Metabolic Review - Skildum Flashcards
What are the four important metabolic states?
- Fed: Lasts 2-4 hours after a meal
- Fasted: Overnight without eating
- Starved: Prolonged fasting
- Hypercatabolic: Trauma, sepsis, etc.; not related to meals (can override any of the above metabolic states)
What accounts for the majority of the chemical energy in your body?
Triacylglycerol
What is the function of the GI System according to Dr. Skildum?
The GI system extracts chemical energy from food and makes it available for work in different tissues of the body, and at different times throughout the day.
-According to Skildum
What are the organ responses to feeding? What does the body want? How does it happen?
- Teleological statement (what the body wants):
- After eating, the body wants to store calories that exceed its immediate energy needs, so that it can withstand periods of nutrient unavailability. The body stores excess calories as carbohydrate, fat, and protein.
- Mechanistic statement (how it happens):
- After eating, nutrients stimulate the release of specific hormones, such as insulin, that upregulate biosynthetic pathways in different tissues.
Why is insulin important?
- Insulin is the most important hormone regulating storage pathways in the fed state.
- Insulin release from pancreatic beta cells is directly responsive to the concentration of glucose in the blood.
- Insulin inhibits the release of glucagon, the major regulator of catabolism in the fasted state.
How does the relative amount of carbohydrates in the meal determine the ratio of insulin to glucagon?
High carbs => More insulin
High protein => Less insulin, more glucagon
How does the insulin receptor work?
- Ligand-activated tyrosine kinase transmembrane signaling proteins:
- ligand (insulin) => binds to receptor
- structural changes occur within the receptor => autophosphorylation of various tyrosine residues
- structural changes => recruitment of specific adapter proteins such as the insulin receptor substrate proteins (IRS)
- more phosphorylation => increase in the high affinity glucose transporter (Glut4) molecules on the outer membrane of insulin-responsive tissues
- phosphorylation also => MAP-kinase cascade leading to Glycogen phosphorylase is dephosphorylated and inactive
- Glycogen synthase is dephosphorylated and active
What does the liver do in response to feeding?
- The liver is the primary organ responsible for maintaining glucose homeostasis.
- After eating a carbohydrate rich meal:
- biosynthetic pathways that produce glucose (glycogenolysis, gluconeogenesis) are inhibited
- metabolic pathways that store glucose (fatty acid biosynthesis, cholesterol biosynthesis, protein synthesis, glycogenogenesis) are activated.
- After eating a protein rich meal, elevated amino acids in the blood increase the secretion of glucagon by pancreatic alpha cells. In this case, excess amino acids are used by the liver for gluconeogenesis.
How does the brain respond to feeding?
Oxidizes glucose to CO2 to make ATP through oxidative phosphorylation.
How do the RBCs respond to feeding, fasting, prolonged fasting, etc.?
Ferments glucose to pyruvate; exports lactate.
***NO MATTER WHAT METABOLIC STATE!***
How do the White Adipose Cells respond to feeding?
Ferments glucose to glycerol 3-phosphate, the backbone for triacylglycerol synthesis.
How does muscle respond to feeding?
- Skeletal muscle:
- Glycolysis, fatty acid beta oxidation, glycogenogenesis, protein synthesis
- Cardiac muscle:
- Fatty acid beta oxidation (60-80%); Oxidation of glucose and lactate (20-40%).
How does the gut (cells of the gut) respond to feeding?
- Intestinal epithelial cells:
- Convert glutamine, glutamate and aspartate from the diet to a-ketoglutarate.
- In the fed state, gut epithelial cells use glutamine, aspartate and glutamate as their primary fuel.
- These amino acids come from the lumen of the gut, from dietary protein.
- Colonocytes:
- Use short chain fatty acids (acetate, butyrate, etc.) produced by gut bacteria.
What are the organ responses to fasting? What does the body want? How does it happen?
- Teleological statement (what the body wants):
- In between meals, the body wants to mobilize stored energy so that it can continue to perform work.
- Mechanistic statement (how it happens):
- Low carbohydrates in the blood promote the release of glucagon, a major regulator of hepatic fuel mobilization, from pancreatic alpha cells.
- Furthermore, intracellular enzymes that activate fuel mobilization pathways are directly regulated by energetic imbalance.
- e.g. AMP-K.
How does the Pancreas respond to fasting?
- Senses low blood glucose => Produce GLUCAGON
- The glucagon receptor is a seven transmembrane domain heterotrimeric G protein coupled receptor.
- Ligand binding causes activation of adenylate cyclase, production of cAMP, and activation of PKA.
