Protein Metabolism Flashcards
What are the groups in an amino acid?
- amino group NH2
- side chain R
- carboxyl group COOH
What is the general formula of an amino acid?
2HN - CHR - COOH
What is amino acid metabolism?
The process by which the body breaks down amino acids, the building blocks of proteins, and converts them into other important molecules
Why is nitrogen important in amino acid metabolism?
- nitrogen is a key component of amino acids
- which are the building blocks of proteins
- & the nitrogen source for many other important molecules, including nucleotides and neurotransmitters
How is amino acid biosynthesis connected with nutrition?
Amino acid biosynthesis is intimately connected with nutrition, as the body needs to obtain the necessary raw materials and energy to produce amino acids.
How do certain organisms convert nitrogen gas into ammonia?
Certain organisms, such as bacteria that live in the root nodules of yellow clover, can convert nitrogen gas into ammonia (NH3), which can then be used to synthesize, first, glutamate and then other amino acids.
What is the source of nitrogen for all amino acids?
Nitrogen in the form of ammonia is the source of nitrogen for all amino acids.
Where do the carbon backbones for amino acids come from?
- glycolytic pathway
- the pentose phosphate pathway
- the citric acid cycle
Can all microorganisms synthesize the basic set of 20 amino acids?
Most microorganisms, such as E. coli, can synthesize the entire basic set of 20 amino acids
How many amino acids can human beings synthesize?
Human beings can only synthesize 11 of the 20 amino acids
What are essential amino acids?
The amino acids that must be supplied in the diet are called essential amino acids
What are nonessential amino acids?
The amino acids that can be synthesized if dietary content is insufficient are termed nonessential amino acids
Where does most of the amino acids come from in the body?
Dietary proteins
Describe the amino acid pool
slide 5
What is transamination?
- an amino group is transferred from an amino acid to an alpha-keto acid
- resulting in the formation of a new amino acid and a new alpha-keto acid
Where are aminotransferases active?
Aminotransferases are active in both cytoplasm and mitochondria
What acts as an amino group receptor in all transamination reactions?
α-ketoglutarate acts as an amino group receptor in all transamination reactions
What are some examples of aminotransferases?
Examples of aminotransferases include:
- alanine aminotransferase (ALT)
- glutamate pyruvate transaminase (GPT)
- aspartate aminotransferase (AST)
What is the active form of vitamin B6 used as a coenzyme in transamination reactions?
Pyridoxal phosphate (PLP)
What is the role of α-ketoglutarate in transamination reactions?
- α-ketoglutarate acts as an amino group receptor,
- forming a new α-keto acid & a new amino acid
Can α-ketoglutarate be used to reverse the transamination reaction?
Yes, α-ketoglutarate can be used to reverse the transamination reaction, adding an amino group to a keto-acid to form a new non-essential amino acid
How is ALT used as a diagnostic tool?
To measure liver damage
How are the carbon skeletons of amino acids derived?
The carbon skeletons of amino acids are derived from intermediates of the major metabolic pathways, such as:
- glycolysis
- the citric acid cycle
- the pentose phosphate pathway
What are some examples of molecules that are synthesised from amino acids?
- adenine
- cytosine
- sphingosine
- histamine
- thyroxine
- epinephrine
- serotonin
What is ATP?
ATP (adenosine triphosphate) is a molecule that serves as the primary energy carrier in cells
What is the structural feature that is important in ATP?
Phosphoric acid anhydride, or pyrophosphate, linkage
Why is phosphoric acid anhydride linkage an important structural feature in ATP?
- this linkage between the phosphate groups contains a high amount of potential energy
- which can be used to drive cellular processes that require energy
- when the bond is broken, energy is released and ATP is converted to ADP or AMP
What is the role of glutamate in protein metabolism?
Glutamate is central to protein metabolism as it collects the amino group from all metabolised amino acids
What is the role of α-ketoglutarate in transamination reactions?
In transamination reactions, α-ketoglutarate acts as an amino group receptor, forming a new α-keto acid and a new amino acid
How are all amino groups concentrated?
All amino groups are concentrated through glutamate
What is unique about glutamate in terms of oxidative deamination?
Glutamate is the only amino acid to undergo oxidative deamination at a significant rate
What is deamination?
Deamination is the process of removing an amino group (-NH2) from an amino acid, resulting in the formation of a keto-acid
What is the general structure of a keto-acid?
A keto-acid has a:
- carboxylic acid group (-COOH)
- a ketone group (C=O)
What is the name of the group of enzymes responsible for deamination?
Deaminases
What is glutamate dehydrogenase?
Mitochondrial enzyme that catalyzes the deamination of glutamate, resulting in the formation of α-ketoglutarate & ammonia
What type of enzyme is glutamate dehydrogenase?
Metalloenzyme, which means it contains a metal ion as a cofactor. Specifically, it requires zinc (Zn2+) as a cofactor for its activity.
What makes glutamate dehydrogenase unique in terms of its coenzyme usage?
Glutamate dehydrogenase is the only enzyme that can use either NAD+ or NADP+ as a coenzyme
How is the activity of glutamate dehydrogenase regulated?
The activity of glutamate dehydrogenase is regulated allosterically by ATP/ADP ratios. High levels of ATP inhibit the enzyme, while low levels of ATP activate it
Why is glutamate dehydrogenase important for controlling levels of α-ketoglutarate?
