Amino Acids: Disposal of Nitrogen. Flashcards
What is the chemical formula for ammonia?
NH3.
What is the chemical formula for ammonium?
NH4+.
What kind of food products are amino acids found?
In proteins.
Why do amino acids differ from other dietary foods?
Because they contain nitrogen which cannot be stored in the body.
What does the metabolism of amino acids require?
For nitrogen to disposed of in a non toxic way.
What can aminos acids be used to make?
Proteins.
Energy.
Specialised products.
How many essential amino acids are there?
10 essential amino acids.
Where do we obtain our essential amino acids from?
From the diet.
How many non essential amino acids are there?
10 non-essential amino acids.
What does the body use dietary proteins for?
To synthesise body proteins.
They can also be used to make specialised products.
They can be used as a source of energy.
What specialised products does the body use proteins to make?
Heme.
Neurotransmitters.
Nucleotides.
Can amino acids be used as precursors for gluconeogenesis?
Yes.
What is the most common amino acid that is used as a precursor for gluconeogenesis?
Alanine.
How can alanine be used to form pyruvate?
It is converted to a keto acid and then to pyruvate.
How much of a standard American diet comes from protein?
Around 20%.
What element does the metabolism of amino acids produce?
Nitrogen.
Can nitrogen be stored in the body?
No.
Why is nitrogen not stored in the body?
Because it can easily form ammonia which is very toxic, especially to the nervous system.
Are the proteins that make up the body ever degraded?
Yes.
An adult human will turnover how many grams of protein per day?
Around 400g.
What happens to the proteins that are turned over by the body?
They are combined with dietary proteins and are broken down to create a pool of amino acids.
What percentage of turned over amino acids are recycled by the body?
Around 80%.
What are the amino acids that are recycled by the body used for?
To synthesise proteins.
Energy production.
To specialised products.
What is very important to maintain in protein degradation and synthesis?
Balance.
This is called nitrogen balance.
Do all proteins have the same lifetime?
No.
Different proteins have different life spans, some can last for years and others for days or even minutes.
How many signals do are used for protein degradation?
3 signals.
What do the signals for protein degradation depend on?
The structural aspect of the protein.
Post translational modification.
What are the 3 signals for protein degradation?
Oxidation.
PEST sequences.
Ubiquitination.
What is the oxidation signal for protein degradation?
It is a generic signal that occurs if the protein has been damaged by oxidation and needs to be destroyed.
What is the PEST signal for protein degradation?
Many proteins have sequences containing 4 amino acids that form the acronym PEST in their primary structures.
These proteins have a very short half-life as their sequences are a signal for the body to destroy the protein.
What amino acids make up the PEST sequence used for protein degradation?
Proline Glutamate Serine Threonine
What is the ubiquitination signal used for protein degradation?
It is a mechanism where cellular proteins are tagged with a small protein called ubiquitin.
What happens to cellular proteins that are tagged with ubiquitin?
They enter a special organelle called a proteasome and the protein will be degraded.
Are enzymes destroyed by ubiquitination?
Yes.
Enzymes such HMG-CoA are de-activated by ubiquitination.
What are the macronutrients that make up our diet?
Carbohydrates.
Proteins.
Fats.
What is the caloric contribution of each of the macronutrients from the diet?
Carbs. 4 kcal/gram.
Protein. 4 kcal/gram.
Fat. 9 kcal/gram.
Alcohol. 7 kcal/gram.
What micronutrients are consumed in the diet?
Essential fatty acids.
Essential amino acids.
Vitamins.
Minerals.
What % of the diet do carbs, fats and proteins make up in a standard diet?
Carbs. 50%.
Proteins. 20%.
Fats. 10%.
What molecules make up carbohydrates?
Polysaccharides. (Starch).
Disaccharides. (Sucrose and lactose).
Monosaccharides. (Glucose, fructose, galactose).
What molecules make up proteins?
Proteins.
Amino acids.
What molecules make up fats?
Triacylglycerol.
Fatty acids (90%).
Phospholipids.
Cholesterol.
What are the major catabolic pathways that involve carbohydrates?
Glycolysis.
Pyruvate dehydrogenase.
TCA cycle.
What are the major catabolic pathways that involve fats?
Beta oxidation.
How much energy will the body take from food?
It will take all the energy it needs and will store the rest.
What forms will the body use to store energy?
