Glycolysis Flashcards
(19 cards)
What are the different GLUTs, and where are they/what do they do?
1- In RBCs.
2- Hepatocytes, beta cells of pancreas. Low affinity and high capacity to act s glucose sensor for global fasted/fed state.
3- Neurons. High affinity and insulin independent as bran can only use glucose for energy.
4- Myocytes and adipocytes. Insulin dependent as can use fatty acids for fuel too.
What occurs to pyruvate in the cytoplasm?
It is retrained here often in skeletal muscle during hypoxia. Pyruvate is converted to lactic acid by lactate dehydrogenase, also doing NADH–>NAD+ needed back in glycolysis.
Describe effectors of PFK-1.
High energy signals citrate and ATP allosterically inhibit it, while ADP, AMP, and F2,6BP (this can even overcome allosteric inhibition to push glycolysis forward continuously when needed).
Describe PFK-2.
It creates F2,6BP to allosterically activate PFK-1 when needed.
During fasting state the glucagon causes PFK-2 to be phosphorylated, leading to kinase domain inactivity and phosphatase domain activity (PFK-2 is inhibited overall). In fed state, PFK-2 is dephosphorylated, kinase is active, phosphatase is inactive, and F2,6BP is produced to override building citrate and ATP levels.
Describe pyruvate kinase.
Globally: Fasting signals (ex. Glucagon) cause PKA to activate, which phosphorylates and inactivates pyruvate kinase. Insulin activates phosphatases to do the opposite.
Tissue-wide/allosterically: ATP, acytyl CoA, long chain fatty acids, and alanine decrease PK activity, F1,6BP increases it.
Describe the NADH shuttle in most tissues.
Cytoplasm: Aspartate is converted to OAA, is converted to malate (also does NADH–>NAD+, can move into matrix via a-ketoglutarate transporter).
Matrix: Malate is converted to OAA (also NAD+–>NADH), is converted to aspartate (can move into cytoplasm via glutamate/aspartate transporter).
Describe the NADH shuttle found in skeletal muscle.
In cytosol: DHAP is converted to glycerol-3-phosphate (also converts NADH to NAD+).
In inter membrane space: At complex 2, glycerol-3-phosphate is converted back to DHAP (also converts FAD to FADH2).
Describe the penthouse phosphate pathway.
- It is the major source of NADPH
- Produces ribose-5-phosphate needed for pur/pyr synthesis
- Produces GAP that is used in TCA and ETC for energy harvest.
Rate limiting, regulated step is: NADP+–>NADPH via G6P-dehydrogenase (is upregulated by G6P presence).
Describe fructose metabolism.
Occurs in the liver primarily.
- Fructose is converted to fructose-1-phosphate via fructokinase (requires ATP).
- Fructose-1-phosphate is converted to glyceraldehyde or DHAP via F1P aldolase.
- Glyceraldehyde is converted to GAP via triose kinase, DHAP is converted to GAP via TIM.
Describe galactose metabolism.
Occurs in most tissues.
- Galactose is converted to galactose-1-phosphate via galactokniase (requires ATP).
- Galactose-1-phosphate is converted to glucose-1-phosphate via GALT (requires UDP-glucose conversion to UDP-galactose, which is then converted back to UDP-glucose via UDP-galactose isomerase).
- Glucose-1-phosphate is converted to G6P via phosphoglucomutase.
Where does gluconeogenesis occur?
In the liver primarily, somewhat in kidneys, when hepatic glycogen stores are depleted.
What is the first bypass step of gluconeogenesis?
Bypasses pyruvate kinase reaction via pyruvate carboxylase.
- Pyruvate carboxylase reacts with HCO3- (requires ATP), and then moves it onto pyruvate to create OAA.
- OAA is reduced to malate, which is moved from matrix into cytosol.
- Malate again becomes OAA, which then loses the CO2 and becomes phosphoenolpyruvate via GTP–>GDP reaction.
What is the second bypass step of gluconeogenesis?
Bypasses PFK-1 reaction via F1,6-biphosphatase.
The above enzyme changes F1,6-biphosphate to F6-biphosphate, thus releasing a Pi too.
AMP and F2,6-biphosphate downregulate this enzyme.
What is the third bypass step of gluconeogenesis?
Bypasses hexokinase reaction via action of ER-membrane bound glucose-6-phosphatase in the liver and kidney, which converts glucose-6-phosphate to glucose only when G6P levels rise.
Describe G6PD deficiency.
It is common in areas with malaria as it confers resistance in heterozygotes.
Leads to metheglobin (oxidized Hb) in RBCs and hemolytic anemia (glutathione is not maintained in reduced form, thus glutathione peroxidase system, the chief antioxidant defense, cannot function).
ROSs cannot be removed from the cell.
Describe essential fructosemia.
Fructokinase deficiency.
It is benign, and really just leads to increased fructose levels in urine.
Describe hereditary fructose intolerance.
Autosomal recessive.
Occurs after breast milk weaning as this does not have fructose.
Aldolase B absence, only it can cleave fructose-1-phosphate. Now F1P builds up, symptoms are vomiting, hypoglycemia, jaundice, acidosis, and coma.
Why does F1P buildup cause hereditary fructose intolerance?
It’s accumulation leads to a decrease in ATP and Pi levels.
- ATP decrease blocks gluconeogenesis.
- Pi decrease blocks glycogenolysis, prevents ADP phosphorylation (leads to 2ADP–>ATP+AMP, and AMP is then converted to urate), and increases AMP deaminase function (thus increased purine catabolism, resulting urate formation and hyperuricemia with gout).
Describe galactoremia.
GALT deficiency.
Common: Failure to thrive, liver damage, bleeding, sepsis
Severe: Neonate death, liver failure, retardation (can be avoided with restricted galactose diet in first 10 days).
Cataracts may form as accumulated galactose becomes galactitol, which can form cataracts.
Leads to galactose-1-phosphate trappage, which can lead to hyperuricemia.
