METABOLISM OF PROTEINS

Dr. Lotfi S. Bin Dahman M.D.; Ph.D.

Clinical Biochemistry
HUCOM
 PROTEINS
• Proteins are polymers built from one or more
unbranched chains of amino acids.
• A typical protein contains 200 to 300 amino
acids
• Proteins are organic compounds formed of
amino acids joined together by peptide bonds
• Primary role of amino acids serve as building
blocks for the synthesis of body proteins
 ESSENTIAL AMINO ACIDS
• All 20 types of amino acids are required for
protein synthesis. These amino acids can be
derived from digesting dietary protein and
absorbing their constituent amino acids or,
alternatively, by synthesizing them de novo.
• 10 amino acids cannot be synthesized in
humans and therefore must be provided from
dietary sources. These are called the essential
amino acids.
ESSENTIAL AMINO ACIDS
 CLASSIFICATION OF PROTEINS
• Enzymes: proteins that catalyze biochemical reactions,
normally found intracellularly, but are released into
bloodstream as a result of tissue damage (transaminases,
dehydrogenases, phosphatases)
• Hormones: chemical messenger proteins; control the
action of specific cells or organs, directly affect growth and
development, metabolism, sexual function, reproduction
and behavior (insulin, testosterone, growth hormone, FSH
and cortisol)
• Storage Proteins: serve as reservoirs for metal ions and amino
acids such as ferritin
 CLASSIFICATION OF PROTEINS
• Transporting Proteins: involved in the transport of ions,
hormones, vitamins, minerals and lipids across a biologic
membrane (albumin, hemoglobin, ceruloplasmin,
transferrin)
• Immunoglobulins: proteins that are produced by B cells
(lymphocytes) in the bone marrow, mediate the humoral
immune response to identify and neutralize foreign
antigens (IgG, IgM, IgE, and IgA)
• Structural Proteins: collagen, elastin and keratin
• Energy source: Some proteins serve as an energy source
for tissues and muscle such as creatine
 DIETARY PROTEINS
• Dietary proteins are the primary source of the nitrogen
that is metabolized by the body.
• Dietary proteins are digested to amino acids in
the stomach and intestine, which are absorbed
by the intestinal epithelium, transferred to the
circulation, and taken up by cells.
• Amino acids are used to synthesize proteins and other
nitrogen-containing compounds.
• The carbon skeletons of amino acids are also oxidized for
energy, and the nitrogen is converted to urea
and other nitrogenous excretory products
AMINO ACIDS METABOLISM
 AMINO ACIDS OXIDATION
• Protein obtained from the diet or from body protein
during prolonged fasting or starvation may be used as an
energy source.
• Body protein is catabolized primarily in the muscle and in
liver.
1. Amino acids released from proteins usually lose their
amino group through transamination or deamination.
2. Carbon skeletons can be converted in the liver to:
I. Glucose (glucogenic amino acids)
II. Acetyl CoA and ketone bodies (ketogenic)
III. Or both may be produced (glucogenic and ketogenic).
 Amino Acids Oxidation
• Before the carbon skeletons of amino acids
are oxidized, the nitrogen must be removed.
• Amino acid nitrogen forms ammonia, which is
toxic to the body.
• In the liver, ammonia and the amino groups
from amino acids are converted to urea;
nontoxic, water-soluble, and readily excreted
in the urine.
 REMOVAL AND EXCRETION OF AMINO
GROUPS
• Excess nitrogen is eliminated from the body in urine.
• Most excess nitrogen is converted to urea in the liver
and goes through the blood to the kidneys, where it is
eliminated in the urine.
• Amino groups released by deamination reactions form
ammonium ion (NH4+)
• Elevated concentration of ammonia in blood causes
cerebral edema, convulsions, coma and death.
• Most tissues add excess nitrogen to the blood as
glutamine .
• Muscle sends nitrogen to the liver as alanine
 Glutamine Synthetase
• It is found in most tissues including muscle,
which captures excess nitrogen by aminating
glutamate to form glutamine.
• Glutamine is a relatively nontoxic substance, is
the major carrier of excess nitrogen from
tissues.
 Glutaminase
• Glutaminase is secreted by the kidneys, liver and
intestine
• The kidneys allowing glutaminase to deaminate
glutamine arriving in the blood and to eliminate
amino group as ammonium ion in urine.
• Kidney glutaminase is induced by chronic
acidosis, in which excretion of ammonium may
become the major defense mechanism.
• Intestinal bacteria and glutamine contribute to
the intestinal ammonia entering the portal blood
 Aminotransferases (Transaminases)

