Biochemestry, metabolism in all organs. Details in different organs.

1. KURSK STATE MEDICAL UNIVERSITY
Student: Guilherme L. Paschoalini
Group: 29 – 2ºyear
METABOLISM IN DIFFERENT
ORGANS
KURSK - 2014

2. MACRONUTRIENTS
• Organic compounds that yield Energy
• Classified as: Carbohydrates; Fats/Lipids; Proteins
Major Metabolic Pathways:
Glycolysis
Gluconeogenesis
Glycogen Metabolism
Fatty Acid Metabolism
Citric Acid Cycle
Oxidative Phosphorylation
Amino Acid Metabolism
Only the liver can carry out all of the reaction
the major pathways.

3. Position of metabolic pathways

4. Metabolic Fate of Glucose
• Glucose: The intracellular form of glucose is glucose-6-phosphate.
• Only liver cells have the enzyme glucose-6-phosphatase that
dephosphorylates G-6-P and releases glucose into the blood for use by
other tissues
• G-6-P can be oxidized for energy in the form of ATP and NADH
• G-6-P can be converted to acetyl CoA and then fat.
• Excess G-6-P is stored away as glycogen.
• G-6-P can be shunted into the pentose phosphate pathway to generate
NADPH and ribose-5-phosphate
Metabolic Fate of Fatty Acids
• Fatty acids are oxidized to acetyl CoA for energy production in the form
of NADH.
• Fatty acids can be converted to ketone bodies. KB can be used as fuel in
extrahepatic tissues.
• Fatty acids are used for the biosynthesis of bioactive molecules such as
arachidonic acid and eicosanoids.
• Cholesterol, steroids and steroid hormones are all derived from fatty
acids.
• Excess fatty acids are stored away as triglycerides in adipose tissue.

5. Metabolic Fate of Amino Acids
• Amino acids are used for the synthesis of enzymes, transporters and
other physiologically significant proteins.
• Amino acid N is required for synthesis of the cell’s genetic
information (synthesis of nitrogenous bases).
• Several biologically active molecules such as neurotransmitters.
• Amino acids are precursors of several hormones (peptide hormones
like insulin and glucagon and Amine hormones such as
catecholamines).
• Aminoacids can be catabolized to acetyl CoA, pyruvate or
intermediates of the TCA cycle for complete oxidation
Central Themes of Metabolic Pathways
• Acetyl CoA is a common intermediate of all metabolic pathways. It
interconnects glucose, fatty acid and amino acid metabolism.
• Oxidation of dietary fuel leads to the capture of energy in the form
of ATP and NADH / FADH2.
• NADH / FADH2 transfer their electrons to O2 via the electron
transport chain. The energy released is used to synthesize ATP.
• Biosynthetic and degradative pathways are distinct and coordinately
regulated.

9. BRAIN
• Glucose is virtually the sole fuel for the human brain, except during
prolonged starvation. The brain lacks fuel stores and hence
requires a continuous supply of glucose.
• It consumes about 120 g daily, which corresponds to an energy
input of about 420 kcal
• Much of the energy, estimates suggest from 60% to 70%, is used to
power transport mechanisms that maintain the Na+-K+ membrane
potential required for the transmission of the nerve impulses.
• Overall, glucose metabolism remains unchanged during mental
activity, although local increases are detected when a subject
performs certain tasks.
• The brain cannot store glycogen, it must receive a constant supply of
glucose through the blood. Brain cells have a glucose transporter,
GLUT3,with a low Km for glucose.
• Fatty acids do not serve as fuel for the brain, because they are bound
to albumin in plasma and so do not traverse the blood-brain barrier.
In starvation, ketone bodies generated by the liver partly replace
glucose as fuel for the brain.

11. MUSCLE
• The major fuels for muscle are glucose, fatty acids, and ketone
bodies. Muscle differs from the brain in having a large store of
glycogen (1200 kcal, or 5000 kJ). In fact, about three-fourths of all
the glycogen in the body is stored in muscle
• This glycogen is readily converted into glucose 6-phosphate for use
within muscle cells. Muscle, like the brain, lacks glucose 6-
phosphatase, and so it does not export glucose. Rather, muscle retains
glucose, its preferred fuel for bursts of activity.

