Nitrogen Metabolism Flashcards
Atmospheric nitrogen
Most abundant but is too inert for use in most biochemical reactions
Dietary proteins
N2 is acted upon by bacteria and plants to nitrogen containing compounds. We assimilate these as dietary compounds
What are the two main ways of obtaining nitrogen
Air and diet
Is there a storage form of nitrogen in humans?
No
Why must the body get rigid of any nitrogen that’s is above the needs?
Because its a reactive compound
How does most nitrogen leave the body?
Through the urea cycle
What serves to clear the body of excess nitrogen
Urea cycle
Urea cycle
Serves to clear the body of any excess nitrogen by also retaining any “carbon skeletons” of the nitrogen containing compounds for other uses
How does most nitrogen enter the body?
In the form of amino acids
Input of the amino acids in the amino acid pool?
- Amino acids from dietary protein
- Amino acids from protein turnover in the body
- Synthesis of non-essential amino acids de novo
Out of amino acids
- Synthesis of proteins
- Synthesis of other nitrogen containing compounds (nucleotides and heme)
- Use of the “carbon skeleton” of AA for other compounds (glucose, lipids., ketone bodies), or for energy
What has to be balanced for the individual to be in a steady state?
Input and output
Selectively degrade damaged or short lived proteins
Proteasomes
What do proteasomes use to target proteins for degradation
Ubiquitin modification
What do proteasomes require?
ATP, energy dependent
Nonselectively degrade intracellular proteins (autophagy( and extracellular (heterophagy)
Lysosomes
What do lysosomes use to break down peptide bonds
Acid hydrolases
How much protein do we get a day in the diet?
~100g
Where is protein digested ?
Stomach and small intestine
Enzyme in the stomach that breaks down protein
Pepsin
Enzymes in the small intestine that breaks down protein
- pancreatic enzymes
- intestinal wall cells
Pancreatic enzymes
- trypsin
- chymotrypsin
- elastase
- carboxyl emptied
Intestinal wall cells
- aminopeptidases
- di and tripeptidases
What roles do HCL play?
- killing microorganism
- aiding digestion as it helps denature proteins
- converts pepsinogen to active pepsin
Absorption from the lumen into the enterocytes
- free AA
- di and tripeptides
Free AA
Absorbed into the lumen into the enterocytes by a sodium linked secondary transport systme of the apical membrane
Absorption from the lumen into the enterocytes of di and tripeptides
By a proton-linked transport system
Peptides in the enterocytes
- Peptides are hydrolyzed in the cytosol to amino acids
- AA released into the portal system
What is found in the portal vein after a meal containing protein?
Only Free AA
What organ plays a central role in absorption and transport of amino acids?
Liver
What role does liver play in absorption and transport of AA?
-Liver determines which amino acids will be releases into general circulation and how much
Branch chained amino acids
Are not metabolizes by the liver bu instead are sent from the liver primarily to muscle via the blood
Removal of nitrogen from AA
- Transamination
2. Oxidative deamination
Transamination
Transfer of the AA a-amino group to a-ketoglutarate producing an a-keto acid (derived from the original AA) and glutamate
Oxidative deamination
Results in the liberation of the amino group as free ammonia
- these reactions occur primarily in the liver and kidney
- also happens in the mitochondria
What is the enzyme that plays a role in the transport of ammonia to the liver as glutamine?
Glutamine synthetase
Transport of ammonia to the liver as glutamine
- free NH3 is added to glutamate to make glutamine
- occurs in many tissues
- bathe form to release nitrogen into the bloodstream for transport to the liver
What is the enzyme responsible for the transport of ammonia to the liver as alanine?
ALT
Transport of ammonia to the liver as alanine
- ALT
- transamination of pyruvate
- mainly in muscle cells
- in the liver, Ala is converted to pyruvate, again by transamination (the glucose-alanine cycle)
What are names for the urea cycle
Ornithine cycle
Urea cycle
-a cycle of biochemical reactions occurring in that produces urea from ammonia
Where does the urea cycle primarily take place in mammals?
Liver, and to a lesser extent the kidney
What does the urea cycle consist of?
5 reactions
- 2 mitochondrial
- 3 cytsosolic
Is the urea cycle catabolic or anabolic?
Catabolic, ATP is used.
Is the synthesis of urea reversible or irreversible?
Irreversible, with a large -deltaG
What is the immediate precursor for both ammonia?
Glutamate
What is one nitrogen of the urea molecule supplied by?
