1. Metabolic interrelationship in well fed state  
ط      Metabolic integration during well fed state
ط     Inter-organ  relationship
ط     Hormonal balance: Insulin/glucagon ratio
                                          N L3    ;  D4  

2. Metabolic Interrelation
Well-Fed State fig13.2 D4 (Mixed Fuels)
Early-Fasting State fig13.3 D4 (3-4 hr post-absorptive period)
Fasting State fig13.4 D4 (early / Intermediate / prolonged starvation)
Re-fed State fig13.6 D4

3. Metabolic Interrelation
1. Well-Fed State fig13.2 D4 (Mixed Fuels)
- In well-fed state the diet supplies the energy requirement (Glc, AA, fat)
- increase INS : Glg ratio (Glc, AA, fat)

4. Metabolic Interrelation
1. Well-Fed State fig13.2 D4 (Mixed Fuels)
* Carbohydrate (diet) => Glc (liver) activated by INS =>
a) produce NADPH
b) stored as Glycogen
c) Oxidized to Pyruvate =>
· anaerobically produce Lactate
· complete oxidation (aerobically) through TCA cycle => CO2 + H2O
· converted to fat (G3P => glycerol) and stored in AT or muscle
- no cori cycle
Glc (liver) => other tissues activated by INS
d) Brain/Testis (main source): CO2 + H2O
e) RBCs/Adrenal Medulla (only source): Pyruvate/Lactate
f)  Adipose tissue: fat
g) Muscle: Glycogen / CO2 + H2O

5. Metabolic Interrelation
1. Well-Fed State fig13.2 D4 (Mixed Fuels)
* Protein (diet) => AA (liver) activated by INS =>
a) usually AA pass liver (↑Km Enzs, except tRNA Enz during growth) to all tissues and activated by INS =>
·  synthesize protein
·  enters the carbon skeleton & oxidized completely => CO2 + H2O
b) if concentration of dietary AA is high it does not pass the liver
·  produce urea
·  converted to fat =>transported by VLDL, stored in AT & muscle

6. Metabolic Interrelation
1. Well-Fed State fig13.2 D4 (Mixed Fuels)
* Fat (diet) => Chylomicron (lymph) =>
a) reaches Adipose tissue
·         Stored as TG
b)  reaches muscle
·         Stored TG
·         Oxidized to CO2 + H2O

7. Metabolic Interrelation
2. Early-Fasting State fig13.3 D4 (3-4 hr post-absorptive period)
- In early fasting, hepatic glycogenolysis is an important source of bld glc
Fat & prt reduce gastric emptying fig13.3 D4, fig14.1 NL3
* Glycogen (liver) activated by Glg => Glc (gluconeogenesis) => other tissues
a) Muslce: alanine cycle
b) RBCs: cori cycle
c) Brain: CO2 + H2O
- End stage: bld glc and ins are low
- no protein synthesis

8. Metabolic response to starvation
ط     Stages of starvation and hormonal balance
ط     Post absorptive period : Duration and characters
ط     Early starvation : Duration and  fuel  utilization
ط     Intermediate starvation : Duration and fuel utilization, glucose alanine and fatty acid cycle
ط     Prolonged starvation : characters and causes of death after prolonged starvation
ط     Refeeding after prolonged starvation
ط     Integration of carbohydrates, Lipid and protein metabolism during starvation
ط     Regulatory role of ketone Bodies and T3 in starvation
                                          N L ;  D4    

9. Metabolic Interrelation
3. Fasting State fig13.4 D4 (early/intermediate/prolonged starvation)
In fasting state, gluconeogenesis is required from AAs & glycerol
A. Fasting State (early starvation)
· Early stage: most tissues utilize glc fig13.4 D4, fig14.2, Table14.1 NL3
· Then: only brain & anaerobic tissues
· This will increase FA oxid in muscle & other tissues (e.g. kidneys)
· Up to 24 hours

10. Metabolic Interrelation
3. Fasting State fig13.4 D4 (early/intermediate/prolonged starvation)
A. Fasting State (early starvation)
* Glucose (liver) => Cori cycle
a) Lactate (RBCs) =>
b) Glucose (liver) =>
c) Lactate (RBCs) =>
d)Glucose (liver) =>

