University of Duhok

College of Medicine
Metabolism module
Session 6

Dr. Sherwan F Salih

M.B.Ch.B - F.I.B.M.S.(Chemical pathology)
Protein, amino acid
and
Nitrogen Metabolism
Learning objectives

1. State the catabolism of proteins in the body

2. List the hormones that regulate the uptake of amino acids by different
tissues
3. Enumerate the functions of amino acid
4. Expalin the metabolism of amino acids, including essential amino acids
5. State the difference between transamination and deamination
6. Describe the metabolism of nitrogen in the body
7. Describe the metabolism of ammonia in the body
8. Explain the clinical consequences of a defect in phenylalanine
metabolism
 Metabolism of protein
LO-1
o catabolism of protein
 catabolism of protein occur in
• gastrointestinal tract
 catabolism of protein occur by help of
• protease and peptidase
 catabolism of protein result in
• hydrolysis of peptide bonds,
• release free amino acids

• absorbed into the circulation

• used by tissues
o uptake of amino acids into the tissues LO-2

 skeletal muscle
 adipose tissue
 liver
• insulin
• growth hormone
o half-life of a body protein
 about 80 days

o total protein turnover in a healthy adult

 300-400 gram per day

• 100-150 gram are muscle proteins and digestive enzymes
 amino acid functions LO-3

 synthesis of protein (all 20 amino acids), 75%

 synthesis of N-compounds (specific amino acids), 25%
 oxidised to provide energy
 intermediates of carbohydrate and lipid metabolism
 synthesis of signaling molecules
• nitric oxide from L-arginine
• hydrogen sulphide from L-cysteine
 amino acid metabolism LO-4

o amino acid anabolism

 essential amino acids (nine)
amino acids must provided in the diet
• lysine, isoleucine, leucine,, valine, histidine
• tryptophan, phenylalanine, methionine, threonine
• tyrosine, cysteine (semi-essential)
diet is low in phenylalanine
diet is low in methionine
 amino acid pool
• total amount of free amino acids in the body, 100 gram
• 50% of the pool make by glutamine, alanine, proline, glycine
 amino acid synthesis LO-4
• carbon atoms of amino acid
glycolysis (C3)
pentose phosphate pathway (C4 and C5)
Krebs cycle (C4 and C5)
• amino group of amino acid
other amino acids, transamination
o amino acids catabolism LO-4

 removal of the amino group (-NH) of amino acid

• converted to urea (CO(NH2)2) excreted

from the body in the urine
 conversion of C-skeletons of the amino acids

• pyruvate, oxaloacetate
• α-ketoglutarate, succinate
• acetyl CoA, fumarate
ketogenic , synthesis of ketone body
glucogenic, synthesis of glucose
o transamination and deamination LO-5

 transamination
• removal of the amino group (-NH) of amino acid to other amino acid
transaminases
alanine aminotransferase, glutamate-pyruvate transaminase
aspartate aminotransferase, glutamate-oxaloacetate transaminase
 deamination
• removal of the amino group (-NH) of amino acid to free NH3 (NH+)

amino acid oxidases

 Nitrogen metabolism LO-6

o total amount of nitrogen in the body (70kg male)

 2.0 kg (3%)

o constitute of

 high molecular weight molecules (high N content)

• proteins (major N-compounds in the body, 90% of the nitrogen)

• DNA and RNA
 low molecular weight molecules (low N content)
• amino acids, purines, pyrimidines, hormones
• neurotransmitters, porphyrins, creatine, and carnitine
 Ammonia metabolism LO-7
o toxicity of ammonia
 clinically characterized by
• blurred vision, slurred speech
• tremor, coma and death
 molecularly characterized by
• ammonia with alpha-ketoglutarate form glutamate in mitochondria
glutamate dehydrogenase
slow, disrupting the energy supply to brain cells
interfere with neurotransmitter synthesis and release
o ammonia detoxification LO-3
 mainly occur
• liver
 pathway of detoxification
• synthesis of N-compounds, glutamine
released from the cell to the liver and kidney
hydrolysed by glutaminase releasing the ammonia
• conversion to urea and excretion in urine

• excreted directly in the urine

o urea synthesis LO-3
 urea is synthesised
• liver
urea cycle
 characters of urea
• nontoxic
• metabolically inert
• high nitrogen content (47%)
very effective way of disposing of unwanted nitrogen
 regulation of urea synthesis
• protein diet
high protein diet induces the enzymes
low protein diet or starvation represses enzymes
o inherited diseases of the urea cycle LO-3
 caused by
• complete loss of enzyme, always fatal
• partial loss of enzyme, may not be fatal
 lead to
• hyperammonaemia
• accumulation of urea cycle intermediates
 clinically
• vomiting, lethargy, irritability
• mental retardation, seizure, coma, death
 Phenylketonuria (PKU) LO-8
o defined as

 inherited metabolic disorder of amino acid, phenylalanine

o caused by
 phenylalanine hydroxylase deficiency
• no oxidation of phenylalanine to tyrosine
o diagnosed by
 phenylketones in the urine • detection
 blood phenylalanine concentration • increase
o clinically by
 inhibition of brain development
• phenylpyruvate inhibits pyruvate uptake into mitochondria
• interferes with energy metabolism in the brain
Summary
1. Insulin and growth hormone are the main hormones enhance uptake
the amino acids into the tissues

2. Amino acids are the basic unit for proteins structure

3. Essential amino acids must be supply by the diet

4. Amino acid synthesis involved many metabolic processes

5. Large amount of nitrogen present in the our body

6. Hyperammonaemia is very serious and may result in death

7. Synthesis of urea occur exclusively in liver

8. Phenylketonuria is associated with abnormal development of brain

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