Integration of Metabolism

and Energy Production

Dr. Said Al Riyami

 Fuel Metabolism

• Fuel is obtained mainly from carbohydrates, fats and

proteins in our diet.
• Food in our diet is digested and absorbed. The products of
digestion circulate in blood, enter various tissues and are
eventually taken up by cells and oxidized to produce
energy and produce various body components.
• Complete oxidation with production of maximum amount
of energy from food requires oxygen.
• The end products of metabolism are CO2 and water.

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 Fuel Metabolism

• Food that exceeds the body’s immediate energy needs is

stored, mainly as FAT (triglycerides in adipose tissue), but
also as GLYCOGEN in the liver and muscle, and as
PROTEIN in muscle.
• During sleep and between meals, and during periods of
prolonged fasting, fuel is drawn from these stores and
oxidized to produce energy.

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 Fuel Stores

• Our major fuel store is fat, (85% of stored energy).

• Fat is stored in adipose tissue as triglyceride, located
mainly in the abdomen, hips and thighs.
• Another important fuel store is glycogen, a carbohydrate
stored mainly in the liver, but also in skeletal muscles.
• Glycogen stores are much smaller than those of fat.

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 Fuel Stores

• Maintaining a normal blood glucose level at all times

is vital.
• During periods when food is being eaten (digested
and absorbed), blood glucose is easily maintained.
• Liver glycogen is used to maintain blood glucose
level between meals. Therefore, unlike fat stores, the
size of glycogen stores fluctuate during the day.
(around 200g after a meal, but only 80g after an
overnight sleep)

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 Fuel Stores

• Muscle glycogen also supplies energy for muscle

contraction during exercise.
• Protein has many important roles in our body. But it may
also serve as fuel store for energy production during long
fasts.

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 Energy Production through Fuel
Oxidation

• Molecules in fuels that are oxidized to produce

energy are GLUCOSE (carbohydrate), FATTY
ACIDS (lipids), and AMINO ACIDS (proteins).

• Before oxidation, these are all converted to Acetyl

CoA in the mitochondria. Acetyl CoA then enters the
tricarboxylic acid (TCA) cycle (Krebs’ Cycle).

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 Energy Production through Fuel
Oxidation
• The TCA cycle is a series of reactions that complete the
oxidation of these fuels to CO2 and water. During the
process, electrons are produced, which are used by the
mitochondria to produce ATP from ADP by a process
called OXIDATIVE PHOSPHORYLATION.

• Oxidative phosphorylation takes place in the

mitochondria in a complex system called the electron
transport chain.

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 CARBOHYDRATES
LIPIDS
PROTEINS

MITOCHONDRI
A ACETYL COA

(Aerobic)
KREBS
’
CYCLE
ELECTRON Electron carriers (NADH &
TRANSPORT FADH2)
CHAIN
ATP (oxidative
phosphorylatio
n)
 The Body States in terms of Energy
Availability
• In terms of energy availability, the body may be viewed
as being in two states:

– A Fed State where there is continuous external supply

of energy
– A Fasting state where there is no external supply of
energy, and the body must rely on its fuel stores to
produce energy.

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 The Fed (Absorptive) State

• The fed or absorptive state is the period from the start of

absorption until absorption is completed.
• During this stage, fuel (food) is abundant, and may be
oxidized for energy or stored. This depends on the
relative concentration of two hormones in blood,
INSULIN and GLUCAGON.
• During the fed state the pancreas is stimulated to release
insulin, and release of glucagon is reduced to a minimum.

