integration of metabolism 2013
TRANSCRIPT
Integration of Metabolism
Atif H. Khirelsied. B.Sc., M.Sc., Ph.D.
Department of BiochemistryFaculty of Medicine and Health Sciencesy
International University of Africa, Khartoum, Sudan
Metabolism During Fed (Absorptive)Metabolism During Fed (Absorptive) State
Metabolism During Fed (Absorptive) State
The fate of glucose in the liverThe fate of glucose in the liver.• Glucose is oxidized to CO2 and H2 O to meet the immediate energy needs of the liverimmediate energy needs of the liver.
• Some glucose is stored in the liver as glycogen.
• Excess glucose will be converted to fatty acids and a glycerol moiety to form triacylglycerols which areglycerol moiety, to form triacylglycerols, which are released from the liver into the blood as very‐low‐density lipoprotein (VLDL)density lipoprotein (VLDL).
Metabolism During Fed (Absorptive) State
The fate of glucose in other tissues.
• The brain, oxidizes glucose to CO2 and H2O, producing ATP.g 2 2 p g
• Red blood cells oxidize glucose to lactate.g
• Muscles aerobically oxidize glucose to generate ATP forMuscles aerobically oxidize glucose to generate ATP for contraction. They also store glycogen for use during contraction.
• Adipocytes oxidize glucose to produce ATP and glycerol used p y g p g yto produce TAGs stores.
Metabolism During Fed (Absorptive) State
The fate of lipoproteinsThe fate of lipoproteins.
f• The TAGs of chylomicrons and VLDL are hydrolyzed by lipoprotein lipase to FAs and glycerol.
• The FAs are taken up by adipose tissue, converted to triacylglycerols.
• The glycerol returns back to the liver.
Metabolism During Fed (Absorptive) State
The fate of amino acids from dietary proteinsThe fate of amino acids from dietary proteins.
• Used for protein synthesis.
• Used to make nitrogenous compounds such as heme, creatine phosphate, epinephrine, and the bases of DNA p p , p p ,and RNA.
• Excess amino acids are oxidized to generate ATP.
Metabolism During Fed (Absorptive) State Figure from BRS Biochemistry, Molecular Biology, and Genetics
Metabolism During Fasting State
Metabolism Fasting State
The liver metabolism during fating state.
• The liver produces glucose and ketone bodies that are• The liver produces glucose and ketone bodies that are released into the blood.
• Glucose is released from glycogen (Glycogenolysis) and th i d f b h d tsynthesized from non‐carbohydrates precursors
(Gluconeogenesis).
• Ketone bodies are synthesized from acetyl‐CoA generated in the β‐oxidation.
Metabolism Fasting State
The liver metabolism during fating state.
• Ketone bodies (KBs) are synthesized from acetyl‐CoA• Ketone bodies (KBs) are synthesized from acetyl‐CoAgenerated in the β‐oxidation.
• The KBs are acetoacetate and β‐hydroxybutyrate.
• The liver cannot oxidize KBs and releases them into the blood.
Metabolism Fasting State
The adipocytes metabolism during fating state.
• As glucagon levels rise adipose TAGs stores are• As glucagon levels rise, adipose TAGs stores are mobilized.
• FAs are taken up and oxidized by the liver to generate energy and KBs, the glycerol is converted to glucose.
• Tissues such as muscle oxidize the FAs to CO2 and H2O.
Metabolism Fasting State
The muscle metabolism during fating state.
• During fasting muscle protein is degraded and their• During fasting, muscle protein is degraded, and their amino acids are partially metabolized by muscle and released into the blood mainly as alanine and glutaminereleased into the blood, mainly as alanine and glutamine.
• Alanine will be taken up by the liver to synthesize glucose and the nitrogen is converted to urea.
• Glutamine is mainly used by kidneys and the gut.Glutamine is mainly used by kidneys and the gut.
Metabolism Fasting State
The muscle metabolism during fating state.
• During fasting muscle oxidizes FAs (from adipocytes)• During fasting, muscle oxidizes FAs (from adipocytes), and KBs produced by the liver.
• During exercise, muscle can also use its own glycogen stores as well as glucose from the blood.
Figure from BRS Biochemistry, Molecular Biology, and GeneticsMetabolism Fasting State
Fuels Available in the Human Body for Long Term Fasting
Normal Man Obese Man
Fuels Available in the Human Body for Long‐Term Fasting
Fuel reserve Kg Kcal Kg Kcal
Fat (adipocytes) 15 141.000 (85%) 80 752.000 (96%)
Protein (Muscle) 6.0 24.000 (14%) 8 32.000 (4%)
Glycogen (Muscles) 0.12 480 0.16 640
Glycogen (Liver) 0.07 280 0.07 280
Glucose (Extracellular Fluid) 0.02 80 0.03 100
l l blTotal Available Reserve Energy 165.840
Table from BRS Biochemistry, Molecular Biology, and Genetics
Metabolism During Starving State
Metabolism During Starvation
The metabolic changes in (prolonged fasting) starvation.
1. Muscle decreases use of KBs and oxidizes FAs as its energy1. Muscle decreases use of KBs and oxidizes FAs as its energy source.
2. Because of decreased use by muscle, blood ketone body levels riselevels rise.
3. The brain decreases its use of glucose and starts using KBs to derive energy.
Metabolism During Starvation
The metabolic changes in (prolonged fasting) starvation.
4. Liver gluconeogenesis decreases.4. Liver gluconeogenesis decreases.
5 Muscle protein is spared (i e less muscle protein is5. Muscle protein is spared (i.e., less muscle protein is degraded to provide amino acids for gluconeogenesis).
6. Less amino acids are degraded and less urea is produced from amino acid nitrogen in starvation than after an overnight fast.
Metabolism During Starving State