FORM & FUNCTION (Starvation 1) Flashcards
Starvation and obesity
-2 extreme disturbances to energy metabolism
-can occur in all species
Stages of starvation
-specific sequence by which body consumes energy sources
>early (glucose)
>intermediate (fatty acid and ketone)
>late (protein
Insulin : Glucagon ratio (high insulin)
-increase sugar storages
>glucose uptake and trapping (GLUT4/glucokinase)
>glycogenesis (glycogen synthase)
-increase making fat
>lipogenesis (acetyl-CoA carboxylase): rate-limiting step
>FA transport (lipoprotein lipase)
Insulin : Glucagon ratio (high glucagon)
-increase use/make sugar
>glycogenolysis (glycogen phosphorylase)
>gluconeogenesis (PEPCK mRNA levels)
-increase use of fat
>lipolysis (release insulin’s inhibitory effect on HSL)
>ketogenesis (HMG-CoA synthase)
Metabolic fate of glucose following a meal:
- Glucose as endogenous fuel
- Glycogen storage
- Fat synthesis
Glucose utilization in post-absorption:
glycogen is the first energy source used
-muscle: provide metabolic fuel
-liver: maintain blood glucose
>vital source of energy for the brain
Post-absorptive period:
-short
>glycogen storage is only modest
64kg mammal glycogen storage:
-liver: 70g (only thing that can be used to increase glucose levels)
-muscle; 286g
Resting vs. physical activity energy utilization: (glycogen capacity)
-resting: 21 to 26 kCal/day/kg (about 20 hrs) of body weight
-physical activity (or cold exposure): 70-90 kCal/day/kg (about 6 hours)
65kg animal triglyceride storage:
-almost 12kg
Fat oxidation: early starvation
-as glycogen depletes, next source is fat
-total fat storage could potentially provide several weeks of survival fuel (20-60days)
Early starvation steps:
- Fat breakdown increases and beta-oxidation becomes the primary source of fuel
- Gluconeogenesis is increased to support energy for the brain
Lipolysis review:
- Cortisol levels rise in starvation
- No insulin to inhibit HSL activity
- Glycerol molecules recycled for gluconeogenesis
- FFA are shuttle to tissues
Gluconeogenesis activation:
-glucose is still needed for brain and RBC
*cannot use the FA
-use glycerol
Ketogenesis:
-cells cannot keep up with glucose demand
*must start to synthesize ketones
Conditions of ketogenesis:
- Depletion of CHO (primary metabolic fuel)
- Activation of FA oxidation to generate ATP
- BUT, when glucose is low oxaloacetate is used for gluconeogenesis and acetyl-CoA cannot be converted to citrate to enter the TCA
- Excess acetyl-CoA is shuttled into ketogenesis, which circulate in the blood to feed other tissues
Effects of ketone utilization:
*more than 70% of energy requirement non-glucose (ketone bodies and protein)
-ketonemia and ketoacidosis
Ketonemia:
-1-2mM (3-4days) to 6-10mM (week 2)
-can lead to ketoacidosis
Ketoacidosis
-increased anion gap
Starvation insulin : glucagon (high glucagon, low insulin):
-Carbs: decrease glycogen synthase, increase glycogen phosphorylase
-Fat: increase hormone-sensitive lipase, decrease acetyl-CoA carboxylase
-Alternate fuel: increase PEPCK, increase HMG-CoA synthase
Sequence of metabolic adjustment in starvation:
-as exogenous glucose decreases, hepatic glycogenolysis increases
>then gluconeogenesis and plasma FFA
*maximal hepatic synthesis of plasma KB at 3-5 days of starvation
Starvation complications:
-steatosis
-ketoacidosis
Steatosis:
-fatty liver disease
-rate of lipolysis EXCEEDS capacity to use them
-O2 consumption reduced by 10-15% (decreased basal metabolic rate)
-lipolysis rate exceeds aerobic metabolism
-excess FFA re-uptake in the liver, exceeds the rate of export
Fatty liver:
-malnutrition impairs VLDL assembly
>protein synthesis requiring ATP is reduced in the liver)
-common in cats (stress, diabetes)
-jaundice
Jaundice:
-liver unable to process bilirubin
>bilirubin formed when hemoglobin is breakdown=yellow pigment
Ketoacidosis:
*surge of ketone production as alternative source of fuel causes a decrease in HCO3-
-H+ produced removes HCO3- or Cl-
>results in an increased anion gap
Consequence of ketoacidosis:
-drop in blood pH leads to metabolic acidosis