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• Insulin works mainly on
GLUCONEOGENESI
S
• Liver cells: Inhibits
GLYCOGENOLYSIS
gluconeogenesis and LIPOLYSIS
glycogenolysis. Also stimulates STO
P KETOGENESIS
glycogenesis PROTEOLYSIS

• Muscle cells: Stimulates

glycogenesis and increases the
number of glucose transporters INSULI
therefore increasing glucose uptake N
by cells.
GLUCOSE UPTAKE IN
• Adipose tissue (fat): Increases the MUSCLE & ADIPOSE
number of glucose transporters TIEESUE
GO
therefore increasing glucose uptake.
GLYCOLYSIS
GLYCOGENESIS
PROTEIN SYNTHESIS
• The net effect of these processes is
a drop in blood glucose.
 Fate of Glucose After a Meal
• The liver is the first organ through which glucose passes
after absorption.
• In the liver, insulin promotes the uptake of glucose by
increasing its use as a fuel (glycolysis, TCA cycle) and its
storage as glycogen (glycogenesis) and triglyceride
(lipogenesis). Cells may also use glucose in biosynthetic
reactions.
• Liver glycogen stores reach a maximum of about 200 to
300g after a carbohydrate meal.
• As the glycogen stores begin to fill, the liver begins to
convert excess glucose to triglycerides.

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 Fate of Glucose After a Meal

• These are then packaged with proteins, phospholipids,

and cholesterol into VLDL, which are secreted into the
bloodstream.

• Some fatty acids from VLDL are taken up by tissues and

used for energy, but most are stored in adipose tissues as
triglycerides.

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 Fate of Lipoproteins in the Fed State

• Two types of lipoproteins, chylomicrons and VLDL, are

produced in the fed state.
• Their function is to transport triglycerides in blood.
• As chylomicrons and VLDL pass in the blood vessels,
their triglycerides are removed and degraded to fatty
acids and glycerol.
• The rest of their metabolism has been explained earlier.
• Eventually they get stored in adipose tissue, which has a
limitless capacity to store fat.

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 Fate of Amino Acids in the Fed State

• Amino acids absorbed from the intestine travel directly to

the liver, where they are used for the synthesis of all types
of proteins. They are also used in the synthesis of other
molecules (Nitrogen containing molecules).
• Amino acids are not utilized for energy production
normally. In certain circumstances, the liver can oxidize
amino acids for energy production or convert them into
glucose and ketone bodies, (discussed later).
• Proteins in the body are constantly being synthesized and
broken down (protein turnover/ amino acid pool).

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 The Fasting State
• Blood glucose level peaks approximately 1 hours after a
meal, and then decreases as tissues oxidize glucose for
energy or convert it to storage forms.
• Fasting begins about 2 – 4 hours after a meal, when blood
glucose level returns back to basal levels.
• The drop in blood glucose causes a decrease in the
production of insulin by the pancreas.
• This is a signal for the liver to start breaking down its
glycogen stores and release glucose into the blood.
• If fasting continues, glucagon starts to rise and causes
more release and synthesis of glucose.

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 Blood Glucose and the Role of the Liver
during Fasting
• The liver plays a major role in maintaining blood
glucose level during fasting.
• Initially liver glycogen stores are broken down to supply
glucose to the blood. This pathway is known as
glycogenolysis. But glycogen stores are limited.
• When glycogen stores are depleted, after a long fast of
around a day or so, the liver maintains blood glucose by
another method known as gluconeogenesis, where
glucose is made from non-carbohydrate sources such as
amino acids, glycerol and lactate.

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 Role of Adipose Tissue during Fasting
• The drop in insulin level and the rise in glucagon level
during prolonged fasting stimulate lipolysis, breakdown
of lipids, (triglycerides).
• Triglycerides stored in adipose tissue are the major source
of energy during prolonged fasting.
• Fatty acids from triglycerides are oxidized for energy
production in many tissues.
• Lipolysis during fasting produces large amounts of fatty
acids which saturate the liver’s capacity to oxidize, and
fatty acids are then not completely oxidized to CO2 and
water but partially oxidized to ketone bodies, which are
then completely oxidized by other tissues (not the liver)
to produce energy.
• Ketogenesis is therefore a sign of prolonged fasting. 21
 Role of Protein in Prolonged Fasting
• Proteins have no role in energy production during
the fed state.
• But during prolonged fasting (low insulin and high
glucagon), when glucagon stores have been
depleted, and fat stores are at their minimum,
breakdown of proteins (proteolysis) occurs to
provide energy.
• How?
• Amino acids from proteolysis serve as carbon
sources for glucose production by gluconeogenesis.
Glucose is then oxidized (glycolysis, TCA cycle to
produce ATP.

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