Fats.
Glycogen.
Proteins.
What happens to the fats glycogen and proteins that are stored in the body?
They are stored until their energy needs to be released.
How much fat does the average human body have and how much energy does the body store in fat?
15 Kg of stored fat = 135,000 Kcal.
How much protein does the average human body have and how much energy does the body store as protein?
6 Kg of stored protein = 24,000 Kcal.
How much glycogen does the average human body have and how much energy does the body store as glycogen?
0.2 Kg of stored glycogen = 800 Kcal.
Which stored form of energy can be created straight to energy?
Fats can be converted directly to energy via beta oxidation.
What must glycogen and amino acids be converted to before they can give energy?
Protein must be converted to amino acids.
Glycogen must be converted to glucose.
What is the glucose that is made in the fasting state used to power?
Certain tissues that cannot run on fatty acids such as the brain and red blood cells.
Will nitrogen containing molecules ever be stored in the body?
Nitrogen containing molecules will never be stored in the body.
What are excess amino acids used for?
For protein synthesis, energy or specialised products.
What is the protein input and output in an adult?
The input of proteins is equal to the output of proteins.
Will any humans have a positive nitrogen balance?
Children have a positive nitrogen balance as they take in more than they excrete.
Why do children need to eat more nitrogen than they excrete?
Because of the increased protein synthesis that is involved in growth.
What is a negative nitrogen balance usually caused by?
A larger output than input.
A negative nitrogen balance is usually caused by what?
Trauma which causes stress hormones to degrade amino acids in muscle leading to a loss of nitrogen.
Or by inadequate consumption dietary protein.
What is the worst type of negative nitrogen balance?
The lack of an essential amino acid.
What will the lack of an essential amino acid result in?
If 1 essential amino acid is missing then a protein cannot be synthesised.
What will diets that are low in protein result in?
A deficiency of essential amino acids which results in a breakdown of tissue protein.
What will a long term low protein diet cause?
Kwashiorkor syndrome.
What are the symptoms of Kwashikor syndrome?
The distended belly that is seen in famine victims.
What effects does Kwashikor syndrome have on the body?
The body cannot recycle its proteins so it will begin to excrete them leading to loss of muscle.
How does the body deal with amino acids that are obtained in a high protein diet?
The ammonia is removed and excreted.
The carbon skeleton is stored as fat or converted to glucose.
What enzyme will break down proteins in the stomach?
A protease enzyme called pepsin.
What does pepsin break proteins down to?
To form smaller peptides and amino acids.
What must happen to large proteins before they can be broken down?
They must be hydrolysed.
Does the digestion of proteins occur in the small intestine?
Yes.
How do the enzymes that break down proteins in the small intestine enter the small intestine?
As zymogens.
Where are the zymogens that are secreted into the small intestine made?
In the pancreas.
What are the active enzymes that break down proteins called?
Trypsin and chymotrypsin.
What enzyme found in in the intestinal mucosal cells will also help to break down proteins?
An enzyme called amino-peptidase.
How is trypsin activated from its zymogen form of trypsinogen?
Enteropeptidase cleaves trypsinogen to form trypsin
What process is used to activate trypsin from trypsinogen?
Proteolytic cleavage.
What is responsible for activating all of the zymogens other than trypsin?
Trypsin perform proteolytic cleavage on the other zymogens to activate them.
What is the zymogen pepsinogen activated to?
Pepsin.
What is the zymogen chymotrypsinogen activated to?
Chymotrypsin.
What is the zymogen proelastase activated to?
Elastase.
What is the zymogen procarboxypeptidases activated to?
Carboxypeptidases.
What do proteins form once they have been broken down in the small intestine?
Free amino acids or dipeptides.
What parts of a digested protein will cross into the intestinal epithelial cell?
Free amino acids and dipeptides.
What happens to dipeptides once they enter the intestinal epithelial cell?
They are cleaved to amino acids by amino peptidase.
What happens to the individual amino acids once they enter the intestinal mucosal cell?
They enter the bloodstream.
What is the only component of dietary proteins that enters the bloodstream?
The individual amino acids.
Where are the individual amino acids that enter the bloodstream taken to?
The liver.
What happens to the amino acids in the blood once they reach the liver?
They are metabolised or are released back into circulation.
What must amino acids form so that they can be used for energy?
Either a carbon skeleton or a keto-acid.
