1. Preferential Utilization استعمال of Energy by Tissues
Dr. M. Azhar Chishti, Medical Biochemistry

2. Objective
To understand the different ways of energy utilization by various organs
To be familiar with: how fuel availability during absorptive state affects different organs’ energy utilization relative to fasting state. 

3. Lecture Outline
1. Overview of the major ways in which glucose is metabolized in selected tissues
2. Inter-tissue relationships in absorptive and starvation states:
A-    Liver
B-    Brain
C-    Skeletal muscle and heart
D-    Adipose tissue
E-  Red blood cells
F- Kidneys

4. Well-fed (absorptive) state vs Fasting/Starvation
During the absorptive الامتصاص state (which is the 2 to 4hour period after ingestion of a normal meal), virtually واقعيا , ALL tissues use glucose as a fuel.
While during fasting/starvation various organs use different fuels to obtain energy

5. continue Metabolites المواد الايضيه move between tissues.
An “organ map” will be introduced in this lecture.
The goal of this “organ map” is to create an expanded and clinically useful vision of whole-body metabolism

6. Liver: “Nutrient الاغذيه distribution center”
In well-fed (absorptive) state
In fasting
طريقه المحاضره
بيعطيك اربع او خمس اعضاء
كل عضو يعطيك اياه على فترتين ( الصيام والغذاء )
ويعلمك في كل فتره وش بيصير للكاربوهيدرات والبروتين والدهون

7. The liver is considered a “nutrient distribution center”
After a meal, the liver is bathed مغمور بـ in blood containing absorbed nutrients and elevated levels of insulin secreted by the pancreas. These reached the liver through the hepatic portal vein before entry into the general circulation.
Thus , the liver smoothes out potentially broad fluctuations تغير عريض in the availability of nutrients for the peripheral tissues.

8. Major metabolic pathways in liver in the absorptive state
تلخص كل العمليات بالكبد
# طريقه هذا الدكتور يعطيك صوره مثل هذي ثمن يشرح في الشرائح اللي بعدها

9. The liver is normally a glucose-producing rather than a glucose-using tissue.
However, after a meal containing carbohydrate, the liver becomes a net consumer of glucose.
What are the mechanisms responsible for this  in hepatic metabolism of glucose after a meal containing carbohydrates?
Next

10. Increased phosphorylation of glucose by glucokinase
Mechanisms responsible for increased hepatic metabolism of glucose after a meal containing carbohydrates
Increased phosphorylation of glucose by glucokinase
Increased glycogen synthesis
Increased activity of hexose monophosphate pathway (HMP)
Increased glycolysis and decreased gluconeogenesis

11. Mechanisms affecting hepatic fat metabolism after a meal
Increased fatty acid synthesis
Increased triacylglycerol (TAG) synthesis  packaged into very-low-density lipoprotein (VLDL) particles secreted into the blood  to be used by extrahepatic tissues (particularly adipose & muscle tissue)

12. Mechanisms affecting hepatic amino acids metabolism after a meal
Increased amino acid degradation:
The excess amino acids; after the synthesis of proteins and other N2-containing molecules; are not stored, but are either:
Released into the blood for all tissues to use in protein synthesis (especially the branched-chain amino acids which cannot be degraded by the liver, and are preferentially metabolized in muscle)
Degraded to pyruvate, acetyl CoA, or TCA cycle intermediates energy production or fatty acid synthesis
Increased protein synthesis

13. Liver during fasting/starvation
 glycogen degradation
 gluconeogenesis
 KB synthesis
 FA oxidation

14. Carbohydrate metabolic response of the liver during fasting:
The primary role of liver during fasting is maintenance of blood glucose for use by other organs.
This takes place through the following mechanisms:
Increased glycogen degradation maintain blood glucose during early fasting, because liver glycogen store is nearly exhausted after hrs of fasting.
Increased gluconeogenesis: starts 4-6 hrs after the last meal and becomes fully active as stores of liver glycogen are depleted; i.e. maintain blood glucose during prolonged fasting.

15. Fat metabolic response of the liver during fasting:
 FA oxidation: FA are from adipose tissue and represent the major source of energy for the liver for postabsorptive state.
 Ketone bodies synthesis: starts during the first days of fasting, can be used as fuel by most tissues, including the brain. Although KB synthesis occurs in the liver, the liver cannot use KB as fuels.