• Both muscle and liver have aminotransferases

(ALT & AST); transfers amino group from one
carbon skeleton (amino acid) to α-
ketoglutarate.
• Pyridoxal phosphate (PLP) is required to
mediate transfer of amino group
• In pathologic conditions, these enzymes may
leak into the blood, where they are useful
clinical indicators of damage to liver or muscle.
Alanine Transferase ALT (GPT)
 Aspartate Transaminase AST (GOT)
COO COO

COO CH2 COO CH2

CH2 CH2 CH2 CH2

HC NH3+ + C O C O + HC NH3+

COO COO COO COO

aspartate -ketoglutarate oxaloacetate glutamate

Aminotransferase (Transaminase)

Alanine Transaminase ALT (GPT)

COO COO

CH2 CH2

CH3 CH2 CH3 CH2

HC NH3+ + C O C O + HC NH3+

COO COO COO COO

alanine -ketoglutarate pyruvate glutamate

Aminotransferase (Transaminase)
OXIDATIVE DEAMINATION
FATE OF AMINO ACIDS CARBONS AND
NITROGEN
 Sources & Fate of Amino Acids

Non essential a.a.s

Diatery proteins Tissue proteins
synthesized in the body
a.a.s

Amino acid pool

Anabolism Catabolism(Deamination)
Synthesis of Fate of deamination products

Proteins Other nitrogenous compounds α- keto acid Ammonia

Krebs
►Aminosugars
►Tissue proteins cycle
►Nitrogenous bases
►Plasma proteins of phospholipids Synthetic Catabolic
►Enzymes ►Purines & pyrimidines glucose Ketone bodies CO2+H2O
►Some hormones +ENERGY pathway pathway
►Neurotransmitters
►Milk ►Niacin
►Creatine
►Heme Non essential
glutamine Excreted
a.a.synthesis Urea
in urine
 NITROGEN BALANCE
• Nitrogen balance is the (normal) condition in which the amount of nitrogen
incorporated into the body each day exactly equals the amount excreted.
Negative nitrogen balance occurs when nitrogen loss exceeds incorporation and is
associated with:
1. Protein malnutrition (kwashiorkor)
2. A dietary deficiency of even one essential amino acid
3. Starvation
4. Uncontrolled diabetes
5. Infection
Positive nitrogen balance occurs when the amount of nitrogen incorporated
exceeds the amount excreted and is associated with:
6. Growth
7. Pregnancy
8. Convalescence (recovery phase of injury or surgery)
9. Recovery from condition associated with negative nitrogen balance
 Diseases Related to Protein
Metabolism
In Adults In Infants
I. Kwashiorkor: deficiency of dietary protein only ,
Hypoproteinemia causes: leads to:
 Edema  Anemia
 Edema of legs and feet
 Muscle weakness  Vomiting
 Anorexia (loss of appetite)
 Anemia  Hepatomegaly
 Infection  Generally children of age 1-5 years

II. Marasmus: deficiency of dietary protein,

carbohydrate and fat, leads to:
 Underweight
 Old person face
 Muscle wasting
 Fatigue
 Hair changes
 Diarrhea
Marasmus Kwashiorkor
 Generally children under one year
 Regulation of Protein Metabolism
Anabolic hormones Catabolic hormones
1. Insulin 1. Cortisol
2. Growth hormone 2. Thyroid hormones
3. Androgen (large doses)

4. Thyroid hormones
(normal doses)