The formation of a carbon skeleton or keto acid from an amino acid involves the removal of what from the amino acid?
The removal of the amino group from the amino acid.
What is the amino group replaced with when it is removed to form a keto acid?
A ketone group.
Does every amino acid have a corresponding keto acid that can be derived from it?
Yes.
The keto acid of what amino acid will always give a pyruvate molecule?
The keto acid of alanine will always give a pyruvate molecule.
The keto acid of alanine can be used in what glucose making process?
Gluconeogenesis.
If an amino acid is to be catabolised what must it be converted to?
A keto-acid.
What is the process of converting an amino acid to a keto-acid called?
Transamination.
What are the usual products of transamination?
An alpha keto-acid and glutamate.
What can the glutamate that is made via transamination be used for?
It can donate its amino group to the synthesis of new amino acids or it can be oxidatively deaminated.
What kind of molecules carry out transamination?
Transaminases.
The transfer of the amino group to new amino acids is carried out by what molecules?
Aminotranferases.
Which amino acids can take part in transamination?
All amino acids except lysine and threonine.
What enzymes are involved in the transamination of alanine and aspartate are called?
Alanine transaminase (AST).
Aspartate amino transferase (ALT).
Is the term transaminase and transferase synonymous with each other?
Yes.
What happens when a transamination reaction is carried out?
The amino group is transferred from an amino acid to an acceptor keto acid.
Are transamination reactions always reversible?
Yes.
What coenzyme does transamination always need?
Vitamin B6.
What is alanine transaminase abbreviated to?
ALT.
What is alanine transaminase also known as?
Glutamate-pyruvate transaminase.
Where in the body is ALT found in high concentrations?
In the liver.
What reaction is catalysed by alanine transaminase?
The transfer of the amino group from alanine to alpha keto-gluterate to form pyruvate and glutamate.
What amino acid is said to collect nitrogen from other amino acids?
Glutamate.
What do many amino acids use as a keto acid in their transaminase reactions?
Alpha-ketogluterate.
What does alanine transaminase use as a coenzyme?
Vitamin B6.
Is the transamination of alanine to pyruvate reversible?
Yes.
Will ALT work with any other amino acids other than alanine?
No.
Alanine + alpha-ketogluterate and ALT gives what?
L-glutamate + pyruvate.
What is AST also known as?
Glutamate oxaloacetate transaminase.
Where in the body is AST found?
In high concentrations in a variety of tissues as well as in high concentrations in the liver.
What reaction does AST catalyse?
The donation of the amino group from glutamate to AKG to form aspartate and oxaloacetate.
What transaminase reaction is the exception where AKG is converted to form glutamate?
The aspartate transaminase reaction.
What coenzyme does the aspartate transaminase reaction use?
Vitamin B6.
Is the formation of aspartate and oxaloacetate by aspartate transaminase reversible?
Yes.
What cycle can the aspartate formed by the aspartate transaminase reaction enter?
The urea cycle.
Glutamate + alpha-ketogluterate and AST gives what?
Aspartate + oxaloacetate.
What does the donation of amino groups from various amino acids to AKG form?
A surplus of glutamate.
What must happen to the surplus of glutamate that is formed by the transamination of amino acids?
It is oxidatively deaminated.
What is the process of oxidative de-amination?
A process where the nitrogen is removed from glutamate by an enzyme called glutamate dehydrogenase.
Where is glutamate dehydrogenase found?
In the mitochondria.
What does the removal of ammonia from glutamate form?
It will re-form alpha keto gluterate.
What can metabolic process can alpha keto gluterate be used in?
The TCA cycle.
What co-enzyme does glutamate dehydrogenase require to convert glutamate to AKG and ammonia?
NAD+ or NADP+ which will be reduced to NADH or NADPH.
Is the reaction that is catalysed by glutamate dehydrogenase reversible?
Yes.
This means that glutamate can be synthesised this way.
What is the process of the synthesis of glutamate from oxaloacetate and ammonia called?
Reductive amination.
Is the synthesis of ammonia by glutamate dehydrogenase the only way that ammonia can be synthesised?
No.
Does oxidative amination add or remove ammonia?
It removes ammonia to from oxaloacetate and ammonia.
Does reducttive amination add or remove ammonia?
It adds ammonia to form glutamate.
What coenzymes doe glutamate dehydrogenase require?