Glutamate dehydrogenase catalyzes the deamination of glutamate, which produces α-ketoglutarate. Therefore, the activity of this enzyme can have an impact on the levels of α-ketoglutarate in the cell.
What is the urea cycle?
Series of biochemical reactions that occur primarily in the liver to remove ammonium ions from the body in the form of urea
What happens during deamination in the liver?
An amino group (-NH2) is removed from an amino acid, resulting in the release of ammonia (NH3)
Why is ammonia toxic to the body?
- highly toxic as disrupts the function of cells and tissues
- small increases in ammonia levels can lead to symptoms such as slurred speech, blurred vision, tremors, and even coma or death
Who discovered the urea cycle?
Discovered by Hans Krebs, a German biochemist, in 1932
In which organ does the urea cycle primarily occur?
Liver
When are amino acids catabolized for energy?
- when there are enough amino acids to satisfy amino acid anabolism
- or during starvation - they cannot be stored
What happens to the products of amino acid catabolism?
The products of amino acid catabolism can be used or stored in the form of fatty acids
What is the difference between glucogenic and ketogenic amino acids?
Glucogenic amino acids can be converted into glucose, while ketogenic amino acids can be converted into ketone bodies
- some amino acids can be both glucogenic & ketogenic
What does glucogenic mean?
Can be made into glucose
What does ketogenic mean?
Can be made into ketone bodies
Why can’t ketogenic amino acids be converted into glucose?
The reserves of oxaloacetate are being used for gluconeogenesis (glucose production), not the TCA cycle
What is the table in slide 27?
slide 27
What happens to oxaloacetate in fasting or diabetes?
Oxaloacetate is consumed to form glucose by the gluconeogenic pathway and hence becomes unavailable for condensation with acetyl CoA
Where is acetyl CoA diverted to in fasting or diabetes?
Acetyl CoA is diverted to the formation of acetoacetate and D-3-hydroxybutyrate, and acetone - these are ketone bodies
What are ketone bodies?
Molecules that are produced from acetyl CoA during the breakdown of fatty acids, particularly in situations where glucose is not readily available as an energy source
Why are abnormally high levels of ketone bodies present in the blood of untreated diabetics?
In untreated diabetes, the body cannot properly use glucose as an energy source due to insufficient insulin, leading to increased production of ketone bodies as an alternative energy source
How can the presence of ketone bodies be detected in a person with untreated diabetes?
The odor of acetone may be detected in the breath of a person who has a high level of acetoacetate in the blood
What are Branched Chain Amino Acids (BCAA) important for?
Muscle maintenance
What 3 ways is BCAA used?
- energy source for muscles
- ingredients which are building blocks for muscles
- supports muscle conditions
Give 3 examples of BCAA
- leucine
- isoleuicne
- valine
What is Maple Syrup Urine Disease?
(also known as branched-chain ketoaciduria)
A rare autosomal recessive condition that causes:
- a build-up of branched-chain α-ketoacids in the body
- leading to severe ketoacidosis
When is Maple Syrup Urine Disease often diagnosed?
In infants as part of a screening program
What is the cause of Maple Syrup Urine Disease?
Caused by a mutation in the branched-chain α-ketoacid dehydrogenase complex
What are the symptoms of Maple Syrup Urine Disease?
- lethargy
- poor feeding
- vomiting
- a distinctive sweet odor in the urine & sweat
How is Maple Syrup Urine Disease treated?
Treated with dietary restrictions, including a low-protein diet and supplementation with special formulae.
What are some general neurological signs?
- lethargy
- irritability
- poor feeding
- developmental delay
What are some focal neurological signs of MSUD?
- abnormal movements
- increasing spasticity
- seizures
- coma
- brain damage, which can lead to death within week
What is the significance of the smell of maple syrup in the urine and earwax?
A characteristic sign of Maple Syrup Urine Disease
What is Phenylketonuria?
PKU, is a rare genetic disorder that occurs with a prevalence of 1 in 10,000 births.
What causes Phenylketonuria?
- caused by an absence or deficiency of phenylalanine hydroxylase
- which leads to the accumulation of phenylalanine in all body fluids as it cannot be converted into tyrosine
What are the symptoms of Phenylketonuria?
- low brain weight
- defective myelination
- hyperactive reflexes
- lowered life expectancy
How is Phenylketonuria diagnosed?
Phenylketonuria is diagnosed in infancy using screening programmes
What is the treatment for Phenylketonuria?
The treatment for Phenylketonuria is a low-phenylalanine diet with tyrosine supplements
- aim is to provide just enough phenylalanine to meet the needs for growth & replacement
- tyrosine is an important precursor to neurotransmitters such as dopamine
What is the Glucose-Alanine Cycle?
A metabolic pathway that shuttles amine groups between the liver and skeletal muscle
What is the function of the Glucose-Alanine Cycle?
To convert amino acids, specifically alanine, into glucose in the liver
What is the equation for energy balance in the body?
Energy consumed = Energy expended + Energy stored
What is the minimum blood-glucose concentration that must be maintained even under starvation conditions?
The blood-glucose concentration must be maintained above 2.2 mM
What is the first priority of metabolism in starvation?
To provide sufficient glucose to the brain and other tissues (such as red blood cells) that are absolutely dependent on this fuel
What is the second priority of metabolism in starvation?
To preserve protein
- accomplished by shifting the fuel being used
- from glucose to fatty acids & ketone bodies
