AMINO ACID METABOLISM

Dr.B.RENGESH | M.Tech., Ph.D.

Associate Professor, Department of Pharmaceutical Technology,
Mahendra Engineering College (Autonomous),
Namakkal District, Tamil Nadu, India
 INTRODUCTION
• Triglycerides (fats and oils) are important dietary sources of energy. Fat also
functions as a major form of energy storage (9 Cal/g).
– Because it is water-insoluble, fat can be stored in larger quantities than
carbohydrates.
– Carbohydrate reserves are depleted after about 1 day without food, but stored
fat can provide needed calories for 30-40 days.
• Amino acids are the building blocks for proteins, they provide C and N for the
synthesis of other biomolecules, and they are also sources of energy (4 Cal/g).
 Digestion of Triglycerides
• During digestion, triglycerides are hydrolyzed to glycerol, fatty acids, and
monoglycerides:

• Phosphoglycerides are also hydrolyzed to their component substances (glycerol,

fatty acids, phosphate groups, and aminoalcohols).
 Chylomicrons
• The smaller molecules that are produced, along with cholesterol, are absorbed into
cells of the intestinal mucosa (the innermost layer of the gastrointestinal wall), where
resynthesis of the triglycerides and phosphoglycerides occurs.
• For transport within the aqueous environment of lymph and blood, water-insoluble
triglycerides, phosphoglycerides, and cholesterol are complexed with proteins to
form lipoprotein aggregates called chylomicrons. These aggregates can pass into the
lymph system and then into the bloodstream.
• Chylomicrons are modified by the liver into smaller lipoprotein particles, the form in
which most lipids are transported to various parts of the body by the bloodstream.
 Digestion
&
Absorption
of
Triglycerides
 Fat Mobilization and Glycerol Metabolism
• When cells need fatty acids for energy, the endocrine system produces several
hormones, including epinephrine, which interact with adipose tissue, stimulating the
hydrolysis of triglycerides to fatty acids and glycerol, which enter the bloodstream.
This process is called fat mobilization.
• The glycerol hydrolyzed from triglycerides can provide energy to cells. It is converted
to dihydroxyacetone phosphate in two steps:

– Dihydroxyacetone phosphate is one of the chemical intermediates in glycolysis. It is

converted to pyruvate, and thus contributes to cellular energy production & the pyruvate
can also be converted to glucose through gluconeogenesis.
Fatty Acid Spiral
• There are four reactions in this pathway:
 Ketone Bodies
• As the concentration of acetyl CoA builds up, the excess is converted in the liver to
the ketone bodies acetoacetate, β-hydroxybutyrate, and acetone

• These ketone bodies are carried by the blood to body tissues, mainly the brain, heart,
and skeletal muscles, where they may be oxidized to meet energy needs

üKetonemia üKetosis
üKetonuria üKetoacidosis
 AMINOACID METABOLISM
• The most important function of amino acids (about 75% of amino acid utilization) is
to provide building blocks for the synthesis of proteins in the body.
• The amino acids that are used in this maintenance come from the amino acid pool of
the body.
• The process in which body proteins are continuously hydrolyzed and resynthesized is
called protein turnover.
– The turnover rate, or life expectancy, of body proteins is a measure of how fast
they are broken down and resynthesized, expressed as a half-life.
• Plasma proteins = 10 days • Enzyme and polypeptide hormones = as
• Hemoglobin = 120 days short as a few minutes. (Insulin = 7-10
minutes)
• Muscle protein = 180 days
• Collagen = as high as 1000 days
 Amino Acid Metabolic Pathways
• Amino acids in excess of immediate body requirements cannot be stored for later use.
– The N atoms are converted to either ammonium ions, urea, or uric acid (depending on
the organism), and excreted.
– Their carbon skeletons are converted to pyruvate, acetyl CoA, or one of the intermediates
in the citric acid cycle and used for energy production, the synthesis of glucose through
gluconeogenesis, or conversion to triglycerides.
 Amino Acid Catabolism – Fate of ‘N’ atoms
• The N atoms in amino acids are either excreted or used to synthesize other N-
containing compounds. There are three stages in nitrogen catabolism:
– Stage 1: Transamination
– Stage 2: Deamination
– Stage 3: Urea Formation
 Amino Acid Catabolism – Fate of ‘N’ atoms – Transamination
• In the tissues, amino groups freely move from one amino acid to another, under the
influence of enzymes called amino tranferases or trans aminases.

Example:

The net effect of this reaction is to exchange the NH3+ on the amino acid with a =O.
 Amino Acid Catabolism – Fate of ‘N’ atoms – Transamination
• Another important example of transamination is the production of aspartate, which is
used in Stage 3, urea formation:

• This process is an important method for the bio-synthesis of the nonessential amino
acids glutamate and aspartate from a variety of other amino acids.
 Amino Acid Catabolism – Fate of ‘N’ atoms – Deamination
• This phase of amino acid catabolism uses the glutamate produced in Stage 1.

oxidative deamination

– This reaction is the principal source of NH4+ in humans.

• The NADH produced in this stage enters the electron transport chain and eventually
produces 2.5 ATP molecules.
• Other amino acids can be catabolized by oxidative deamination in the liver by
enzymes called amino acid oxidases.
 Amino Acid Catabolism – Fate of ‘N’ atoms – Urea Formation
• The ammonium ions released by the glutamate dehydrogenase in Step 2 are toxic,
and must be prevented from accumulating hence they are converted to carbamoyl
phosphate, the fuel for the urea cycle. This compound is synthesized in the
mitochondria from NH4+ and HCO3-
UREA CYCLE
 Amino Acid Catabolism – Fate of ‘N’ atoms – Urea Formation
• The net reaction for carbamoyl phosphate formation and the urea cycle is:

• After urea is formed, it diffuses out of liver cells and into the blood. It is then filtered
out by the kidneys, and excreted in the urine.
• The excretion of ammonium along with acidic ions is a mechanism that helps the
kidneys to control the acid-base balance of body fluids.
 Biosynthesis of Non-Essential Amino Acids
• The key starting materials for the synthesis of 10 nonessential amino acids are
intermediates in glycolysis and the citric acid cycle:
 Biosynthesis of Non-Essential Amino Acids
• Tyrosine is produced from the essential amino acid phenylalanine:

• Three nonessential amino acids (glutamate, alanine, and aspartate) are synthesized
from a-keto acids via transamination:

– The transaminases adjust the relative proportions of amino acids to meet the needs of
the body, since most of our diets do not contain amino acids in the exact proportions
needed by the body
 Biosynthesis of Non-Essential Amino Acids
• Asparagine and glutamine are formed from aspartate and glutamate by reaction of the
side-chain carboxylate groups with ammonium ions:

• The synthesis of arginine, cysteine, glycine, proline, and serine are considerably
more complex.