NAD+ or NADP+.
What is the breakdown of glutamate activated by?
Low energy molecules (ADP/GDP).
What is the synthesis of glutamate activated by?
High energy molecules (ATP/GTP).
Most of the amino acids in the body are what kind of stereo isomer of amino acids?
L-amino acids.
What is the steroisomer of the L amino acid?
The D-amino acid.
How do D-amino acids sometimes enter the body?
Via the diet.
Are D-amino acids metabolised in the same way as L-amino acids.
No.
What enzyme metabolises D-amino acids?
D-amino acid oxidase.
What co-enzymes does D-amino acid oxidase use?
FAD+ and vitamin B2.
What will D-amino acid oxidase convert a D-amino acid to?
A keto-acid.
Can D-keto acids be formed?
No.
As it is not possible to make a stereoisomer of a keto-acid.
What can the body do with keto acids?
They can be used by the body as energy.
They can undergo transamination to form an L-amino acid.
What is often made from the transamination of amino acids?
Glutamate and aspartate.
What are glutamate and aspartate said to collect during transamination reactions?
Nitrogen.
How can ammonia be removed from glutamate that is formed by transamination?
By glutamate dehydrogenase.
What does the body use the urea cycle for?
To de-toxify ammonia.
What is ammonia packaged into by the urea cycle?
By packaging it into a molecule called urea which is then excreted as urine.
What is the best way that the body has of excreting nitrogen?
The urea cycle.
Where does the urea cycle take place?
In the mitochondria and the cytoplasm of liver cells.
Where does the free ammonia that enters the urea cycle come from?
From the glutamate dehydrogenase step.
From the aspartate transaminase step.
What does urea contain?
1 carbon.
1 oxygen.
2 nitrogens.
Where does the carbon and oxygen in urea come from?
CO2.
What is the only organ that can make urea?
The liver.
What happens to urea once it is synthesised?
It will be transported to the kidneys for excretion.
What step of the urea cycle is the rate limiting step?
Step 1, where carbamyl phosphate is formed.
What organelle does the urea cycle begin in?
The mitochondria.
What happens in step 1 of the urea cycle?
Ammonia and CO2, along with 2 ATP molecules will form carbamyl phosphate.
What enzyme is used in step 1 of the urea cycle?
Carbamyl phosphate synthase-1 (CPS-1).
What is the allosteric activator of CPS-1 in step 1 of the urea cycle?
N-acetyl glutamate.
Will CPS-1 work without its allosteric activator in step 1 of the urea cycle?
No.
The synthesis of N-acetyl glutamate is increased by what?
A protein rich meal containing lots of glutamate and arginine.
What amino acids will stimulate the synthesis of N-acetyl glutamate which is the allosteric regulator of CPS-1 in the urea cycle?
Arginine.
Glutamate.
What is the substrate for CPS-1 in step 1 of the urea cycle?
CO2 and ammonia.
What is the product for CPS-1 in step 1 of the urea cycle?
Carbamyl phosphate.
What coenzymes does CPS-1 use in step 1 of the urea cycle?
2 ATP molecules.
What is CPS-1 activated by in step 1 of the urea cycle?
N-acetyl glutamate (allosteric).
What happens in step 2 of the urea cycle, once carbamyl phosphate is formed?
Carbamyl phosphate will combine with an amino acid called ornithine.
What is the product of step 2 of the urea cycle?
Citrulline.
What enzyme is used in step 2 of the urea cycle?
Ornithine transcarbamoylase.
What product of the urea cycle is transported out of the mitochondria?
Citrulline.
What happens in step 3 of the urea cycle once citrulline has been transported into the cytoplasm?
An aspartate molecule combines with citrulline to form arginiosuccinate.
What enzyme is used in step 3 of the urea cycle?
Arginiosuccinate synthase.
Where do the 2 nitrogen atoms on arginiosuccinate come from?
1 from ammonia and 1 from aspartate.
What co-enzymes are used by arginiosuccinate synthase?
1 ATP molecule.
What is the product of step 3 of the urea cycle?
Arginiosuccinate.
What happens in step 4 of the urea cycle once arginiosuccinate has been formed?
Arginiosuccinate is broken down to fumarate and the amino acid arginine.
What enzymes is used in step 4 of the urea cycle?
Arginiosuccinate lyase.
Where are the 2 nitrogen molecules located on arginine?
