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Key Points
Metabolic interrelationship among
macronutrients
The central role of the liver in metabolism
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Metabolic interrelationship among the
macronutrients
Each of the macronutrients (carbohydrate, lipid
and protein) can provide human cells with
energy, as well as being involved in both anabolic
and catabolic reactions in human cells
Anabolic reactions: require energy
Catabolic reactions: produce energy (e.g.
Infection, trauma which results in rapid loss ofmuscle due to break down of body stores for
energy)
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Metabolic interrelationship among the
macronutrients
The metabolic interrelationship amongcarbohydrates, lipids and proteins in the humanbody is well established
For example: Excess dietary carbohydrate is fattening excess
glucose is known to slow down lipolysis andcontribute to the synthesis of triglycerides for storage(glucose is converted to fat via acetyl CoA)
Important amino acids can be synthesised fromglucose and fatty acids
Muscle protein is used for energy in catabolic states
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Metabolic interrelationship among the
macronutrientsNote that some
reactions are
reversible (indicated
by a return arrow)
or irreversible
(indicated by asingle arrow)
Also note that the
glycerol from
triglycerides can
enter glycolysis astriose phosphate
through a number
of conversion steps
(not shown)
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Metabolic interrelationship among the
macronutrients
Glycogenesis occurs in the liver and muscle
during fed-state
Glycogenolysis occurs during fasting state
Gluconeogenesis occurs during starvation
(essential to maintain optimal BGL to provide
brain and RBCs)
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Metabolic interrelationship among the
macronutrients
-oxidation (break down of fatty acids toacetyl CoA for ATP production)
Takes 2 carbons from the FFA at a time producing
acetyl CoA (through a number of steps) Acetyl CoA can not be used to make glucose as it
lacks sufficient carbons
Excess accumulation of Acetyl CoA leads to the
saturation of the TCA cycle This results in shunting of accumulated Acetyl CoA
to produce ketones
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The Central role of the liver in
metabolism
The liver plays a key role of processor and
distributor in metabolism, furnishing by way
of the bloodstream a proper combination of
nutrients to the organs and tissues.
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The Central role of the liver in
metabolism
Carbohydrate Metabolism
Dietary glucose is phosphorylated by glucokinase (and
hexokinase to a lesser extent) in the liver to glucose-6-
phosphate (this occurs to trap it in the cell) Other dietary monosacccharides (e.g. Fructose,
galactose) are also phosphorylated and rearranged to
glucose-6-phosphate into the liver
Catabolism of glucose-6-phosphate can result ATP
production from the hepatocytes via the aerobic
pathways (TCA cycle and oxidative phosphorylation)
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The Central role of the liver in
metabolism
Carbohydrate Metabolism
There are several anabolic routes taken by
glucose-6-phosphate, including:
Glycogenesis (formation of glycogen)
Lipogenesis (formation of fatty acids and triglycerides
via acetyl CoA)
Cholesterogenesis (formation of cholesterol via acetyl
CoA)
Nucleotide synthesis (pentose phosphate pathway)
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The Central role of the liver in
metabolism
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The Central role of the liver in
metabolism
Amino Acid Metabolism
The liver is the most active organ in amino acid
metabolism in both the fed and fasting states
The liver is the site for the synthesis of important
structural and plasma proteins (e.g. Albumin,
clotting factors)
Amino acids are also converted in the liver intonon-protein compounds which require nitrogen
(e.g. Nucleotides, hormones and porphyrins)
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The Central role of the liver in
metabolism
Amino Acid Metabolism
Catabolism of amino acids can take place in the liver
where they are transaminated (removal of NH3) and
degraded to acetyl CoA and other TCA intermediates The urea cycle in the liver removes the NH3 (and its
excreted as a waste product)
Acetyl CoA and TCA intermediates are used as follows:
Oxidised for ATP production
Glycogenesis
Lipogenesis
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The Central role of the liver in
metabolism
Amino Acid Metabolism
During fasting, amino acids from muscle protein
breakdown to provide the chief substrate for
gluconeogenesis (making new glucose)
The carbon of the amino acids from muscle
protein is delivered to the liver via the alanine-
glucose cycle
Alanine is an amino acid which is very easily
formed when a NH3 is transferred to pyruvate
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The Central role of the liver in
metabolism
The Alanine-glucose cycle
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The Central role of the liver in
metabolism
The Alanine-glucose cycle
This is very important in the maintenance of BGLs
during fasting
When these stores are depleted it is a key stage in
changing from the fasting state to the starvation
state (brain becomes reliant on ketones for energy
and substrates available for gluconeogenesis are
depleted)
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The Central role of the liver in
metabolism
Fatty Acid Metabolism
Most of the dietary fatty acids are removed fromchylomicrons and stored in adipose tissue
The liver is the major site of fatty acid synthesis. Excess
glucose and amino acids are used to make fatty acids They fatty acids made in the liver can be assembled into
liver triglycerides, with much of the triglycerides thenbeing transported via the VLDLs to the adipose tissue forstorage
Chylomicrons: lipoproteins carrying exogenous lipids Other lipoproteins (VLDL, LDL, IDL, HDL): lipoproteins
carrying endogenous lipids
(HDL= good cholesterol; others = bad cholesterol)
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The Central role of the liver in
metabolism
Fatty acid metabolism
The metabolic pathway called -oxidation is very
important in the liver. It breaks down (oxidises)
fatty acids into the 2-carbon compound Acetyl-CoA
Acetyl-CoA is used by the liver for
ATP production Cholesterogenesis
Ketogenesis
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The Central role of the liver in
metabolism
Ketones
Important as an overflow pathway for excess
Acetyl CoA
Ketones are used as an energy source during the
starvation phase
Ketogenesis most important function is getting
rid of excess Acetyl-CoA
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The Central role of the liver in
metabolism
Formation of ketone bodies (ketogenesis)
The ketone bodies include: acetoacetate, -hydroxybutyrate and acetone
Ketogenesis is an overflow pathway in the liver that deals
with excess Acetyl-CoA. It also provides the liver with away of distributing fuel to other tissues
Other tissues (e.g. Heart, kidneys) convert the ketonesback to acetyl-CoA for energy production through the TCAcycle
Brain can use ketones for energy only during starvation
Ketosis (high blood ketone levels occurs in starvation) thiscan result in keto-acidosis
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References
Gropper SS, Smith JL, Groff JL. Advanced
Nutrition and Human Metabolism. 5th Edition.
Wadsworth Cengage Learning, California