Amino Acid Metabolism Flashcards
nitrate assimilation
The reduction of NO3- to NH4+ occurs in plants, fungi and bacteria in a two-step process called nitrate assimilation
nitrogen assimilation
The formation of NH4+ from N2 gas is called nitrogen fixation and is exclusively a prokaryotic process.
Where must animals get their nitrogen?
No nitrogen fixation or assimilation in animals. Therefore, dependent on plants and microorganisms for the synthesis of organic nitrogenous compounds such as amino acids
Where is the largest cache of N in the body?
Nitrogen makes up about 3% of human body
Largest cache of N is in amino acids, largest cache of amino acids is in skeletal muscle
When does amino acid oxidation occur?
When diet is rich in protein and/or when ingested amino acids exceed the body’s need for synthesis.
Also occurs during starvation, uncontrolled diabetes mellitus, or on low-carb diet.
Why does nitrogen need to be excreted?
Need to deal with NH4+ because it is toxic in mammals - causing cerebral edema, coma and death if it builds up to high concentrations in the blood.
What connects the urea cycle and the TCA cycle?
The aspartate-arginosuccinate shunt of the citric acid cycle
FIGURE 18-1 Overview of amino acid catabolism in mammals. The amino groups and the carbon skeleton take separate but interconnected pathways.
What occurs in digestion of protein
Protein causes the release of gastrin which causes parietal cells to secrete HCl and chief cells to secrete pepsinogen, a zymogen. Autocatalytic cleavage of pepsinogen to pepsin under acid conditions begins the process of protein degradation in the stomach
parietal cells
Protein causes the release of gastrin which causes parietal cells to secrete HCl
cheif cells
Protein causes the release of gastrin which causes chief cells to secrete pepsinogen, a zymogen.
How is pepsinogen activated?
(a)Autocatalytic cleavage of pepsinogen to pepsin under acid conditions begins the process of protein degradation in the stomach.
Acute pancreatitis
Acute pancreatitis is a disease where the pancreatic duct is blocked and the proteolytic zymogens are converted to active enzymes that degrade the lining of the pancreas. Very painful!
Where is trypsin released in the body?
Low pH in the intestine causes secretin release into the blood, which causes the pancreas to release HCO3- into stomach. Exocrine cells release proteases like trypsin into pancreatic duct which leads to the small intestine.
What digestive agent is released into the pancreatic duct?
(a)Low pH in the intestine causes secretin release into the blood, which causes the pancreas to release HCO3- into stomach. Exocrine cells release proteases like trypsin into pancreatic duct which leads to the small intestine.
Where are amino acids abosrbed?
In the small intestinal villi by transporters
Where are individual amino groups metabolised
In the liver
How are amino groups transferred to the liver?
Amino groups are shuttled to liver in form of glutamine from most tissue, also from alanine in muscle
What is the ultimate fate of excess amino groups in mammals?
Conversion to urea for excretion
How is excess nitrogen secreted in microbes and bony fishes?
How is excess nitrogen excreted in most terrestrial vertibrates?
How is excess nitrogen excreted in birds and terrestrial reptiles?
What state of oxidation are the carbons of urea and uric acid?
Highly oxidised, so that chemical potential energy is not excreted
how are many amino transferases named?
There are many amino transferases that are named after the donor of the amino group…alanine amino transferase, aspartate amino transferase, etc
How are amino groups from many different amino acids collected in the liver?
As glutamate, a universal amino donor
Enzyme-catalyzed transaminations: In many aminotransferase reactions, α-ketoglutarate is the amino group acceptor. All aminotransferases have pyridoxal phosphate (PLP) as cofactor. Reaction is readily reversible. Happens in Liver.
Where does α-ketogluterate fit into the TCA cycle?
Product of TCA III, reactant of TCA IV
Isocitrate is decarboxylated by isocitrate dehydrogenase to form α-ketogluterate. α-ketogluterate is then decarboxylated again by α-ketogluterate dehydrogenase complex. Both steps generate reduced NADH.
Aminotransferases use what cofactor?
Pyridoxal phosphate is the prosthetic group of aminotransferases. This is the coenzyme form of pyridoxine or vitamin B6. Pyridoxal phosphate (PLP) and its aminated form, pyridoxamine phosphate, are the tightly bound coenzymes of aminotransferases.
_________________, the cofactor of aminotransferases, is bound to its enzyme how?
Pyridoxal phosphate is bound to the enzyme through a Schiff-base (aldimine) linkage to a Lys residue at the active site as well as non-covalent interactions.
glutamate dehydrogenase
In liver, glutamate dehydrogenase catalyzes ammonium production by oxidative deamination in mitochondria. The glutamate dehydrogenase has the unusual capacity to use either NAD+ or NADP+ as the cofactor.
