Mod.A. Bio Lec11: Proteins Flashcards
Protein is formed from
alpha amino acids linked together
by peptide bonds.
Amino acids pool (definition, site, composition
ما هي ؟؟ - : It is the amount of amino acids available in free form in the whole body
مكانها - : The liver participation is about 50%.
1- : مكوناتها - high Conc. e.g. glutamine and glutamate 50% of this pool
2- low Conc. e.g. tryptophan, cysteine and tyrosine.
Sources of amino acid pool:
1- Dietary protein
2- Hydrolysis of body protein
3- Synthesis of non essential A.A
Essential amino acids
Isoleucine - Leucine - Lysine -Methionine - Phenylalanine - Threonine - Tryptophan - Valine
Non-essential amino acids
11
Alanine - Asparagine - Aspartate -Cysteine - Glutamate - Glutamine - Glycine – Proline - Serine - Tyrosine
Tyrosine is classified as non essential, why ?
Tyrosine is synthesised from essential amino acids (phenylalanine).
Fate of Amino Acid
1-Synthesis of specialized products
and Synthesis of small peptides e.g. glutathione.
2-Synthesis of body proteins
3-Catabolism (transamination and deamination ) to -ketoacid which is used as a precursor for glucose, ketone,fa and in TCA cycle
-Ammonia is turned to urea
Carbon skeletons of glucogenic amino acids
are degraded to pyruvate precursors for gluconeogenesis.
Carbon skeletons of ketogenic amino acids
are degraded to: acetyl-CoA and acetoacetate. for energy in Krebs Cycle, or converted to ketone bodies or fatty acids.
The carbon skeletons of the twenty amino acids are brought back to only six molecules:
1)Acetyl CoA 2)Pyruvic acid 3)Oxalacetic acid 4)α- ketoglutaric 5)Succinyl CoA 6)Fumarate
Transamination (definition, site, enzyme, coenzyme)
Definition: transfer of amino group from α-amino acid to α-keto acid with formation of a new α-amino acid and a new α-keto acid.
Site: They are present either in cytoplasm or in both cytoplasm and mitochondria of most tissues.
- الإنزيم المستخدم :
enzymes called transaminases (or amino transferases). - the coenzyme : Pyridoxal phosphate (PLP= active vitamin B6)
Transaminases reactions are (reversibility)
reversible
All amino acids undergo transamination except (4)
lysine, therionine, proline, and hydroxyproline)
Types of transaminases (3)
1.Alanine transaminase(ALT) 2.Aspartate transaminase(AST) 3.Glutamate transaminase
Alanine Transaminase (ALT) (other name, reaction catalyzed, site)
also called Glutamate pyruvate transaminase (GPT)
catalyzes the transfer of amino group from alanine to α-ketoglutarate to form glutamate and pyruvate.
cytoplasm of LIVER cells
Aspartate Transaminase (AST) (other name, reaction catalyzed, site)
also called Glutamate oxaloacetate transaminase (GOT)
catalyzes the transfer of amino group from aspartate to α- ketoglutarate to form glutamate and oxaloacetate.
present in both cytoplasm and mitochondria of liver, heart and skeletal muscle cells.
AST and ALT are diagnostic enzymes of
heart and liver damage
if AST increased it indicates
in myocardial infarction, lung embolism, liver disease.
ALT increased it indicates
in liver disease
hepatitis, tumor
Types of Deamination
Oxidative deamination
Transdeamination
Oxidative deamination:
in which both oxidation (removal of hydrogen) + deamination (removal of ammonia NH3) together.
الإنزيم المستخدم L-Glutamate dehydrogenase
type of a.a: : L-Glutamate amino acid
resulting in α-ketoglutarate
- This reaction is reversible.
Its coenzyme is either NAD+ or NADP.
Transdeamination (steps)
- Step 1
transamination of
most amino acids with α-Ketoglutarate to
form glutamate (glutamate transaminase).
