metabolism in tissues

Question 1

liver (7)

Answer 1

Heptocytes metabolize all 3 nutrients (CHO, AA, lipids)
Major role: provide energy precursors to all tissues
Maintains blance b/n nutrient suplly and precursor demand
Nutrient supply: varies with diet and feeding
Precursor requirement: varies with level of activity and health
Has remarkable flexibility in enzymatic machinery
Enzymes are sensitive to various hormones (insulin, glucagon, epinephrine, leptin)

Question 2

metabolism in adipose tissue (white vs brown)

Answer 2

WAT:

- Under skin, aroud major blood vessels and abdomen
- Adipocytes- one lipid droplet
- Energy source: glucose
- Capable of FA synthesis from glucose- insulin sensitive
- Major storage of TAG
- TAG- hydrolysis to NEFA (epinephrine sensitive)

BAT:
- Under skin (chest and back)
- Only in children, not in adults
- Many mitochondria and high blood supply - brown color
- Many lipid droplets
- FA- beta oxidation
- Non-shivering thermogenesis- thermogenin (UCP1) ** MAJOR ROLE= maintain body temp
Preadipocyres can differentiate into BAT in adults during chronic cold exposure

Question 3

metabolism in muscle

Answer 3

• Skeletal muscle can use FA, ketone bodies and glucose for energy
  
  • Resting: FA from adipose and ketone bodies from liver
  • Moderate: blood glucose in addition to FA and ketone bodies
  • Glucose undergoes aerobic glycolysis
  • Vigorous: stored glycogen gives glucose
  • Each glycogen origin glucose give 3 ATPs during glycolysis: Comes out from glycogen as glucose 1-phosphate so dont need the first ATP usually used on the first step of glycolysis
  • Anaerobic glycolysis- lactic acid
  • Phosphocreatine buffers ATP
  • Creatine - dietary or de novo (Gly, Arg, Met)
  • Epinephrine helps in using glucose from blood and glycogen
  • Shivering thermogenesis
  • Recovery from activity: lactate is converted to glucose in liver
  • Buffer system for ATP- phosphocreatine to creatine during activity
  • Recovery from activity - creatine to phosphocreatine
    So mainatin a pool of phosphate that will be used to put on ATP
    The more phosphocreatine is maintain in the muscle, the faster will be synthesize of ATP

Question 4

cardiac muscle

Answer 4

• Aerobie metabolism
  
  • Abundant mitochondria
  • Mainly FA, but can also use ketone bodies and glucose
  • Less stored glycogen
    Sensitive to O2 deprivation

Question 5

metabolism in brain

Answer 5

• Neurons- highly dependent on glucose for energy
  
  • Metabolism uses 130g glucose/day
  • Can use B-hydroxybutyrate (one of the 3 ketone bodies)
  • ATP used to maintain membrane potential (Na+ K+ATPase)
  • Astrocytes can use FA
  • Aerobic metabolism
  • No stored glycogen
  • Fasting/starvation:
    1. Ketone bodies (from FA)
    Glucose (from muscle protein)

Question 6

fuel use over 4 hours of normal metabolism

Answer 6

• Immediately after meal, glucose increases: glycolysis and gluconeogenesis increase (insulin)
  
  • 2 hours post-prandial, glucose begins to drop: liver glycogen releases glucose (glucagon)
    4 hours post-prandial, more glucagon: more TAG hydrolysis, FA become major fuel

Question 7

fuel metabolism in prolonged fasting

Answer 7

1. Protein degradation yields glucogenic AA
   
   • • non-essential AA are deaminated
       2. Urea is exported to the kidney and exctreted in urine
   3. TCA intermediate (oxaloacetate) is diverted into gluconeogenesis
   4. Glucose is exported to the brain via the bloodstream
   5. FA (imported from adipose tissue) are oxdized as fuel, prodeucing acetyl-coa
   6. Lack of oxaloacetate prevents acetyl-coa entry into the TCA; acetyl-coa accumulates
   7. Acetyl-coa accumulation favors ketone bodies synthesis
   8. Ketone bodies are exported via the bloodstream to the brain, which use them as fuel
      Excess ketone bodies end up in urine

Proteins containing Lys-Phe-Glu-Arg-Gln sequence - preferentially depleted in liver and heart

Question 8

2 forms of diabetes metillus

Answer 8

1. Type 1: insufficient production of insulin
   
   • Usually due to autoimmune destruction of B-cells
   • Usually develops early in life
     2. Type 2: insulin resistance
   • Usually develops in late adulthood
   • Cells do not respond appropriately to insulin
   • Typically INSR signaling is affected- IRS proteins are dephosphorylated
     GLUT4 is sequestred in cytoplasm

Question 9

diabetes symptoms

Answer 9

• In both forms, blood Glucose is elevated: increased osmolality- excessive urination and thirst
  
  • Proteins get glycosylated
  • In type 1, fat breakdown accelerated, leads to high ketone bodies:
    1. Raise blood concentration of H+, leads to ketoacidosis
    2. Bicarbonate buffering system activated, leads to altered breathing pattern
    3. Breakdown of ketone body acetoacetate produces acetone, which is expelled via the breath
    Untreated diabetes leads to dramatic weight loss

Question 10

adiposity- obesity

Answer 10

• Adipose tissue is also an endocrine organ
  
  • Release peptide hormones called adipokines:
    1. Carry information about fuel stores to brain
    Ex: leptin, adinopectin

Question 11

leptin - obesity hormone

Answer 11

From adipose tissue: reduces apetite
First identified in obese mice: homozygous ob/ob mice ate continually, obese, elevated cortisol, shivered, infertile, insulin resistance, died early
When leptin was injected, the mice lose weight, temp. Returned to normal
BUT, leptin administration to most obese people do NOT restore normal body mass (they have higher level of leptin)
Db/db mice were obese and diabetic
Db gene encodes leptin receptor (lepr) in brain (expressed mostly in hypothalamus)