Download urea cycle

‫متابولیسم پروتئین ها و اسیدهای آمینه‪:‬‬
‫دکتر سالمی‬
‫گروه بیوشیمی بالینی‬
‫گردش پروتئین در بدن‬
‫سرنوشت کاتابولیک اسیدهای آمینه‬
‫سرنوشت اسکلت‬
‫کربنی‬
‫سرنوشت عامل آمین‬
‫سرنوشت عامل آمین‬
‫آمونیاک‬
‫• آمونیاک ترکیب بسیار سمی برای بدن بوده و ازدیاد آن در خون‬
‫سبب بروز پدیده هایپرآمونمی ‪ hyperammonemia‬شده که‬
‫سبب بروز عالئم شدیدی در سیستم عصبی‬
‫ترانس آمیناسیون اسیدهای آمینه (‪)TRANSAMINATION‬‬
‫انتقال گروه آمین در بدن انسان‬
The urea cycle
• also known as the ornithine cycle, is a cycle
of biochemical reactions occurring in many
animals that produces urea ((NH2)2CO)
from ammonia (NH3).
• This cycle was the first metabolic cycle discovered
(Hans Krebs and Kurt Henseleit, 1932), five years
before the discovery of the TCA cycle.
• In mammals, the urea cycle takes place primarily
in the liver, and to a lesser extent in the kidney.
Step 1
• First step combines CO2 and NH4+ to form carbamoyl
phosphate
22.8 The Urea Cycle
– Reaction requires ATP and H2O
– Takes place in the mitochondria
– Catalyzed by carbamoyl phosphate synthase
‫‪‬‬
‫‪.1‬‬
‫‪.2‬‬
‫‪.3‬‬
‫‪.4‬‬
‫گروه های آمین کاربامیل فسفات می تواند از‬
‫منشاء ترکیبات زیر که به کبد می رسند تشکیل‬
‫گردد‪:‬‬
‫مقدار اندکی آمونیاکی که از طریق سیاهرگ بابی‬
‫به کبد می رسد‪.‬‬
‫گلوتامین که عامل آمین حاصل از اکثر بافت ها‬
‫را در خون حمل می کند‪.‬‬
‫آمینواسیدهایی که در بافت کبد شکسته می شوند‬
‫آمین خود را به شکل گلوتامات منتقل می کنند‪.‬‬
‫از بافت عضالنی انتقال آمین به شکل اسید آمینه‬
‫آالنین انجام می شود‪.‬‬
Step 2
• Carbamoyl phosphate condenses with the amino acid
ornithine to produce the amino acid citrulline
– Occurs in the mitochondria
– Catalyzed by ornithine transcarbamoylase
Step 3
• Citrulline is transported to the cytoplasm
– Condenses with aspartate to produce argininosuccinate
– Catalyzed by argininosuccinate synthase
– Requires energy released by ATP hydrolysis
Step 4
• Argininosuccinate cleaved to produce the amino acid
arginine and fumarate of the citric acid cycle
• Reaction catalyzed by argininosuccinate lyase
Step 5
• Final reaction hydrolyzes arginine to generate
urea – the reaction product that is excreted
• Reaction also regenerates ornithine, the original
reactant in the cycle
• Reaction is catalyzed by arginase
Urea Cycle
2
• Aspartate and
carbamoyl
phosphate each
deliver an amino
group to the
cycle.
• Notice that the
carbamoyl
phosphate
production and
condensation
occur in the
mitochondrial
matrix.
‫بخشی از سیکل‬
‫اوره در‬
‫سیتوپالسم‬
‫وبخشی در‬
‫میتوکندری است‬
1 L-Ornithine
2 carbamoyl phosphate
3 L-citrulline
4 argininosuccinate
5 fumarate
6 L-arginine
7 urea
Regulation
1. N-Acetyl glutamic acid
The synthesis of carbamoyl phosphate and the urea cycle
are dependent on the presence of NAcGlu,
which allosterically activates CPS1.
Synthesis of NAcGlu by NAGS, is stimulated by both Arg,
and Glu, both of which are elevated when free amino
acids are elevated.
So, Arg is not only a substrate for the urea cycle reactions
but also serves as an activator for the urea cycle.
Normal level of Blood Urea
• BUN( Blood Urea Nitrogen):
7–21 mg/dL
• Urea [mg/dL]= BUN [mg/dL] * 2.14
• Urea= 15- 45
Urea cycle disorders:
‫) افزایش‬NH4+( ‫در خون اوره کاهش یافته – آمونیاک‬
• Anomalies of the urea cycle:
1.
2.
3.
4.
5.
6.
7.
N-Acetylglutamate synthase
deficiency
Carbamoyl phosphate
synthetase deficiency
Ornithine
transcarbamoylase
deficiency
Hyperornithinemia,
hyperammonemia,
homocitrullinuria
syndrome (HHH syndrome,
ornithine translocase
deficiency)
Citrullinemia
Argininosuccinic aciduria
Argininemia
http://www.ureacycle.com/ :‫انیمیشن این سایت را ببینید‬
:‫افزایش اوره‬
• Azotemia: elevated conc. of urea in blood
• Very high plasma urea concentration
accompanied by renal failure is called
uremia, or the uremic syndrome
• Causes of urea plasma elevations are:
– Prerenal
– Renal
– and postrenal
‫سرنوشت اسکلت کربنی‪:‬‬
‫حدواسط های متابولیکی که از اسکلت کربنی‬
‫اسیدهای آمینه ساخته می شوند‪:‬‬
Fate of Carbon skeleton of amino acids: a keto acids
‫تقسیم بندی سرنوشت اسکلت کربنی اسیدهای‬
:‫آمینه‬
In humans, the glucogenic
amino acids are:
•
•
•
•
•
•
•
•
•
•
•
•
•
Glycine
Serine
Valine
Histidine
Arginine
Cysteine
Proline
Alanine
Glutamate
Glutamine
Aspartate
Asparagine
Methionine
In humans, the
Ketogenic
amino acids are:
• leucine
• Lysine
Amino acids that are both
glucogenic and ketogenic:
•
•
•
•
•
Isoleucine
Threonine
Phenylalanine
Tyrosine
Tryptophan
:‫تمرین‬
1.
2.
3.
4.
Write the equation for the transamination reaction between
valine and pyruvate.
Write the equation for the transamination reaction between
phenylalanine and oxaloacetate.
What products are formed in the oxidative deamination of
glutamate?
Determine if each amino acid is glucogenic, ketogenic, or both.
1.
2.
3.
5.
phenylalanine
leucine
serine
Determine if each amino acid is glucogenic, ketogenic, or both.
1.
2.
3.
asparagine
tyrosine
valine