12. • In actively contracting skeletal muscle, the rate of glycolysis far
exceeds that of the citric acid cycle, and much of the pyruvate
formed is reduced to lactate, some of which flows to the liver, where
it is converted into glucose
• A large amount of alanine is formed in active muscle by the transamination
of pyruvate. Alanine, like lactate, can be converted into glucose by the liver.
Muscle can absorb and transaminate branched-chain amino acids; however, it
cannot form urea.

13. • Unlike skeletal muscle, heart muscle functions almost
exclusively aerobically, as evidenced by the density of
mitochondria in heart muscle. Moreover, the heart has
virtually no glycogen reserves. Fatty acids are the heart's
main source of fuel, although ketone bodies as well as
lactate can serve as fuel for heart muscle. In fact, heart
muscle consumes acetoacetate in preference to glucose.

14. ADIPOSE TISSUE
• The triacylglycerols stored in adipose tissue are an enormous
reservoir of metabolic fuel
• Adipose tissue is specialized for the esterification of fatty acids and
for their release from triacylglycerols. In human beings, the liver is
the major site of fatty acid synthesis.
• Recall that these fatty acids are esterified in the liver to glycerol
phosphate to form triacylglycerol and are transported to the adipose
tissue in lipoprotein particles, such as very low density lipoproteins
Triacylglycerols are not taken up by adipocytes; rather, they are first
hydrolyzed by an extracellular lipoprotein lipase for uptake. This
lipase is stimulated by processes initiated by insulin.
• Adipose cells need glucose for the synthesis of triacylglycerols
• Triacylglycerols are hydrolyzed to fatty acids and glycerol by
intracellular lipases.
• Glycerol derived from their hydrolysis is exported to the liver. Most
of the fatty acids formed on hydrolysis are reesterified if glycerol 3-
phosphate is abundant.

15. • Glucose level inside adipose cells is a major factor in
determining whether fatty acids are released into the
blood.

16. KIDNEY
• The major purpose of the kidney is to produce urine, which serves
as a vehicle for excreting metabolic waste products and for
maintaining the osmolarity of the body fluids. The blood plasma is
filtered nearly 60 times each day in the renal tubules.
• During starvation, the kidney becomes an important site of
gluconeogenesis and may contribute as much as half of the blood
glucose. The kidneys are a minor site of gluconeogenesis(liver is the
major site).

17. LIVER
• The metabolic activities of the liver are essential for providing fuel
to the brain, muscle, and other peripheral organs
• The liver removes two-thirds of the glucose from the blood and all
of the remaining monosaccharides. Some glucose is left in the blood
for use by other tissues. The absorbed glucose is converted into
glucose 6-phosphate by hexokinase and the liver-specific
glucokinase
• Much of the glucose 6-phosphate is converted into glycogen. Excess
glucose 6-phosphate is metabolized to acetyl CoA, which is used to
form fatty acids, cholesterol, and bile salts.
• The liver can produce glucose for release into the blood by breaking
down its store of glycogen and by carrying out gluconeogenesis.
• The main precursors for gluconeogenesis are lactate and alanine
from muscle, glycerol from adipose tissue, and glucogenic amino
acids from the diet.

18. • The liver cannot efficiently use glucose or ketone bodies as fuel. It
prefers fatty acids and α-keto acids as a source of energy for its
activities.
• Hepatic lipid metabolism:When fatty acids are in excess, they are
exported to the adipose tissue for storage as TG. TG are transported
as VLDL particles assembled from newly synthesized or dietary fatty
acids.
• In the fasting state, liver converts fatty acids into ketone bodies.

22. REFERENCES
• Biochemistry, 5th edition - Jeremy M Berg, John L Tymoczko,
and Lubert Stryer
• Lehninger Principles of Biochemistry - by Albert L.
Lehninger
• Biochemistry - Jeremy M. Berg
• Lippincott's Illustrated Reviews: Biochemistry