Lecture #32: Metabolism: Organ specialization

Read: pg. 590-593 (Section 19.5) AND pg. 664-672

HW: pg. 692 (Study Exercises 1,2,3,4)

Study Exercises:

1. Summarize the major features of fuel metabolism in brain, muscle, adipose tissue and liver

	Brain	Muscle	Adipose	Liver
Major Fuel(s) at Rest Or, function	Glucose	Glucose, fatty acids, ketone bodies Cardiac muscle prefers fatty acids at rest	Main function of adipocytes is to synthesize and store triglycerides.	Glucose and fatty acids. Liver can not use ketone bodies as fuel. Liver maintains levels of circulating fuels Liver can synthesize or degrade fatty acids, glucose and amino acids.
Preferred Fuel when Active	Glucose	Glucose (from glycogen) ATP buffer: Phosphocreatine Quick ATP: Glycolysis (glucose ® lactate) Cardiac muscle: Increases glucose consumption during heavy work.	Fatty Acids?	Fatty Acids
Alternative Fuel when Starving	Ketone Bodies	Fatty acids and ketone bodies	Fatty Acids?	Fatty Acids (Liver exports ketone bodies as fuel for other tissues)
Organ/Enzyme Specificity	Little gluconeogenesis and glycogen synthesis. But see: Hevor, 1994; Hevor and Delorme, 1991; Schmoll et al., 1995a; Schmoll et al., 1995b	Muscle synthesizes glycogen for its own use. (majority of glycogen is found in muscle). Muscle does not export glucose to other tissues because it lacks glucose-6-phosphatase. (Glycogen ® G6P G6P is not converted to glucose)	Adipocytes have enzymes for fatty acid oxidation and synthesis.	Liver buffers blood sugar by taking up glucose in response to hormones and blood [glucose]. Glucokinase traps glucose as G6P. Glucokinase activity varies with [glucose]

 

2. High Km of glucokinase is important for the role of the liver in buffering blood glucose because glucokinase is not saturated within physiological range of glucose concentrations. Consequently glucokinase activity increases in proportion with [glucose]. Phosphorylation of glucose via glucokinase traps glucose as G6P inside hepatocytes.
3. a. The Cori cycle operates during times of vigorous anaerobic exercise. Lactate that builds up during anaerobic glycolysis is transported from muscle (which lacks gluconeogenic enzymes) to liver. In the liver lactate is used to make glucose via gluconeogenesis. Glucose produced in liver is transported back to the muscle for immediate use or storage as glycogen.

3. b. The glucose-alanine cycle operates to remove ammonia from muscle and deliver it to the liver where it can be converted to urea for excretion. (The urea cycle operates only in the liver). The cycle would be active during periods of high amino acid metabolism. Amino acids are metabolized to make glucose during periods of starvation or glycogen depletion.
4. Why do different tissues contain different members of the GLUT family of glucose transporters?

Different tissues express different GLUT transporters because tissues have different physiological roles. Muscle takes up glucose after a meal for storage as glycogen. Adipocytes take up glucose after a meal because glucose provides a supply of glycerol-3-phosphate which is used to synthesize the glycerol backbone of triglycerides. GLUT 2 occurs primarily in liver and pancreatic beta cells. Its high Km for glucose (~60mM) means that it will not be saturated at physiological concentrations of glucose. Because it is not saturated glucose transport varies in proportion with glucose concentration. GLUT 1 and 3 are expressed in brain. Transport of glucose into brain is the limiting step in brain glucose utilization. Hypoxia tolerance may be associated with increased expression of GLUT 1 (Duelli et al., 2000). Why would increased glucose transport into brain increase tolerance to low oxygen?