Lecture 22 WEB: Go to pollev.com/ucibio TEXT: Text UCIBIO to 37607 After joining session, text your question

Lecture 22 objectives Understand hormonal regulation of fatty acid mobilization Understand how fats provide energy to the brain Understand differences and similarities between starvation and diabetes Describe the reactions of fatty acid synthesis Compare FAS and b-oxidation Understand the regulation of fatty acid metabolism

Hormonal regulation

The brain problem… Most energy stored as fatty acids Brain only uses Glc Fatty acids  Glc?

The TCA

The brain problem… Most energy stored as fatty acids Brain only uses Glc Fatty acids  Glc? How does brain function during starvation?

Production of ketone bodies Starvation  Glycogen = 1 day Amino acids  Glc. BUT… Muscles can use fatty acids ( need for Glc) Gluconeogenesis OAA, so TCA Without , liver makes “___________” from fats

Ketone bodies

Diabetes & ketone bodies Starvation  __ KB  Used by brain Extreme starvation  Muscle breakdown No insulin  _ Blood sugar, AND _ FA breakdown Too much Acetyl CoA  __ Ketone bodies Brain has plenty of Glc! __ Ketone bodies in blood = __ pH  __ Death

If only…

Making fatty acids = adding 2 Cs to chain!

AcCoA  Malonyl CoA

ACP in FAS

FAS

FAS

Fatty acid synthesis

Substrate shuttling in FAS

Substrate shuttling in FAS

Further steps…

Further steps…

Data analysis Liraglutide is a drug that inhibits production of Glucagon. Treat normal and diabetic mice with Liraglutide and measure levels of blood glucose and ketone bodies. -Liraglutide +Liraglutide Glucagon levels Normal Diabetic -Liraglutide +Liraglutide Blood glucose Normal Diabetic -Liraglutide +Liraglutide Ketone bodies Normal Diabetic

Regulation of FAS & breakdown

Allosteric regulation of ACC