Flashcards in Skildum: Nutrition, Metabolism Review Deck (60):
What is the function of the GI system?
Extract CHEMICAL energy from food and make it available for WORK in different tissues of the body at different times throughout the day.
What is the most calorie dense fuel?
FA 9 kcal/gram
Glucose and AA are 4 kCal/gram
What are the 4 metabolic states?
1. Fed: lasts 2-4 hrs after a meal
2. Fasted: Overnight without eating
3. Starved: Prolonged fasting
4. Hypercatabolic: Trauma, Sepsis (not related to meals)
What does the body want after eating (teological statement)?
STORE calories that EXCEED its immediate energy needs so it can withstand periods of nutrient unavailability.
Calories are stored as carbohydrate, fat and protein.
How does the body respond after eating (mechanistic statement)?
Nutrients stimulate the release of specific hormones, like insulin, that regulate biosynthetic pathways in different tissues.
What is the most important hormone regulating storage pathways in the fed state?
Where is insulin released from and what does it respond to?
Insulin is released from PANCREATIC BETA CELLS in response to the conc of glucose in the blood.
What does insulin inhibit?
Glucagon--major regulator of CATABOLISM in the FASTED STATE
What determines the ratio of insulin to glucagon? How does that differ with a high carb and high protein meal?
Amt of carbs in the meal
High carbs--> more insulin
high protein--> less insulin and more glucagon
How do organs respond to feeding on a cellular level?
PP1 activation & GSK3 inactivation:
Glycogen phosphorylase is dephosphorylated and inactive;
Glycogen synthase is dephosphorylated and active
What organ is responsible for maintaining glucose homeostasis?
What happens in the liver in the fed state?
1. Pathways that PRODUCE glucose (glycogenolysis and gluconeogenesis) are INHIBITED
2. Pathways that STORE glucose are activated (FA/cholesterol/protein biosynthesis and glycogenogenesis)
What happens to AA after eating a protein rich meal?
AA are ELEVATED and increase the secretion of glucagon by PANCREATIC ALPHA CELLS
AA are used by the liver for gluconeogenesis
How does the brain respond to the fed state?
OXIDIZES glucose to CO2 to make ATP through oxidative phosphorylation
How do RBC respond to the fed state?
FERMENT glucose to pyruvate: exports lactate
How do white adipose cells respond to the fed state?
FERMENT glucose to glycerol 3 phosphate, the backbone for triacylglycerol synthesis
What is the difference between how skeletal and cardiac muscle respond to the fed state?
skeletal: Glycolysis, FA beta oxidation, glycogenogenesis, protein synthesis
Cardiac: FA beta oxidation (60-80%), Oxidation of glucose/lactate (20-40%)
What do intestinal epithelial cells do in response to the fed state?
Convert glutamine, glutamate and aspartate from the diet to a-ketoglutarate
What do colonocytes do in respond to the fed state?
Use short chain fatty acids produced by gut bacteria
What do epithelial cells use as their primary fuel in the fed state? Where do these AA come from?
Glutamine, aspartate and glutamate
Lumen of the gut from dietary protein
Is glucose completely oxidized by gut epithelial cells?
Note glucose is fermented to pyruvate, which is used as nitrogen acceptor to make alanine
What does the body want in the fasting state?
wants to mobilize stored energy so that it can continue to perform work
How does the body mobilize energy in the fasting state?
LOW CARBs 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.
Describe the glucagon receptor:
seven transmembrane domain heterotrimeric GPCR
What does a ligand binding to the glucagon receptor cause?
Activating of AC, production of cAMP and activation of PKA
What affect does PKA activation in the hepatocyte have on glycogen synthase, glycogen phosphorylase kinase and glycogen phosphorylase?
Glycogen synthase is phosphorylated and inactive.
Glycogen phosphorylase kinase is phosphorylated and active.
Glycogen phosphorylase is phosphorylated and active.
What is the REE?
approximately equivalent to the basal metabolic rate (BMR), is measured in the FASTED STATE
What does the liver do in response to fasting?
