Download lec3.Preferencial energy. mac2010-09

PREFERENTIAL UTILIZATION
‫ استعمال‬OF ENERGY BY
TISSUES
Dr. M. Azhar Chishti, Medical Biochemistry
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.
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
Well-fed (absorptive) state vs
Fasting/Starvation


During the absorptive ‫ االمتصاص‬state (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
continue

Metabolites ‫ المواد االيضيه‬move 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
‫‪ distribution‬االغذيه ‪Liver: “Nutrient‬‬
‫”‪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
‫‪A.‬‬
‫‪B.‬‬
The liver is considered a “nutrient
distribution center”
•
•
After a meal, the liver is bathed ‫ مغمور بـ‬in 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 عريض‬in the availability of nutrients
for the peripheral tissues.
‫‪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
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
Next
meal containing carbohydrates?

Mechanisms responsible for increased hepatic metabolism
of glucose after a meal containing
1.
2.
3.
4.
carbohydrates
Increased phosphorylation of glucose by
glucokinase
Increased glycogen synthesis
Increased activity of hexose monophosphate
pathway (HMP)
Increased glycolysis and decreased
gluconeogenesis
Mechanisms affecting hepatic fat metabolism after a meal
1.
2.
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)
Mechanisms affecting hepatic amino acids
metabolism after a meal
Increased amino acid degradation:
1.
The excess amino acids; after the synthesis of proteins and
other N2-containing molecules; are not stored, but are
either:

1.
2.
2.
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
Liver during fasting/starvation
1.  glycogen degradation
2.  gluconeogenesis
4.  KB synthesis
3.  FA oxidation
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:
1.
2.
Increased glycogen degradation maintain blood
glucose during early fasting, because liver glycogen store
is nearly exhausted after 10-18 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.
Fat metabolic response of the liver
during fasting:
1.
2.
 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.
‫العضو الثاني‬
Adipose Tissue: “Energy Storage Depot”
A.
B.
In well-fed (absorptive) state
In fasting
minimal source of
FA in human
adipose tissue
Major sources of
FA in human
adipose tissue
are:
Carbohydrate metabolism in adipose tissue
in the absorptive state ‫االمتصاص‬- ‫حاله الغذاء‬
1.
2.
3.
Increased glucose transport (insulin-dependent)
Increased glycolysis
glycerol phosphate
synthesis  used in TAG synthesis
Increased activity of HMP
NADPH
Fat metabolism in adipose tissue in the
absorptive state
1.
2.
3.
Increased synthesis of fatty acids
Increased TAG synthesis
Decreased TAG degradation (due to the
insulin-mediated inhibition of hormonesensitive lipase; HSL)
Carbohydrate metabolism in adipose tissue
in Fasting
Decreased glucose transport and metabolism
(due to low levels of insulin) decreased FA
& TAG synthesis
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:
1.
2.
A.
B.
3.
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)
‫العضو الثالث‬
Resting Skeletal Muscle
A.
B.
In well-fed (absorptive) state
In fasting
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
•
Carbohydrate metabolism in resting
skeletal muscle in the absorptive state
1.
2.
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
Amino acid metabolism in resting skeletal
muscle in the absorptive state
1.
2.
Increased protein synthesis (to replace proteins degraded since the
previous meal)
Increased uptake of branched-chain amino acids  used for:
1.
2.
protein synthesis &
source of energy
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.
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)
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
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)
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;
1.
the heart has a completely aerobic metabolism
2.
the heart contains negligible ‫ قليل‬- ‫ تافه‬energy stores, such as glycogen or
lipid.
3.


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)
‫االعضو الرابع‬
Brain
A.
B.
In well-fed (absorptive) state
In fasting
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
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.
‫العضو الخامس‬
Red Blood Cells
Red Blood Cells (RBC)



Glucose is the only fuel source for RBC
Glucose enters RBS through GLUT-1 (insulinindependent)
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
‫ملخص لجميع‬
‫االعضاء وربط‬
‫العالقه فيما بينهما‬
‫حاله الغذاء‬
‫هذا مسجد‬
‫مهم جدااا ( سؤااال )‬
‫‪THANK‬‬
‫‪YOUYou‬‬
‫‪‬‬
‫‪Thank‬‬