16. Adipose Tissue: “Energy Storage Depot”
العضو الثاني
Adipose Tissue: “Energy Storage Depot”
In well-fed (absorptive) state
In fasting

17. minimal source of FA in human adipose tissue
Major sources of FA in human adipose tissue are:

18. Carbohydrate metabolism in adipose tissue in the absorptive state حاله الغذاء -الامتصاص
Increased glucose transport (insulin-dependent)
Increased glycolysis glycerol phosphate synthesis  used in TAG synthesis
Increased activity of HMP NADPH

19. Fat metabolism in adipose tissue in the absorptive state
Increased synthesis of fatty acids
Increased TAG synthesis
Decreased TAG degradation (due to the insulin-mediated inhibition of hormone- sensitive lipase; HSL)

20. Carbohydrate metabolism in adipose tissue in Fasting
Decreased glucose transport and metabolism (due to low levels of insulin) decreased FA & TAG synthesis

21. Fat metabolism in adipose tissue in Fasting
Increased TAG degradation (due to hormonal activation of HSL)
Increased FA release from TAG degradation. These FA are either:
released into blood  to tissue to be used as fuel
converted to acetyl CoA in adipocytes  TCA  energy production
Decreased FA uptake (due to low activity of lipoprotein lipase in adipose tissue in fasting)

23. Resting Skeletal Muscle
العضو الثالث
Resting Skeletal Muscle
In well-fed (absorptive) state
In fasting

24. Energy metabolism of skeletal muscle
Skeletal muscle is able to respond to substantial changes in the demand for ATP.
At rest, muscle accounts for ~ 30% of the O2 consumption of the body.
During vigorous muscle exercise, muscle accounts for up to 90% of the total O2 consumption

25. Carbohydrate metabolism in resting skeletal muscle in the absorptive state
Increased glucose transport (insulin-dependent) glucose metabolism  energy for the muscle (Glucose is the 1ary source of energy for muscle in the well-fed state)
Increased glycogen synthesis

26. Amino acid metabolism in resting skeletal muscle in the absorptive state
Increased protein synthesis (to replace proteins degraded since the previous meal)
Increased uptake of branched-chain amino acids  used for:
protein synthesis &
source of energy

27. Fat metabolism in resting skeletal muscle in the absorptive state
FA are of secondary importance as a fuel for muscle during the absorptive state.
In the absorptive (well-fed) state; glucose is the primary source of energy for skeletal muscle.

28. Carbohydrate metabolism in resting skeletal muscle in Fasting
Depressed glucose uptake and metabolism in skeletal muscle in fasting (due to low levels of circulating insulin)

29. Amino acid metabolism in resting skeletal muscle in Fasting
During the first few days of fasting  rapid protein breakdown (muscle proteolysis)  AA to be used by the liver for gluconeogenesis  maintain adequate blood glucose level for brain energy requirements
Several weeks of fasting  decreased rate of muscle proteolysis (the brain has begun using KB as a source of energy

30. Fat metabolism in resting skeletal muscle in Fasting
First 2 weeks of fasting: the source of energy for muscle are:
FA oxidation (FA are from adipose tissue)
KB from liver
After ~ 3 weeks of fasting: the source of energy for muscle is:
FA oxidation (FA are from adipose tissue) (while KB are spared for the use of brain as a fuel)

31. Differences between heart muscle and skeletal muscle energy requirements
Heart muscle differs from skeletal muscle in three important ways:
the heart is continuously active, whereas skeletal muscle contracts intermittently on demand;
the heart has a completely aerobic metabolism
the heart contains negligible تافه - قليل energy stores, such as glycogen or lipid.
Thus, any interruption of the vascular supply, for example, as occurs during a myocardial infarction, results in rapid death of the myocardial cells.
Fuels used by heart muscle
Glucose
free fatty acids (FFA)
ketone bodies (KB)

32. االعضو الرابع
Brain
In well-fed (absorptive) state
In fasting

33. Carbohydrate & fat metabolism in brain in the absorptive state
The brain completely depends on the availability of blood glucose as a fuel.
Little contribution of FA to energy production to brain (FA do not efficiently cross the blood-brain barrier)
~140g glucose/day

34. Carbohydrate & fat metabolism in brain in the Fasting/starvation state
During the first few days of fasting: The brain continues to use blood glucose exclusively as a fuel.
Prolonged fasting (> 2-3 weeks) plasma Ketone bodies replace glucose as the 1ary fuel for the brain.

35. العضو الخامس
Red Blood Cells

36. Red Blood Cells (RBC) Glucose is the only fuel source for RBC
Glucose enters RBS through GLUT-1 (insulin- independent)
Glucose is then metabolized as follows:
mainly by glycolysis to produce energy & 2,3 Bisphosphoglycerate (Anaerobic glycolysis since RBC has no mitochondria)  lactate into blood
HMP  NADPH Protective antioxidant function

37. ملخص لجميع الاعضاء وربط
العلاقه فيما بينهما
حاله الغذاء

38. حاله الصيام

39. ملخص كامل

40. هذا مسجد
مهم جدااا ( سؤااال )
Thank you 
Thank You