NUTR 475: Lecture 23- Urea Cycle

sources of ammonia

intestinal bacteria
deamination of amino acids

ammonia is highly

toxic

humans convert ammonia to

urea

urea biosynthesis

transamination
ammonia transport
oxidative deamination
reactions of urea cycle

ammonia goes from ___ tissues to ___

peripheral
liver

the glucose alanine cycle is used primarily as a mechanism for ___ ___ to eliminate ___

skeletal muscle
nitrogen

glutamine formed in the brain or muscle from ____ is transported to the ___ or ___ where ammonia is excreted

glutamate
liver
kidney

glutamate is a

neurotransmitter

ammonia is loaded onto glutamate to form

glutamine

___ removes ammonia group from glutamine

glutaminase

The ___ is the major place for detoxification of ammonia

liver

transamination of ___ and ___ removes ammonia, which is converted to urea through the urea cycle

alanine
glutamate

major end product of nitrogen catabolism

urea

98% of ammonia in the body exists as ___ and has a role as a _____ _____.

NH4
buffering system

transamination

ALT and AST

deamination

glutamate dehydrogenase (GDH)

conditions of the conversion of glutamine to glutamate to produce free ammonia to be converted to urea

high protein diet or fasting condition

activator of the conversion of glutamine to glutamate to produce free ammonia to be converted to urea

ADP

the conversion of glutamine to glutamate to produce free ammonia to be converted to urea is similar to

oxidative deamination

hydrolysis of glutamine

glutaminase

conversion of ammonia to urea occurs exclusively in the

liver

urine eliminates ___ in the kidneys

ammonia

the urea cycle is a cycle of biochemical reactions that produces ___ from ___

urea
ammonia

the urea cycle consists of 5 reactions 2 ___ and 3 ____

mitochondrial
cytosolic

the urea cycle converts __ amino groups, one from ____ and one from ___, and a carbon atom from HCO3- , to relatively nontoxic excretion product, ___

2
NH4+
Aspartate
urea

oxidative deamination occurs in the ___ and is the sequestor to the toxic ___

mitochondria
ammonia

NH4+ comes from ___ in the ___ or from ___ ___ metabolism from the ___ tissues

deamination
liver
amino acid
peripheral

the urea cycle has __ enzymes and __ amino acids

5
6

synthesis of one mole of urea requires ___ moles of ATP plus __ mole of each ammonium ion of the a-amino nitrogen of ____

3
1
aspartate

formation of carbamoyl phosphate

CO2 + NH4+ --> carbamoyl phosphate
2Mg-ATP--> 2 MG-ADP + Pi
N-acetylglutamate

formation of carbamoyl phosphate cofactor

N-acetylglutamate

formation of carbamoyl phosphate enzyme

carbamoyl phosphate synthase 1 (CPS-I)

what enzyme initiates urea biosynthesis?

carbamoyl phosphate synthase I (CPS-I)

1st step in urea cycle

formation of carbamoyl phosphate

1st ATP in the formation of carbamoyl phosphate turns ___ to ___ and ___ to ___

bicarbonate to CO2
NH4+ to NH3

activator of CPS-1

N-acetylglutamate

2nd ATP in the formation

drives rxn

formation of citrulline

L-ornithine to L-citrulline

formation of citrulline catalyzed by

L-ornithine transcarboamoylase

L-Ornithine transcarboamoylase catalyzes transfer of the ____ group of carboamoyl phosphate to ____, forming citrulline.

carbamoyl
ornithine

mitochondrial reactions

formation of carbamoyl phosphate
formation of citrulline

formation of arginosuccinate

L-citrulline + L-aspartate to arginosuccinate
Mg-ATP --> AMP _ Mg-PPi

Argininosuccinate synthase links ____ and citrulline via the ____ group of aspartate and provides the second ____ of urea.

aspartate
amino
nitrogen

Formation of argininosuccinate occurs in the

cytosol

cleavage of arginosuccinate forms

L-Arginine and Fumarate

fumarate goes to

TCA cycle

Cleavage of argininosuccinate catalyzed by

arginosuccinase

Cleavage of argininosuccinate occurs in

cytosol

cleavage of arginine occurs in

cytosol

cleavage of arginine catalyzed by

arginase

cleavage of arginine

L-arginine to L-ornithine
releases urea

Ornithine reenters the livers ____ cells for additional round of urea synthesis.

mitochondria

ornithine is a potent inhibitor of

arginase

On high-protein diets the carbon skeletons of the amino acids are oxidized for ____ or stored as ____ and glycogen, but the amino nitrogen must be ____.

energy
fat
excreted

the urea cycle operates only to eliminate

excess nitrogen

short term regulation of urea cycle

The activity of CPS-I is determined by N-acetylglutamate.

Ornithine inhibits ____. CPS-1 activity is determined by activator ____

arginase
N-acetylglutamate

long-term regulation of urea cycle: under conditions of starvation, enzyme levels ____ as proteins are degraded and amino acid carbon skeletons are used to provide energy, thus ____ the quantity of nitrogen that must be excreted

rise
increasing

when dietary proteins increase significantly, levels of enzymes involved in the urea cycle ___

rise

on return to a balanced diet, enzyme levels

decline

GDH reaction

glutamate to a-ketoglutarate
NAD+ to NADH
NH3 released

depletion of a-ketoglutarate

a-ketoglutarate to glutamate
NADPH to NADP
NH3 used

ammonia can alter blood

pH

depleting a-ketoglutarate in the brain upon conversion of a-ketoglutarate to

glutamate

ammonia can reduce neurotransmitters upon conversion of ___ to ___.

glutamate to glutamine