-type is less active compared to … which prevents:
those not phosphorylated
this prevents liver cells to consume glucose when there is a demand in other parts of the body
cori cycle:
in an oxygen deficit anaerobic respiration, muscle cells produce lactate. In the Cori cycle, lactate is released in the blood. In the liver conversion of lactate to pyruvate and to glucose takes place using 6 ATP by a process known as gluconeogenesis. Glucose is then released from liver cells back into the blood to be taken up by peripheral tissues.
summary of gluconeogenesis:
•Takes place primarily in the liver and kidney cells
•Essential for maintaining blood glucose concentration
•Major precursors are Glycerol, amino acids, and lactic acid
•Require specific enzymes (it is not a reverse of glycolysis)
The energy conserving phase of glycolysis generates:
2xNADH and 2xATP from glucose
Pyruvate kinase is a key regulatory step, modulated by:
hormones, ATP and fructose 1,6-bisphosphate
Pyruvate used to make ATP in anaerobic conditions generates:
lactate which is recycled in the liver using the Cori cycle
Pyruvate dehydrogenase is another key enzyme regulated by:
energy and acetyl CoA
glycolysis yields:
Yields 2 ATP (net total) molecules for every one glycose molecule digested down to pyruvate
➢Yields 2 NADH per every glucose digested by glycolysis
glycolysis takes place in:
the cytosol
glycolysis - ana/aerobic?
anaerobic
Hypoxia-inducible factor (HIF) regulated genes:
oxygen deprived, hypoxia is known to allow HIF transcription factor to turn on many enzymes of glycolysis
gluconeogenesis - 2 carboxylates to regenerate:
Phosphoenolpyruvate
gluconeogenesis - Glycerol as substrate to regenerate:
DHAP
4 key enzymes of gluconeogenesis:
hexokinase - Glucose
6-phosphatase
phosphofructokinase - Fructose
1,6-bisphosphatase
pyruvate kinase - Phosphoenol- pyruvate carboxylase & Pyruvate carboxylase
Warburg Effect:
tumours and other proliferating or developing cells, the rate of glucose uptake dramatically increases and lactate is produced, even in the presence of oxygen and fully functioning mitochondria
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