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.
How does the liver respond to fasting?
- The liver increases production and export of glucose for use by other tissues.
- Glycogenolysis uses hepatic glycogen stores.
- Gluconeogenesis uses carbon skeletons from amino acids, lactate, and glycerol to produce glucose.
- The ATP to power gluconeogenesis comes from the FAD(2H) and NADH reduced by fatty acid beta oxidation.
- The acetyl CoA produced by fatty acid beta oxidation is a substrate for ketone body synthesis.
How does Muscle respond to fasting?
- Skeletal muscle:
- Proteolysis produces free amino acids.
- Branched chain amino acids are used by the muscle as fuel.
- Alanine and glutamine are exported for use as gluconeogenic substrates by the liver.
- As the fast prolongs, skeletal muscle can use ketone bodies for energy.
- Cardiac muscle:
- Fatty acid beta oxidation increases; glycolysis decreases.
How do White Adipose Cells respond to fasting?
Lipolysis of triacylglycerol produces fatty acids (used as fuel by heart, liver) and glycerol (used for gluconeogenesis by liver).
How do Gut Cells respond to fasting?
- Gut epithelial cells still use glutamine as their primary fuel in the fasted state
- ***but it comes from the blood, not the lumen of the gut.
How does the Brain respond to fasting?
- Fatty acids broken down into Ketone Bodies by the liver to supply energy to the brain.
What are the organ responses to prolonged fasting/starvation? What does the body want? How does it happen?
- Teleological statement (what the body wants):
- During famine, the body preserves body structure by degrading only tissue with the most caloric density (fat) to provide energy.
- Mechanistic statement (how it happens):
- Adipose triacylglycerol is mobilized for fuel and to synthesize ketone bodies;
- muscle protein breakdown is minimized;
- glucose is spared for red blood cells.
What are the major metabolic changes that occur with prolonged fasting/starvation?
- Lipolysis of adipose triacylglycerol increases
- The liver increases its production of ketone bodies.
- Ketone body utilization by skeletal muscle decreases
- Ketone body utilization by the brain increases
- Cardiac muscle continues to use fatty acids; the heart does not like to use ketone bodies.
- Skeletal muscle breakdown decreases; the liver decreases gluconeogenesis.
What will happen to urea cycle activity during prolonged fasting?
- Increased initially - relying heavily on amino acid metabolism => excess nitrogen
- Prolonged starvation decreases - living primarily off of fatty acids => no nitrogen to be excreted through urea cycle
What is hypercatabolism?
- Rapid mobilization of stored fuels to provide energy for wound repair and immune system function.
- It can occur after surgery, trauma, burns, or sepsis.
- Hypercatabolism is characterized by sustained muscle and organ protein breakdown.
- ***Sustained protein breakdown and amino acid catabolism.
What are the two phases of hypercatabolism?
- Ebb Phase
- Flow Phase
What happens during the Ebb Phase of hypercatabolism?
- epinephrine activates hormone sensitive lipase => fatty acids moblized from adipose
- cortisol activates muscle proteolysis => amino acids mobilized from muscle
- glucagon activates hepatic glycogenolysis and gluconeogenesis
Catecholamines/Epinephrine release during hypercatabolism causes what?
- Increase Renin release
- Increase Lipolysis
- Stop Insulin release
- Increase Glucagon release
Glucagon release during hypercatabolism causes what?
- Hyperglycemia
- Proteolysis
Glucocorticoid release during hypercatabolism causes what?
- Proteolysis
- Gluconeogenesis
- Lipolysis
A 43 year old male is 5’10” tall and weighs 170 pounds and doesn’t exercise. He wants to maintain a healthy weight without changing his level of physical activity. About how much would you recommend he eat each day?
about 2,159 kcal/day
Which molecule is the least oxidized?
- A. alanine
- B. fructose
- C. glucose
- D. oleate
- E. stearate
E. stearate is fully unsaturated– it has highest ratio of carbon to non-carbon
A 28 year old research subject weighed 77 kg and was 173 cm tall. In the fasted state, while mentally and physically relaxed, he consumed 15.7 L of oxygen per hour and expired 12.0 L of carbon dioxide. What is his RQ?
RQ = (12.0 L) / (15.7 L) = 0.7643
A male patient presented with a BMI of 33 kg/m2 and a waist circumference of 47 inches. What dietary therapy would you consider most helpful?
- A. Decreased intake of total calories
- B. The same amount of total calories, but substitution of carbohydrates for fat
- C. Increased intake of total calories
- D. The same amount of total calories, but substitution of protein for fat
- E. The ice cream and sherry diet
A. Decreased intake of total calories
At non-protein RQs above 0.85, the primary fuel for respiration is. . .
- A. carbohydrates
- B. protein
- C. fat
A. carbohydrates
When a person is burning fat for the majority of his energy, his RQ will be lower than if he were using mostly carbohydrates. This is because fat is more. . .
- A. Oxidized
- B. Reduced
- C. Delicious
B. Reduced
A healthy woman ate a meal of mixed carbohydrates, fat and protein on monday evening, then had her respiratory quotient (RQ) measured by indirect calorimetry. She did not eat anything for three days, and had her RQ measured again on Thursday. What happened to her RQ from Monday to Thursday?
- A. Decreased
- B. Stayed the same
- C. Increased
A. Decreased - because she is switching from oxidizing carbs in the fed state to oxidizing fat in the starved state.
