Starvation/Diabetes

PHASES OF FASTING
 Problem: normally brain uses only glucose for fuel, not fat
 Solutions:
o Increased:
 Glycogenolysis from liver glycogen
 Supplies blood glucose
 Gluconeogenesis
 Ketogenesis (brain can use ketone bodies if their serum concentration
increases sufficiently
o Theses phases overlap
 Terminal phase
o Organism can’t keep up with all demands and organs begin to fail
 Thus, need coordination of numerous biochemical pathways in various organs

~ SOURCES OF BLOOD GLUCOSE DURING STARVATION

 Ingested glucose, liver glycogen, gluconeogenesis

~ BLOOD PROFILES DURING STARVATION

 Glucose, ketone bodies, free fatty acids, insulin, glucagon
MAXIMUM PHASE OF GLUCONEOGENESIS: ENERGY AND SUBSTRATES
 Energy source: oxidation of fat (but not in the brain)
 Carbon sources for gluconeogenesis (mainly for the brain):
o Glucogenic amino acids (from skeletal-muscle proteins)
o Glycerol (from triglycerides = fats)
 Problem: will run out of carbon sources for gluconeogenesis (mainly for the brain) long
before 50 days are up
o Will be “solved” by making ketone bodies alternate fuel for the brain

SYNTHESIS OF KETONE BODIES (KETOGENESIS): LIVER AND KIDNEY

 Acetoacetate and beta-hydroxybutyrate both have 4 carbons

o Only diff is one has a ketone, and one has a reduced alcohol
 Acetone is decarboxylation product of acetoacetate
 Ketone bodies are produced only in liver and kidney
 Acetyl CoA is the precursor
o TAKES 3 TO MAKE ACETOACETATE
 HMG CoA is a precursor of steroids and other compounds
 Ketones are a soluble, transportable form of acetyl CoA

FUEL SOURCES USED BY BRAIN

TERMINAL PHASES OF FASTING

 Protein-wasting leads to impaired:
o