carbs metabolism block 8 Flashcards
(39 cards)
What is the Fed state of metabolism?
A 2-4 hour period after a meal characterized by an increase in plasma glucose and amino acids due to food intake, with insulin released from the pancreas and fuel stores created, e.g., glucose stored as glycogen.
What is the fasted state?
Begins if no further fuel is ingested after the fed state, leading to a fall in plasma levels of glucose and amino acids, a decrease in insulin secretion, and an increase in glucagon release, initiating degradation of fuel stores.
What is insulin?
Synthesized in pancreatic beta-cells, insulin is the hormone of the fed state with anabolic actions, signaling through tyrosine kinase receptors.
What is glucagon?
Synthesized in pancreatic alpha-cells, glucagon is the hormone of the fasted state with catabolic actions, signaling through G protein-coupled receptors.
How is insulin released?
Insulin is released in a 2-phase process: 1. Release from granules (pre-made insulin), 2. Synthesis of new insulin.
How is insulin post-translationally modified?
Insulin starts as a bigger molecule called preproinsulin
It’s made in the ribosome on the rough ER
The “pre-” part is a signal sequence that tells the cell to move the protein into the endoplasmic reticulum (ER)
Signal sequence is removed → now it’s proinsulin
Inside the ER, the signal sequence is cleaved off and mature insulin is formed
What is the insulin signaling pathway?-CHEAT SHEET. just know what it activates
Insulin binds to its receptor, activating IRS-1, which activates PI3K, converting PIP₂ to PIP₃. PIP₃ activates PDK1, leading to Akt activation, resulting in glucose uptake, glycogen storage, and inhibition of glucose production in the liver.
What is the glucagon signaling pathway?-CHEET SHEET. Just know what it activates
Glucagon binds to its receptor, activating a G-protein that exchanges GDP for GTP. The GTP-bound α-subunit activates adenylate cyclase, converting ATP to cAMP, which activates PKA, leading to glycogen breakdown, inhibition of glycogen synthesis, and stimulation of gluconeogenesis.
How are dietary carbohydrates processed?
Dietary carbohydrates are digested in the mouth and gut, breaking glycosidic bonds to produce monosaccharides, which are absorbed via glucose transporters (GLUT) since monosaccharides cannot diffuse across cell membranes.
How does insulin enhance glucose transport?
Insulin promotes the movement of GLUT4 transporters from intracellular locations to the cell membrane in liver and muscle cells, increasing glucose uptake for storage.
This process occurs when activation of the insulin signaling pathway leads to Akt activation, which then phosphorylates GLUT4-containing vesicles, promoting their movement to the cell membrane.
What is the summary of glycolysis?
Glycolysis has two phases: 1. Preparation phase (traps glucose, forms 3C molecules, consumes 2 ATP), 2. Payoff phase (harvests energy, produces 4 ATP, 2 NADH, and 2 pyruvate).
What are the key steps of glycolysis?
Key steps include hexokinase (phosphorylates glucose), phosphofructokinase-1 (phosphorylates fructose-6-phosphate), and pyruvate kinase (substrate-level phosphorylation).
What is hexokinase’s role in glycolysis?
Hexokinase is the enzyme that catalyzes the first step of glycolysis. It uses ATP to add a phosphate group to glucose, forming glucose-6-phosphate. This reaction is irreversible and helps trap glucose inside the cell. Hexokinase also changes shape (induced fit) when it binds glucose, which helps prevent ATP from being wasted. via hydrolysis
How is glycolysis regulated by different types of hexokinase?
Hexokinase I–III are found in most tissues and are active at low glucose levels. They are inhibited by their product, glucose-6-phosphate (G6P). Hexokinase IV (glucokinase), found in the liver and pancreas, is active at high glucose levels and is regulated by glucokinase regulatory protein (GKRP), which controls its location in the cell.
How does glucokinase regulatory protein (GKRP) regulate glycolysis in the liver?
In the liver, GKRP controls the activity of glucokinase by changing its location. When glucose is low (fasted state), GKRP binds glucokinase and holds it in the nucleus, stopping glycolysis. When glucose is high (fed state), glucokinase is released into the cytoplasm, where it helps start glycolysis.
How is hexokinase (HK) activity regulated in glycolysis?
Hexokinase I–III are inhibited by their product, glucose-6-phosphate (G6P), in a process called feedback inhibition. In addition, insulin increases the production (transcription) of hexokinase enzymes, especially in the fed state.
What is the main regalatory enzyme in glycolysis?
Phosphofructokinase-1 (PFK-1) is the main regulatory enzyme with multiple regulation methods.
How is phosphofructokinase-1 regulated via ATP?
PFK-1 is an allosteric enzyme. High ATP levels inhibit it, slowing glycolysis, while low ATP levels and AMP activate it, promoting glycolysis.
How does regulation of phosphofructokinase-1 via ATP occur?
ATP acts as an inhibitor, favoring the T state of PFK-1, while AMP acts as an activator, shifting PFK-1 to the R state, promoting glycolysis.
How does insulin stimulate glucose uptake in adipose and skeletal muscle but not in the liver?
In adipose tissue and skeletal muscle, insulin stimulates the movement of GLUT4 transporters to the cell surface, increasing glucose uptake. In the liver, glucose uptake occurs through GLUT2 transporters, which are always present on the membrane and are not regulated by insulin.
What is the role of Fructose 2,6-bisphosphate (F26BP) in glycolysis regulation?-CHEAT SHEET
F26BP acts as an allosteric regulator in the liver, stabilizing the R-state of phosphofructokinase and increasing its activity.
How does phosphofructokinase-2 (PFK-2) work?
PFK-2 is a bi-functional enzyme with kinase and phosphatase domains, controlling the concentration of F26BP in the liver.
How is phosphofructokinase-2 regulated?-CHEET SHEET
When dephosphorylated, PFK-2 acts as a kinase, increasing glycolysis. When phosphorylated, it acts as a phosphatase, increasing gluconeogenesis.
What is the summary of the regulation of PFK-1?- JUST READ BRO
PFK-1 is regulated by allosteric modulators, phosphorylation/dephosphorylation mediated by insulin and glucagon, and transcriptional regulation by insulin.