- Step 2
glutamate isdeaminated to
give ammonia (NH3) (oxidative deamination
by L-glutamate dehydrogenase).
- Step
3 form urea through urea cycle.
Ammonia
is a toxic substance especially to the central nervous system
be moved to the liver to be converted into urea which is less toxic
Blood ammonia: traces :10-110 μg/dl.
Urea
is the main end product of protein (amino acid) metabolism.
- is the main pathway by which the body can get rid of ammonia.
Site of urea formation and site of urea excretion
Site of formation: Liver.
: خروجها by the kidney be excreted in urine
Blood urea: is 20-50 mg/dl.
Urea cycle site
first 2 reactions occur in
other 3 reactions occur in
Site: Liver.
عدد التفاعلات :
The first two reaction occur in mitochondria
other 3 reactions occur in cytoplasm.
Step 1 of urea synthesis (site, enzyme)
Formation of carbamoyl phosphate
occurs in mitochondria and needs:
1- CO2 from TCA
2-Ammonia
3- 2 ATP molecules
Enzyme used is carbamoyl phosphate synthetase-1 (CPS-1)
what is the rate limiting enzyme of urea synthesis
CPS-1
CPS-1 is regulated by
It is activated allosterically
by N-acetyl glutamate,
is stimulated by high arginine.
Step 2 of urea synthesis
Formation of citrulline
occurs in mitochondria
- الإنزيم المستخدم : ornithine transcarbamoylase
Carbamoyl phosphate react with ornithine, producing citrulline.
Citruline then passes to cytoplasm
Step 3 of urea synthesis:
Formation of argininosuccinate
occurs in cytoplasm
الإنزيم المستخدم : It is catalyzed by argininosuccinate synthetase
Citrulline reacts with aspartate to form arginosuccinate
It utilizes one ATP and 2 high energy bonds.
Step 4 of urea synthesis:
Cleavage of argininosuccinate
occurs in cytoplasm
الإنزيم المستخدم : It is catalyzed by argininosuccinase
enzyme
Argininosuccinate is cleaved into arginine and fumarate
Fumarate produced is used to regenerate aspartic acid again
Step 5 of urea synthesis
Cleavage of arginine into ornithine and urea
occurs in cytoplasm
الإنزيم المستخدم : It is catalyzed by arginase enzyme
Arginine is cleaved to urea and ornithine.
Ornithine then passes to the mitochondria to start a new cycle
In one turn of urea cycle:
2 molecules of ammonia are consumed
1 molecule of carbon dioxide is consumed
** 3 ATP molecules and 4 high energy phosphate are utilized in this reactions.
The atoms of urea are derived from:
•Carbon atom:
from CO2 (from bicarbonate
Nitrogen atoms :
- 1st Nitrogen atom: from ammonia (from the deamination of Glutamate or Glutamine in the mitochondria )
- 2nd Nitrogen atom: from aspartate
what leads to ammonia intoxication ?
any defect in urea cycle enzymes
Ammonia Intoxication
** تسمى : hyperammonia.
Symptoms:
flopping tremors, blurring of vision and vomiting in infancy
high concentration leads to coma and death
Mechanism of ammonia intoxication :
1.At normal blood ammonia level,: any ammonia is incorporated into glutamine formation by glutamine synthetase enzyme.
2.In case of hyperammonemia, : ammonia reacts not only with glutamate, but also with α-ketoglutarate by glutamate dehydrogenase enzyme. →→ This depletes α-ketoglutarate in citric acid cycle. This results in a decrease in ATP and energy production
Inherited hyperammonemia
Result from genetic deficiency of one of five enzymes of urea cycle
- lead to mental retardation.
- most common
•Hyperammonemia type I: Due to Carbamoyl phosphate synthetase I
•Hyperammonemia type II: Due to Ornithine transcarbamoylase
Defects (of 4 enzymes) are characterized by hyperammonia ( Except one enzyme ???? No hyperammonia)
Which enzyme??
arginase
Function of phenylalanine
Phenyl alanine may enter one of the following metabolic pathways:
1-Protein biosynthesis.
