carbs metabolism block 8 Flashcards
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 is synthesized as preproinsulin, which contains a signaling sequence and pro-peptides that are not part of the mature insulin.
What is the insulin signaling pathway?
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?
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 adipocytes and muscle cells, increasing glucose uptake for storage.
How does insulin enhance glucose transport occur?
Activation of the insulin signaling pathway leads to Akt activation, which 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 uses ATP hydrolysis, is irreversible, and undergoes induced fit upon substrate binding to prevent water from hydrolyzing ADP.
How is glycolysis regulated via hexokinase?
There are four types of hexokinases. HK I-III are active at low glucose concentrations, while HK IV (glucokinase) is active at high glucose concentrations in the liver.
How is glycolysis regulated via glucokinase regulatory protein (GKRP)?
In the liver, GKRP binds glucokinase under normal conditions. In the fed state, high glucose levels release glucokinase into the cytoplasm. Low glucose levels transport glucokinase back to the nucleus, reducing glycolysis.
What are other types of regulation of glycolysis via hexokinase?
Feedback inhibition occurs in HK I-III by G6P, and transcriptional regulation is upregulated by insulin.
What is the main point of regulation of 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?
Insulin promotes GLUT4 translocation in adipose and skeletal muscle, while GLUT2 in the liver is not affected by insulin.
What is the role of Fructose 2,6-bisphosphate (F26BP) in glycolysis regulation?
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?
When dephosphorylated, PFK-2 acts as a kinase, increasing glycolysis. When phosphorylated, it acts as a phosphatase, increasing gluconeogenesis.
