Lecture 3 Feeder Pathways for Glycolysis and Gluconeogenesis Flashcards
What glucose transporters are most significant?
- GLUT 1 → ubiquitous → basal glucose uptake
- GLUT 2 → liver, pancreatic islets, intestine → in liver, removal of excess glucose from blood; in pancreas, regulation of insulting release
- GLUT 4 → Muscle, fat, heart → Activity increased by insulin
When do GLUT transporters open?
Transporters only open when glucose is at the indicated Kt concentration
- Lower Kt = higher affinity for glucose
- Higher Kt = lower affinity for glucose
Kt of GLUTS 1, 2, and 4
- GLUT 1 → Kt = 1.5 mM
- GLUT 2 → Kt = 66 mM
- GLUT 4 → Kt = 5 mM
How does fructose feed into glycolysis in the muscle vs. the liver?
- Muscle → fructose is phosphorylated to F6P by hexokinase, which has low specificity for hexoses (phosphorylates glucose and fructose alike).
- Liver → fructose is phosphorylated to F1P by fructokinase. F1P is cleaved to trioses and enters glycolysis as 2 molecules of glyceraldehyde 3- phosphate (GAP). This bypasses the PFK-1 reaction.
What is the consequence of fructose bypassing PFK-1 reaction in the liver?
can lead to the unregulated production of lactic acid and lactic acidosis if large amounts of fructose are consumed.
- fructose will be oxidized all the way to pyruvate and downstream to citrate which can bind to PFK-1 to inhibit it but this does not effect the fructose feeder pathway
Fructose and fat synthesis
Fructose is also rapidly metabolized to DHAP, pyruvate and acetyl-CoA, precursors for fat synthesis. This gives rise to elevated blood triglyceride levels after feeding on fructose and sucrose. This is potentially relevant for the pathogenesis of atherosclerosis – a disease of vascular lesions leading to plaques that can rupture into pieces which can block small arteries, resulting in heart attacks, strokes, renal failure.
Other feeder pathways for glycolysis
disaccharides can also be fed into but they are first broken down into there monosaccharides
Common feeder pathways for gluconeogenesis
Has non-carbohydrate precursors
- pyruvate
- Lactate
- Amino acids
- Glycerol
Lactate as a substrate of gluconeogenesis
Via Cori Cycle
Lactate can be a gluconeogenic substrate when it is converted to pyruvate in the liver. It is generated in large quantities by the muscles during exercise. Lactate is exported from muscle, taken up by the liver, converted to glucose and released back to muscle through the bloodstream.
Amino acids as substrates of gluconeogenesis
All amino acids (synthesis or dietary) except leucine and lysine can be glucogenic; they can be converted to pyruvate or to a citric acid cycle intermediate. During fasting, muscle protein breakdown is an important source of glucose.
Glycerol as a substrate of gluconeogenesis
Glycerol from triacylglycerol can be glucogenic after it is converted to DHAP by any of various pathways such as conversion to glycerol-3-phosphate (e.g., by glycerol kinase) to DHAP, (e.g., by glycerol-3-phosphate dehydrogenase) which is a common intermediate in both glycolysis and gluconeogenesis.