2-Tyrosine synthesis by phenylalanine hydroxylase
Tyrosine
produced intercellulary from essential AA (Ph.Alanine)
- المكان : in both liver and nerves.
- وظيفته : gives the following compounds : 1- CATECHOLAMINES ( Epinephrine and norepinephrine ) 2- THYROID HORMONES ( Thyroxine ) 3- Melanine pigments
Phenylketonuria (PKU)
due to deficiency of
phenyl alanine hydroxylase or its cofactor B4 ( H4 Biopterin ).
result:
1- hyper phenylalaninaemias
Results in accumulation of phenylalanine in body fluid and central nervous system (CNS), levels may exceed 30 -80 mg/dl.
2- Phenyl alanine is increased in the blood and converted to phenyl pyruvate , phenyl lactate and phenyl acetate excreted in urine.
3- Severe mental retardation : this occurs if affected infant not treated before the age of 1 year
symptoms:
Failure to walk and talk.
Hyperactivity and tremors.
Failure to grow and IQs (intelligence quotient ) is below 50.
Skin lesion.
treatment:
Any infant should feed milk containing very low amount of phenylalanine ( phenylalanine Free Milk).
*** لاحظ أن : This regimen of diet is terminated at 6 years of age when a high concentration of phenylalanine has no longer effect on brain cells.
Albinism
طبيعة المرض : Albinismis an autosomal recessive disorder.
* السبب : due to
deficiency in tyrosinase enzyme.
بمعنى the lack synthesis of the melanin pigment, that gives color to hair, skin, and iris of the eye
results in:
1- Melanin pigments will not be formed leading to white color of skin and make it sensitive to light that may lead to burn and carcinoma.
2- Lack of pigments in hair cause fair hair
3- Lack of pigments in the eyes cause photophobia.
Alkaptonuria (AKU)
- اسم المرض : Alkaptonuria
- طبيعة المرض : an autosomal recessive disorder.
- السبب :
fail to produce the enzyme homogentisic acid oxidase which catalysis the oxidation of 2,5,dihydrophenylacetic acid (Homogentisic acid -alkapton).
- المسار الطبيعي للتفاعلات : normal oxidation of alkapton into acetoacetic acid and ultimately into H2O & CO2 does not take place.
- النتيجة :
1- alkapton is accumulated in blood and excreted in urine, which turns black upon expose to air.
فيحدث Homogentisic aciduria: elevated homogentisic acid in urine which is oxidized to dark pigment over time
2- The darkening of cartilaginous regions (pinna صيوان الأذن ) and proceed to arthritis التهاب المفاصل and generalized pigmentation of connective tissue (ochronosis).
ochronosis : مَرض يَتضمن تَرسب صَبغات قاتِمة في أنسجة الجِسم نَتيجة لتراكم حمض الهوموجنتيزيك (Homogentisic Acid) . تصبغ غضروف الأذن وتصبغ الجلد أو التهاب المفاصل . وظهور تصبغ أسود مزرق فوق الخدين والأنف والأذنين والعينين وأسطح الإصبع الإبهام والسبابة المفصلية ومنصات المفصل .
3- Dark spots in the sclera of the eyes.
4- Blue speckled discoloration of skin, particularly around sweat glands.
5- Kidney stones and prostate stones..
diagnosis of alkaptonuria (AKU)
1- Initial diagnosis is based on clinical symptoms such as urine colour and joint pain
2- Confirmed through a urine test or blood test for Homogentisic acid (HGA).
3- Genetic testing is also performed in some cases.
** Treatment of alkaptonuria
1- Restricted intake of tyrosine and phenylalanine reduces homogentisic acid and dark pigmentation
2- Pain control and certain types of exercise can reduce pain and improve mobility.
3- Patients often need surgery such as joint replacements.
4- Recently Nitisinone (antioxidant drug) may be effective in the treatment.