What does glutamate dehydrogenase use as a cofactor
NAD+ or NADP+
Ammonia is transported from tissue in the form of ________, then converted back to ________ in the liver
Ammonia is transported from tissue in the form of glutamine, then converted back to glutamate in the liver
Describe the process of shuttling ammonia from cells to liver in the body
Ammonia is transported from tissue in the form of glutamine, then converted back to glutamate in the liver.
Excess ammonia in tissues is added to glutamate to form glutamine, a process catalyzed by glutamine synthetase.
After transport in the bloodstream, the glutamine enters the liver and NH4+ is liberated in mitochondria by the enzyme glutaminase
Describe the glucose-alanine cycle
Alanine serves as a carrier of ammonia and the carbon skeleton of pyruvate from skeletal muscle to liver. The ammonia is excreted and the pyruvate is used to produce glucose, which is returned to the muscle.
_________ degrade ingested proteins in stomach and small intestine. Most are __________. Individual AA are absorbed
Proteases degrade ingested proteins in stomach and small intestine. Most are zymogens. Individual AA are absorbed
What happens in the early steps of amino acid catabolism?
Early steps of amino acid catabolism separate amino groups from carbon skeleton in transaminase reaction involving pyridoxal phosphate (PLP) that produces α-keto acids
What are the major transporters of amino groups from tissues to the liver?
Glutamate, glutamine and alanine are the major transporters of amino groups from tissues to the liver where glutamate dehydrogenase or glutaminase liberates the free ammonium ion
Glutamate as an amino group transporter
Most of amino acids are degraded in liver. The first of step of the degradation is to transfer the α-amino group to α-ketoglutarate through transamination. The reaction generates corresponding α-keto acids and glutamate. Glutamate dehydrogenase in liver mitochondria removes α-amino group from glutamate, releases ammonia and regenerates α-ketoglutarate.
Glutamine as an amino group transporter
Ammonia in the blood and throughout the body is detoxified by being conjugated to glutamate by glutamine synthetase to generate glutamine. Glutamine will be degraded by glutaminase in the mitochondria of liver cell into glutamate and ammonia.
Alanine as an amino group transporter
In muscle cells during exercise or fasting, pyruvate from glycolysis accepts amino groups from other amino acids and generates alanine as well as corresponding α-keto acids. These α-keto acids will be used for energy and alanine will travel through the blood. Alanine will be eventually degraded in the liver through transamination reaction with α-ketoglutarate and this will regenerate pyruvate. Pyruvate can be used to generate glucose which will enter the blood to supply muscle for glycolysis.
The NH4+ removed from glutamine by glutamase in the matrix enters the urea cycle how?
It is added to bicarbonate by carbamoyl phosphate synthase to form carbamoyl phosphate
Where does the second amino group enter the urea cycle?
Enters in the form of aspartate, which is bonded to the citrullyl group of the citrullyl-AMP (citrulline bonded to AMP) intermediate to form arginosuccinate in step IIb
Urea Cycle I
Formation of citrulline from ornithine and carbamoyl phosphate; the citrulline passes into the cytosol
Urea Cycle II
Formation of argininosuccinate through a citrullyl-AMP intermediate (entry of the second amino group).
Urea Cycle III
Formation of arginine from argininosuccinate; this reaction releases fumarate, which enters the citric acid cycle
Urea Cycle IV
Hydrolysis produces urea, which regenerates ornithine.
Through what intermediate does glutamine, glutamate and alanine feed amino groups into the urea cycle?
All lead to carbamoyl phosphate, which is combined with ornithine to form citrulline
How does carbamoyl phosphate synthetase I add ATP, bicarbonate and NH3 together to form carbamoyl phosphate?
The terminal phosphate groups of two molecules of ATP are used to form one molecule of carbamoyl phosphate. In other words, this reaction has two activation steps
carbamoyl phosphate
carbamoyl phosphate structure
oxaloacetate structure
oxaloacetate
fumarate
fumarate structure
ornithine
ornithine structure
argininosuccinate structure
argininosuccinate
Which compounds link the TCA cycle and the urea cycle?
oxaloacetate (gets aminated and enters urea cycle as aspartate, bound to citrulline to form argininosuccinate)
fumarate (leaves urea cycle upon cleavage of argininosuccinate, some enters TCA cycle as fumarate, some converted to malate first)
Describe the energetic cost of urea synthesis
2NH4+ + HCO3 + 3ATP + H2O -> urea + 2ADP + 4Pi + AMP + 2H+
But really uses four high energy bonds since ATP is converted to AMP…
Conversion of oxaloacetate to fumerate (via aspartate) and the regeneration of oxaloacetate produces NADH in the malate dehydrogenase reaction. Each NADH gives 2.5 ATP, thus reducing the cost of urea synthesis.
4 ATP bonds but get 2.5 ATPs back so about 1.5 ATP/urea
Describe the pyridoxal phosphate / pyradoxamine phosphate intermediate on amino transferases
