Mod.A. Bio Lec11: Proteins

Question 1

Protein is formed from

Answer 1

alpha amino acids linked together

by peptide bonds.

Question 2

Amino acids pool (definition, site, composition

Answer 2

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.

Question 3

Sources of amino acid pool:

Answer 3

1- Dietary protein

2- Hydrolysis of body protein

3- Synthesis of non essential A.A

Question 4

Essential amino acids

Answer 4

Isoleucine - Leucine - Lysine -Methionine - Phenylalanine - Threonine - Tryptophan - Valine

Question 5

Non-essential amino acids

11

Answer 5

Alanine - Asparagine - Aspartate -Cysteine - Glutamate - Glutamine - Glycine – Proline - Serine - Tyrosine

Question 6

Tyrosine is classified as non essential, why ?

Answer 6

Tyrosine is synthesised from essential amino acids (phenylalanine).

Question 7

Fate of Amino Acid

Answer 7

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

Question 8

Carbon skeletons of glucogenic amino acids

Answer 8

are degraded to pyruvate precursors for gluconeogenesis.

Question 9

Carbon skeletons of ketogenic amino acids

Answer 9

are degraded to: acetyl-CoA and acetoacetate. for energy in Krebs Cycle, or converted to ketone bodies or fatty acids.

Question 10

The carbon skeletons of the twenty amino acids are brought back to only six molecules:

Answer 10

1)Acetyl CoA 2)Pyruvic acid 3)Oxalacetic acid 4)α- ketoglutaric 5)Succinyl CoA 6)Fumarate

Question 11

Transamination (definition, site, enzyme, coenzyme)

Answer 11

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)

Question 12

Transaminases reactions are (reversibility)

Answer 12

reversible

Question 13

All amino acids undergo transamination except (4)

Answer 13

lysine, therionine, proline, and hydroxyproline)

Question 14

Types of transaminases (3)

Answer 14

1.Alanine transaminase(ALT) 2.Aspartate transaminase(AST) 3.Glutamate transaminase

Question 15

Alanine Transaminase (ALT) (other name, reaction catalyzed, site)

Answer 15

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

Question 16

Aspartate Transaminase (AST) (other name, reaction catalyzed, site)

Answer 16

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.

Question 17

AST and ALT are diagnostic enzymes of

Answer 17

heart and liver damage

Question 18

if AST increased it indicates

Answer 18

in myocardial infarction, lung embolism, liver disease.

Question 19

ALT increased it indicates

Answer 19

in liver disease

hepatitis, tumor

Question 20

Types of Deamination

Answer 20

Oxidative deamination

Transdeamination

Question 21

Oxidative deamination:

Answer 21

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.

Question 22

Transdeamination (steps)

Answer 22

1. Step 1

transamination of
most amino acids with α-Ketoglutarate to
form glutamate (glutamate transaminase).

2. Step 2

glutamate isdeaminated to
give ammonia (NH3) (oxidative deamination
by L-glutamate dehydrogenase).

3. Step

3 form urea through urea cycle.

Question 23

Ammonia

Answer 23

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.

Question 24

Urea

Answer 24

is the main end product of protein (amino acid) metabolism.

• is the main pathway by which the body can get rid of ammonia.

Question 25

Site of urea formation and site of urea excretion

Answer 25

Site of formation: Liver.

 : خروجها by the kidney be excreted in urine

Blood urea: is 20-50 mg/dl.

Question 26

Urea cycle site
first 2 reactions occur in
other 3 reactions occur in

Answer 26

Site: Liver.
 عدد التفاعلات :
The first two reaction occur in mitochondria
other 3 reactions occur in cytoplasm.

Question 27

Step 1 of urea synthesis (site, enzyme)

Answer 27

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)

Question 28

what is the rate limiting enzyme of urea synthesis

Answer 28

CPS-1

Question 29

CPS-1 is regulated by

Answer 29

It is activated allosterically
by N-acetyl glutamate,

is stimulated by high arginine.

Question 30

Step 2 of urea synthesis

Answer 30

Formation of citrulline

 occurs in mitochondria

• الإنزيم المستخدم : ornithine transcarbamoylase

 Carbamoyl phosphate react with ornithine, producing citrulline. 
Citruline then passes to cytoplasm

Question 31

Step 3 of urea synthesis:

Answer 31

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.

Question 32

Step 4 of urea synthesis:

Answer 32

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

Question 33

Step 5 of urea synthesis

Answer 33

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

Question 34

In one turn of urea cycle:

Answer 34

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.

Question 35

The atoms of urea are derived from:

Answer 35

•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

Question 36

what leads to ammonia intoxication ?

Answer 36

any defect in urea cycle enzymes

Question 37

Ammonia Intoxication

Answer 37

** 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

Question 38

Inherited hyperammonemia

Answer 38

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

Question 39

Defects (of 4 enzymes) are characterized by hyperammonia ( Except one enzyme ???? No hyperammonia)
Which enzyme??

Answer 39

arginase

Question 40

Function of phenylalanine

Answer 40

Phenyl alanine may enter one of the following metabolic pathways:
1-Protein biosynthesis.
2-Tyrosine synthesis by phenylalanine hydroxylase

Question 41

Tyrosine

Answer 41

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

Question 42

Phenylketonuria (PKU)

Answer 42

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.

Question 43

Albinism

Answer 43

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.

Question 44

Alkaptonuria (AKU)

Answer 44

• 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..

Question 45

diagnosis of alkaptonuria (AKU)

Answer 45

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.