Increases production and export of glucose for use by other tissues
What are the two means by which the liver can increase production of glucose?
GLYCOGENOLYSIS uses hepatic glycogen stores.
GLUCONEOGENESIS uses carbon skeletons from amino acids, lactate, and glycerol to produce glucose. (Energetically expensive)
Where does the ATP to power gluconeogenesis come from?
FAD2H and NADH reduced by FA beta oxidation to ATP
What is a substrate for ketone body synthesis in the fasting state?
Acetyl co A produced by FA beta oxidation
How does skeletal muscle and respond to the fasting state?
Proteolysis (cortisol) 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.
How does cardiac muscle respond to the fasted state?
Increase in FA beta oxidation and a decrease in glycolysis to preserve glucose for other tissues
What can skeletal muscle use for energy in a prolonged fast? HOw does this differ from starvation?
If a prolonged fast progresses to starvation the skeletal muscle SHUTS OFF ketone bodies and runs off FA
How do the gut epithelial cells respond to the fasted state?
Still use GLUTAMINE as their primary fuel but it comes from the BLOOD not the lumen of the gut
How does adipose tissue respond to fasting?
Lipolysis of TAG:
--> FA (used as fuel by heart and liver)
--> glycerol (used for gluconeogenesis by the liver)
What does THE body want in the starvation state?
During famine, the body PRESERVE BODY STRUCTURE by degrading only tissue with the most caloric density FAT to provide energy.
How does the body preserve body structure and still provide energy in the starvation state?
Adipose TAG is mobilized for fuel and to synthesize KETONE BODIES.
Muscle protein breakdown is minimized.
Glucose is spared for red blood cells.
How does adipose respond to starvation?
Lipolysis of TAG increases
How does the liver respond to starvation?
It increases production of KB
Decreases gluconeogenesis (doesn't have pool of AA d/t decreased muscle breakdown)
How does skeletal muscle respond to starvation?
KB utilization decreases--> FA utilization increases
Muscle breakdown DECREASES--> decreases the pool of AA
How does cardiac muscle respond to starvation?
Continues to use FA (doesn't like KB)
What happens to glucose, KB and FA during starvation?
Small drop in glucose
Small increase in FA
Large increase in KBs
What will happen to urea cycle activity during an overnight fast? During starvation?
Increase in the urea cycle b/c metabolism is dominated by AA metabolism.
Over time you switch to FA metabolism which doesn't have N in it.
What is hypercatabolism?
The rapid mobilization of stored fuels to provide energy for wound repair and immune system function.
What causes hypercatabolism
What characterizes hypercatabolism?
sustained muscle and organ protein breakdown
How do the hormones that medaite hypercatabolism act?
Catecholamines peak than rapidly decline
Glucagon peaks and sustains
Cortisol is the last one activated put is sustained the longest
What does epi do?
Activates hormone sensitive lipase>
FA mobilized from adipose
What does cortisol do?
Activates MUSCLE proteolysis>
AA mobilized from muscle
What does glucagon do?
Activates HEPATIC glycogenolysis and gluconeogenesis
What is a nutrition goal for all recovering pts?
Maintain positive N balance
What is the eqtn for N balance?
N intake= (urinary urea N + 2)
What do gut epithelial cells, lymphocytes and cancer cells have in common?
they've all adapted to use AA glutamine as a fuel source b/c they all divide rapidly and need to get energy rapidly while preserving glucose.
Where is creatine synthesized?
Kidney and liver
What does creatine do?
Serves as a BUFFER of high energy phosphate bonds to replenish ATP in skeletal muscle, cardiac muscle, brain
What happens to the breakdown product of creatinine?
NOT metabolized and is excreted in the urine (constant and proportional to mass)
What is the CHI?
Measure of nutritional status
Urine creatinine is measured over 24 hours and compared with values obtained from healthy, well nourished subjects.
What physical signs are indicative of malnutrition?
Muscle mass in fingers, face
Body mass index (BMI)