11. Metabolic Interrelation
3. Fasting State fig13.4 D4 (early/intermediate/prolonged starvation)
A. Fasting State (early starvation)
* Protein => AA activated by Glucagon
a) Protein (Liver) => AA => Glucose
·  Reach brain => Oxidized to CO2 + H2O
b) Protein (Muscle) => AA => Alanine / Glutamine
·  Alanine reaches liver => gluconeogenesis to glucose + urea
- Glucose reach brain => Oxidized to CO2 + H2O
- Urea reaches kidney => excreted
· Glutamine reaches Gut => Alanine
- alanine reaches liver => gluconeogenesis to glucose + urea
* glucose to brain => oxidized to CO2 + H2O
* urea to kidneys => excretion

12. Metabolic Interrelation
3. Fasting State fig13.4 D4 (early/intermediate/prolonged starvation)
A. Fasting State (early starvation)
* Fat (Adipose tissue) => Hydrolyzed to Glycerol + Fatty Acids
a)       Glycerol + Fatty Acids reach Liver
·         Glycerol => Glucose
- reaches brain => Oxidized to CO2 + H2O
·         Fatty Acids => Ketone bodies
- reaches muscle => Oxidized to CO2 + H2O
b)       Fatty Acids reaches muscle
·         Oxidized to CO2 + H2O

13. Metabolic Interrelation
3. Fasting State fig13.4 D4 (early/intermediate/prolonged starvation)
B. Intermediate Starvation
· Early stage: high gluconeogenesis (lact, glycerol, G-AA) fig14.3, Table14.3 NL3
· Later stage: high KB
· 1-24 days

14. Metabolic Interrelation
3. Fasting State fig13.4 D4 (early/intermediate/prolonged starvation)
C. Prolonged Starvation
· Low prt degrade – enz activity (AAs) fig14.4, Table14.4 NL3
· The rate of carb, lipid, prt metab reach steady state
· Constant high KB concentration
· Low N excretion
· Ends with Re-feeding or death
· Death is caused by pneumonia, low Ab, shock

15. Metabolic Interrelation
Role of KB
· 2-24 days: high KB is produced for brain, nervous tissue, kidney cortex, s.intest epithelial cells, heart
· Also decrease in glc utilization, FA oxid and prt degrad in other tissues

16. Metabolic Interrelation
Role of T3
· Thyroxine does not control metab rate
· Starve 2-3 days decrease basal metab rate (not thyroxine)
· The active for is triiodothyronine (T3)
· During starvation: decrease production of T3 from T4
Increase production of reverse-T3 from T4
· This is to control prt deg & energy expenditure
· Hypothyroid during starvation decrease prt breakdown and urea excretion and increase survival

17. Metabolic Interrelation
4. Re-fed State fig13.6 D4 (after fasting / after starvation)
In early-refed state, fat is metabolized normally and normal glucose metabolism is slowly re-established
A. Early Re-feeding After Fasting
· Glc is the main fuel in breakfast fig13.6 D4, fig14.10 NL3

18. Metabolic Interrelation
A. Early Re-feeding After Fasting
* Carbohydrate (diet) => Glc (liver) activated by INS =>
a) Glc reach brain => oxidized to CO2 + H2O
b) Glc reaches Adipose tissue => converted to fat (G3P => glycerol) and stored
c) Glc reaches muscle => stored as Glycogen
d) Glc reaches RBCs => Lactate
·  Lactate reaches liver => glc stored as glycogen

19. Metabolic Interrelation
A. Early Re-feeding After Fasting
* Protein (diet) => AA (liver) activated by INS =>
a) AA (liver) =>
·  Stored as Glycogen + release Urea
·  Protein Synthesis
b) AA reach all tissues =>
·  synthesize protein

20. Metabolic Interrelation
A. Early Re-feeding After Fasting
* Fat (diet) => Chylomicron (lymph) =>
a) reaches Adipose tissue
·  Stored as TG
b) reaches muscle
·  Stored TG
·  Oxidized to CO2 + H2O

21. Metabolic Interrelation
B. Re-feeding After Starvation
· Same as re-feeding after fasting plus high prt-AA metab
· 2 days: increase Glg, GH GC and deacrease INS lead to hogh FA, KB, Glc, AA
· 2-4 days; FA, Glc , KB ratio fig14.5 NL3