• phosphorylate enzyme that produces F2,6P, so it is INACTIVE
• inactivate glycogen synthase (phosphorylation)
• activate GPK, which activates glygoen phosphorylase
  • cleave glucose from non-reducing end of glycogen

1. glycogen cleave off G1P from non reducing end via glycogen phosphorylase
2. G16 converted to G6P via phosphoglucomutase
3. G6P enters ER
4. G6P goes to glucose and inorganic phosphate via G-6 phosphatase
5. glucose and phosphate go back into cytosol
6. glucose leave cell via GLUT2

• PEP carboxykinase
• fructose 1,6 biphosphatase
• glucose 6 phosphatase

alanine

ATP content

methionine

threonine

Ala

Ser (made from Gly)

Cys

• react Glu with GDH to form NH3 and alpha KG
• convert OAA to Aspartate via AST alpha KG dependent mechanism

In order to make urea, we need a NH3 and aspartate

1. leads to NET proteolysis of proteins, producing AA's
   1. some AA are released into the blood
   2. other AA are converted to alpha keto acids via aminotransferase
   3. produces energy
2. glycogen breakdown occurs
   1. yields G6P
   2. G6P can undergo glycolysis and make two pyruvates
   3. produces energy
3. because of NH3 being on Glu from AT reaction, via ALT, we can take 2 pyruvates to two Ala
4. Ala released into blood
   1. produces energy

1. activates PKA
2. phosphorylation of hormone sensitive lipase and perilipins
   1. lipase phosphorylation catalyzes hydrolysis of TAG's
      1. yields FA and glycerol
      2. free fatty acid go into blood  and bind to albumin, and is carried to the liver (heart, muscle, and liver can pick it up and use it as a source of energy)
      3. glycerol go into the blood and to the liver
   2. perillipins undergo confirmation change to expose lipid surface of droplet so lipase can remove TAG from lipid droplet

1. glycogen via glycogeneolysis
2. OAA via gluconeogenesis

1. add a CoA to it
2. use fatty acyl CoA carnitine transferase system
3. undergo beta oxidation
4. produces acetyl CoA

1. two acetyl CoA's produce acetoacetyl-CoA via thiolase
2. acetoacetyl CoA and acetyl CoA produce HMG-CoA via HMG-CoA reductase
3. HMG-CoA produce acetyl CoA and acetoacetic acid via HMG-CoA lyase
4. acetoacetic acid and NADH produce NAD and beta HOB via beta HOBDH

THIS IS HAPPENING IN MITOCHONDRIAL MATRIX!!!!!!!

• liver
  • increase glyconeogenesis, cause increase glucose
  • increase gluconeogenesis, cause increase glucose
  • increase urea cycle
  • increase Ala
  • gluconeogenesis becomes the main way for maintaining blood glucose level
  • increase ketogenesis (concentration of 3 mM) (ratio of 3:1 favoring beta HOB over acetoacetate), increase ketone bodies
  • increase uptake of free fatty acids
  • increase beta oxidation
• muscle (PROTEIN MAIN SOURCE OF ENERGY)
  • increase proteolysis, cause increase in glucogenic AA's (esp. Ala, Gln)
  • increase free FA uptake, increase in energy production
• adipose cells
  • increase lipolysis, cause increase FA's and glycerol
• pancrease (closer to day 5)- slight increase in insulin to slow down lipolysis in muscle and drop blood glucose
• brain- adjust to metabolize ketone bodies
• decrease basal metabolic rate, so we can be more efficient in producing ATP
• turn off production of digestive enzymes

• level off of proteolysis
• how long you are in this stage depends on how overweight you are (stay until you deplete your fat stores)
  • adipose becomes main source of energy, so increased lipolysis
• 60% of brain energy comes from ketone bodies

• protein is yet again the main source of energy
  • breakdown of collagen, lead to increase blood Lys levels
• increased lactate, pyruvate, glycerol production to produce some glucose
• liver and kidney perform gluconeogenesis
  • use Lys (1/3 of collagen)

At a certain nitrogen deficit, you could not maintain life. Cause of death is typically immune system compromise where opportunitistic fungi begin to infect the individual.

• there are no digestive enzymes, so the solid food acts to pull water into GI tract
• causes severe diarrhea that will kill them

Feed them soups and liquids to rehydrate them.

• metabolically, they are same
• during stage 1 of starvation, your ketone bodies, fatty acid productions should level off due to the slight increase in insulin
• with a diabetic, ketone bodies never level off, and they just keep going up and up without being inhibited because NO INSULIN
  • metabolic system is running without any "control", so its full blast

• not due to low insulin, but HIGH glucagon in relation to insulin
• also due to receptor is not receptive to insulin
• they have very high blood sugars (making glucose in spite of high concentration)

• keton body concentratoin drops slightly
• quick affect of ratio
  • 3:1 ratio of beta HOB to acetoacetate

• glucosuria (exceed Tm)
• osmotic diuresis (loss of water due to OH's on the glucose) → dehydration (level of dehydration depends on how much you drink) → hypovolemic
• hypovelmia cause lack of perfusion to the tissues → lactic acidosis, accumulation of nitrogen compounds (due to kidney failure)
• ketone bodies excreted in the urine

• glucose acted on via aldoreductase, giving us sorbitol (cant leave cell), pulls water in, messes up crystallin, cause cataracts
• microhemorrage in eye's vasculature
• thickening of basement membrane in kidney (see filtration barrier), leads to decrease filtration
• amino groups on protein react with glucose to form Schiff's base, make amadoryl rearrangement, form permanent CB with glucose
  • this reaction can occur in LDL, so that that receptor may not bind to the correct receptor
• glycate Hb (form HbA1c)
• nerve cells uptake inositol (very similar to glucose) and make phosphatidyl inositol (increase calcium...), but glucose BLOCK inositol uptake
  • effect nerve cells with extremely long bodies (mainly in legs and arms)
  • no inositol, we cant move nutrients through the nerve
  • thats why we check feet (cause they will have a nail in their foot, they wont feel it and gangrene can result)