Biochemistry-Integration Flashcards
You eat a subway sandwich with bread, meat and mayo. Where do the nutrients from your sandwich go after they are absorbed by the intestine?
Glucose from the bread and amino acids from the meat go straight to the liver. Fat from the mayo gets packaged into chylomicrons and goes to the lymph, to the thoracic duct, into the general circulation and on to adipose tissue.
What happens when glucose enters the pancreas and binds to the beta cells?
Insulin levels go up. Insulin inhibits glucagon secretion, so the ratio of insulin to glucagon goes way up.
What metabolic pathway is active in every tissue when blood glucose is high?
Glycolysis. The pathway is turned on by insulin.
Aside from glycolysis, what other pathway is turned on by insulin in the liver?
Glycogen synthesis. Insulin turns on protein phosphatase which takes the phosphate off of glycogen synthase and makes it active (shown below). Note that once this store becomes saturated glucose is converted to fat by the de novo fat synthesis pathway.
Once you load up your glycogen storage and start synthesizing new fat de novo, what does the liver do with the new fat?
Packages triglycerides as VLDL and sends it to adipose tissue, where it meets lipoprotein lipase.
If glucose and oxygen go into the brain, what comes out?
CO2 and H2O. The brain uses glucose for ATP.
Why do RBCs need glucose?
They do not have mitochondria and rely solely upon glucose for energy.
What transporters are stimulated by insulin in fat and muscle when blood sugar levels are high?
GLUT 4 transporters. This allows for facilitated diffusion of glucose.
What organ plays a large role in bringing blood glucose levels down?
Muscle. When blood glucose levels are high, it will use glucose as its primary fuel. It will also build up its glycogen stores (carb loading).
How does insulin help us rebuild and renew our bodies?
Muscle protein is slowed down and global protein synthesis is stimulated by insulin.
How does insulin promote fat growth?
It promotes expression of LPL at the face of adipose tissues. This allows for chylomicron and VLDL triglyceride core degradation, fatty acids diffuse into adipose tissue, glycerol goes to the liver, insulin stimulates glucose entry, glucose goes to DHAP -> glycerol-3-P and then fatty acids are added on to form triacyglycerides for storage.
How does the pancreas react to decreasing blood glucose levels?
Alpha cells release glucagon.
What organs have glucagon receptors?
Liver and adipose tissue…not on muscle!
How does glucagon help increase blood glucose levels so you don’t pass out?
Glucagon activates PKA -> PKA activates phosphorylase kinase -> phosphorylase kinase activates phosphorylase -> glucose-1-P is cleaved from glycogen -> glucose-1-P is converted to glucose-6-P, then to glucose and leaves in the blood
What is the next source of fuel in the fasted state as glucose levels fall?
Glucagon binds to receptors of adipose tissue. This activates protein kinase which activates hormone sensitive lipase. Hormone sensitive lipase hydrolyzes triglycerides to fatty acids and glycerol, which are released into the blood. The fatty acids bind to serum albumin and are delivered to all tissues that can use them. Fat-using tissues switch off glycolysis and turn on beta-oxidation for energy in the fasted state.
Why is the liver crucial in protecting us from free fatty acid damage during the fasted state?
Triglyceride hydrolysis goes overboard and releases tons of FFAs. The liver mops up the extra to protect us from damage.
Why can the liver make ketone bodies?
It gets plenty of energy and often does not need the excess acetyl CoA. The liver can combine these to form ketone bodies and release them into the blood for use by other tissues.
What is the key ingredient for gluconeogenesis during an overnight fast?
Insulin levels are low so muscle protein tends to breakdown into amino acids. Ala is released and goes to the liver. Ala undergoes transamination to pyruvate in the mitochondria. Pyruvate carboxylase makes OAA from pyruvate. OAA leaves the mitochondria as aspartate/malate and it is converted back to OAA in the cytosol. PEPCK takes OAA to PEP. The next bypass reaction is Fru-1,6-bisphosphatase popping off Fru-1,6-BP’s phosphate to form Fru-6-P. The final bypass step is gluc-6-phosphatase popping off gluc-6-P’s phosphate to form glucose.
When does glucokinase take glucose out of the blood?
When levels are very high, this happens because the enzyme has a high Km.
Activators of PFK-1? Inhibitors of PFK-1?
Activators: Fru-2,6-BP (main activator in liver) and AMP. Inhibitors: ATP and Citrate.
Activation of pyruvate kinase? Inhibition of pyruvate kinase?
Activator: Fru-1,6-BP and dephosphorylation by insulin. Inhibitor: Ala and phosphorylation by glucagon.
What are feedback inhibitors of pyruvate dehydrogenase complex?
NADH and Acetyl CoA
What happens to cytoplasmic citrate during de novo fatty acid biosynthesis?
Citrate lyase breaks it up into oxaloacetate and acetyl CoA. Acetyl CoA is converted to Malonyl CoA by acetyl CoA carboxylase.
What de novo fatty acid synthesis enzyme is induced during the well fed state? What activates this enzyme? What inhibits it?
Acetyl CoA carboxylase. Activates: citrate and insulin. Inhibits: Feedback palmitoyl CoA and Glucagon and activation of AMP-activated protein kinase
What compound ensures that fatty acid synthesis and beta oxidation do not form a futile cycle?
Malonyl CoA blocks the uptake of fatty acyl CoA into the mitochondrial matrix by inhibiting the enzyme CPTI.
What stimulates glycogen breakdown in muscle during exercise?
Ca2+ (binds calmodulin and activates phosphorylase kinase which can activate glycogen phosphorylase), AMP (allosterically activates glycogen phosphorylase) and EPI (also activates phosphorylase kinase which can activate glycogen phosphorylase). Note that GLUT 4 transporters are also stimulated by exercise (AMP) in addition to insulin. Glycolysis is also stimulated by exercise (AMP) by activation of PFK-1
Summarize the effects of insulin, glucagon and epinephrine in each of the processes listed below
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A 10 year old girl presents with frequent urination and thirst. Despite increased appetite she complains of 10 pound weight loss. Labs reveal hyperglycemia, ketoacidosis, high levels of fatty acids, and hypertriglyceridemia. Why is she presenting this way?
Absence of insulin in a type-1 diabetic = too much glucagon secretion. This results in too much gluconeogenesis -> high blood sugar, lack of LPL expression -> high blood sugar, hormone sensitive lipase activation -> excess fatty acid release -> liver mops it up and sends it out as VLDL (hypertriglyceridemia) and ketone bodies -> overproduction of ketone bodies and ketoacidosis -> metabolic acidosis -> coma, lack of GLUT 4 expression -> high blood sugar, protein breakdown -> muscle wasting and increased gluconeogenesis precursors,