Free NH3 and the other nitrogen is asparatate
Sources of ammonia
- Dietary amino acids
- From glutamine
- From bacterial action
- From amines
- From the catabolism of purines and pyrimidines
How much ammonia is always in the blood?
A low constant level
Is amonia toxisc or nah?
Super toxic
How is amino acid transported in the blood?
- an amino group as part of an AA
- urea
Free ammonia
Will be removed by the liver and used for synthesis of urea
What do kidneys do other than removing urea from circulation
Produce some free ammonia, via glutaminase
Where is free ammonia realized into?
Urine
-contributes to the acid-base balance of the body by excreting protons (ammonium ion)
Elevated levels of ammonia in the blood
Hyperammonemia
Hyperammonemia is a symptom of what?
Liver failure
Any condition that interferes with liver function can lead to what
Hyperammonemia
What happens if you have elevated ammonia (above 1000micomols/l)?
Ammonia intoxication which is a medical emergency
What can cause blurring of vision
Elevated of ammonia
What do the carbon skeletons of amino acids shuttle into?
Pathways we have already seen
What can the carbon skeletons of AA acids be converted into?
- intermediates of the TCA cycle
- pyruvate
- acetyl coA
- acetoacetate
What are the glucogenic things that the carbon skeleton of AA can be converted into?
- Intermediates of the TCA cycle (OAA, fumarate, succinyl CoA, a-ketoglutarate
- pyruvate
Ketogenic things that the carbon skeletons of the AA can be broken down into?
- acetyl CoA
- acetoacetate
Glucogenic catabolism
An amino acid athat can be converted into pyruvate or an intermediate of the TCA cycle. They may be used as substrates for gluconeogensis, therefore their breakdown can give rise to a net increase in glucose formation in the liver
An amino acid that can be converted into pyruvate or an intermediate of the TCA cycle can be used for what?
Gluconeogensis
What does the breakdown of glucogenic amino acids cause an increase in?
Net increases in glucose formation in the liver
Ketogenic amino acid
Amino acids that can be converted into acetoacetate or a precursor to acetoacetate
Precursor for acetoacetate
-acetyl coA or acetoacetyl coA
What are the nonessential glucogenic amino acids?
- alanine
- arginine
- asparagine
- aspartate
- cysteine
- glutamine
- glutamate
- glycine
- proline
- serine
Essential glucogenic amino acids
- histidine
- methionine
- threonine
- valine
Which nonessemtial amino acid is both glucogenic and ketogenic?
Tyrosine
What essential amino acids are both glucogenic and ketogenic
- isoleucine
- phenylalanine
- tryptophan
What essential amino acids are ketogenic?
- leucine
- lysine
Which nonessential amino acids are ketogenic?
None
Nonessential amino acids
Can be synthesized by biochemical pathways in the human cells
Essential amino acids
Lack enzymes necessary, so they cannot be synthesized by humans to meet the metabolic demand of the body
Conditionally essential amino acids
An amino acids that would normally be considered nonessential but may become ‘essential’ to meet an increases demand
When does elevated homocysteine occur?
During methionine metabolism
How many disposal pathways are there for Hcy requiring vitamins?
2
What do elevations in plasma Hcy promote?
Oxidative damage, inflammation, and endothelial dysfunction
What are elevations in plasma Hcy risk factor for?
Independent risk factor for occlusive vascular disease
Elevated Hcy during pregnancy is associated with
Increases incidence of neural tube defects
Eye anomalies associated with homocystinuria
- ectopia lentis
- myopia
- glaucoma
- optic atrophy
- retinal detachment
- cataracts
What is homocystinuria
The disease is due to a deficiency in cystathionine synthase
What is albinism a defect in?
A number of enzymes that are involved in the conversion of tyrosine to melanin
A defect in a number of enzymes that are involved in the conversion of ________ to _______ will cause albinism.
- tyrosine
- melanin
What is the most severe form of albinism
Complete albinism
What enzyme is deficient in complete albinism
Tyrosinase
What does complete albinism result in?
Complete lack of pigment
What enzyme deficiency causes a complete lack of pigment?
Tyrosinase
What are albino patients at increased risk for?
Skin cancer
What is a source of methyl groups in metabolism?
Methionine
Member of urea cycle, precursor of nitric oxide
Arginine
Transport of ammonia, precursor for nucleotide biosynthesis
Glutamine
Precursor of histamine
Histidine
Precursor of serotonin
Tryptophan
Precursor for catecholamines
Tyrosine
Transport of ammonia (muscle)
Alanine