On carbon 1 so they can be removed together to form urea.
How is arginine made in the body?
Via step 4 of the urea cycle.
What can the fumarate formed in step 4 of the urea cycle be used for?
The fumarate that is produced is a carbon skeleton that can be converted to a number of products such as glucose or aspartate.
What is the substrate used in step 4 of the urea cycle?
Arginiosuccinate.
What is the product formed in step 4 of the urea cycle?
Arginine and fumarate.
What happens in step 5 of the urea cycle once arginine and fumarate have been formed?
The 2 nitrogens are removed from carbon 1 of arginine as ammonia and an oxygen is added to this to form urea.
Are the steps of the urea cycle reversible or irreversible?
Irreversible.
What enzyme is used in step 5 of the urea cycle?
Arginase.
What is the substrate in step 5 of the urea cycle?
Arginine.
What is the product in step 5 of the urea cycle?
Urea and ornithine.
What happens to the ornithine that is formed in step 5 of the urea cycle?
It can go back into the mitochondria and re-enter the urea cycle.
What enzymes of the urea cycle are found in the mitochondria?
Carbamyl phosphate synthase-1 (rate limiting enzyme).
Ornithine transcarbamoylase.
What enzymes of the urea cycle are found in the cytoplasm?
Arginiosuccinate synthase.
Arginiosuccinate lyase.
Arginase.
What happens to the urea that is produced in the liver?
It will be transported to the kidneys where it is excreted in urine.
How can kidney failure affect the urea cycle?
Kidney failure can result in the inability to excrete urea and this causes hyperammonemia.
What 3 factors regulate the urea cycle?
Regulation of CPS-1 by N acetylglutamate.
Substrate concentration.
The induction of enzymes involved in the urea cycle.
What is the substrate for the urea cycle?
NH4+.
What will lead to an increase of the enzymes in the urea cycle?
They will increase with protein metabolism.
Can ammonia be be formed by many processes in the body?
Yes.
What are 5 other processes that can form ammonia in the body?
Glutamine via renal glutaminase.
Glutamine via the intestinal mucosal cells.
Bacterial action in the intestine.
Amines from the diet and degradation of neurotransmitters.
The catabolism of purines and pyrimidines.
What is the most common way that ammonia is transported through the body?
As urea.
Urea is used to transport ammonia from where to where?
From the liver to the kidney.
How is ammonia from peripheral sources tranported through the body?
It will be transported as glutamine.
What enzyme will catalyse the synthesis of glutamine from peripheral ammonia?
Glutamine synthetase.
What coenzymes does glutamine synthetase use to make glutamine?
ATP.
Glutamine synthetase will mainly form glutamine from ammonia in what tissues?
Peripheral tissues such as the muscle, the liver and the brain.
When will glutamine be removed from the bloodstream?
If glutamine has a higher plasma concentration than other amino acids.
What enzyme will remove glutamine from the bloodstream?
Glutaminase.
Where is the enzyme glutaminase found?
In the kidney and the liver.
What will glutaminase convert glutamine to?
To ammonia which is excreted and glutamate is re-formed.
What happens to ammonia formed by glutaminase in the liver?
It is transported to the kidney and excreted.
What is hyperammonemia caused by?
An inability to remove ammonia from the body.
What are the symptoms of hyperammonemia?
Tremors.
Slurring of speech.
Blurred vision.
Coma followed by death.
How can hyperammonemia be acquired?
Through alcoholism, hepatitis or biliary obstruction.
What causes hereditary hyperammonemia?
Genetic defects in any of the 6 enzymes that are involved in the urea cycle.
What symptoms does hereditary hyperammonemia have?
Mental retardation and hyperammonemia in the 1st week of birth.
What causes type 2 hyperammonemia?
A deficiency in orthinine transcarbamoylase.
How can hyperammonemia be treated?
Low protein diet.
Lactulose.
Neomycin.
What is Reyes syndrome?
A condition that primarily occurs in children who have chickenpox or influenza and are given salicylates.
This condition affects the mitochondria and will disrupt the urea cycle.
What characterises Reyes syndrome?
High levels of transaminase in the blood.
What reactions in the body incorporate ammonia?
Glutamate dehydrogenase.
Glutamine synthetase.
Carbamoyl phosphatase synthetase-1.
Where does the urea cycle take place?
Only in the liver.
