Introduction to Nitrogen Metabolism and Metabolism of Amino Acids Flashcards
Nitrogen can be released by kidney to a smaller amount as ______ or other molecules, but it is mostly released as _______ that is formed only in the liver by the ____________.
Ammonium ions;
Urea;
Urea cycle
Which enzyme converts phenylalanine to tyrosine?
Phenylalanine hydroxylase
Deficiency of which amino acid makes cysteine a dietary essential amino acid?
Methionine
How many grams of amino acids does the amino acid pool contain?
100 g
What are the sources to fill the amino acid pool?
Filled by:
- synthesized nonessential amino acids
- amino acids generated by body protein degradation.
What purposes take out amino acids from the amino acid pool?
- Body protein synthesis
- synthesis of specialized products derived by conversion of amino acids
- eventual degradation for energy metabolism in all cells
- synthesis of glucose or ketone bodies in hepatocytes (glucogenic and ketogenic amino acids)
What are the dietary essential amino acids?
Phenylalanine Valine Tryptophan Threonine Isoleucine Methionine Histidine Arginine Leucine Lysine (PVT TIM HALL)
What is the grouping of the amino acid Arginine?
Semi essential or conditionally non-essential:
- bc it can be sufficiently synthesized in healthy adults, however in individuals with dysfunction of small intestines, kidney, or following trauma, sepsis or burns, it becomes dietary essential.
- also is dietary essential in children.
Deficiency of which amino acid makes tyrosine an essential amino acid?
Phenylalanine
Name three concepts how humans can synthesize non-essential amino acids
- using aminotransferase reactions
- using amidation reactions
- using other amino acids as precursors like for the synthesis of cysteine and tyrosine
What is special in the protein degradation in the ubiquitin-proteasome proteolytic pathway?
ATP-dependent
What is ubiquitin?
Proteins that are meant to be degraded are tagged by binding of the small, globular non-enzymic protein ubiquitin. Several ubiquitins can be added in tandem.
What is a proteasome? What is its action?
The proteasome is a large, barrel-shaped macromolecular complex found in cytosol and degrades mainly endogenous proteins. The proteasome unfolds the protein and cuts it into peptide fragments which are totally degraded by cytosolic nonspecific proteases
Is ubiquitin degraded together with the target protein?
Ubiquitin itself is recycled and is not degraded
What is special in the protein degradation performed in lysosomes?
Lysosomal degradation takes place in lysosomes with acid hydrolases.
This degradation is ATP-independent
What type of proteins do lysosomes mainly degrade?
Extracellular, like plasma proteins or cell-surface membrane proteins
What is the significance of the lysosomal membrane?
Prevents degradation of cytosolic proteins and allows a higher proton concentration inside of lysosomes.
How are dietary amino acids transported into the intestinal mucosal cells?
Amino acids during digestion are transported against a concentration gradient by secondary active co-transport with sodium ions into the intestinal mucosal cell. The primary active transport by sodium-potassium ATPase provides a gradient that allows the transport of amino acids together with sodium ions into the intestinal mucosal cells.
The liver obtains most of the dietary amino acids via the ____________
Portal Vein.
Amino acids that are not used by the liver are released into the _____________, especially the __________.
Blood amino acid pool
Branched chain amino acids (Valine, isoleucine, and leucine)
Only ____________ perform the complete urea cycle to generate urea in the cytosol, which is why _______ from other cells has to be transported to the ________.
Hepatocytes
Nitrogen
Liver
Cells release their nitrogen mainly in the form of _______ or ______ into the blood.
Alanine;
Glutamine
How many amino groups do alanine and glutamine contain when transporting nitrogen to liver?
Alanine – 1 amino group = 1 nitrogen to liver
Glutamine – 1 amino group + 1 amide group = 2 nitrogens to liver
What is the role of the kidney in nitrogen metabolism?
- the kidney excretes mainly urea which contains two nitrogens (formed in the liver, about 12-20 g nitrogen). Urea is the least toxic nitrogen containing molecule in higher concentration
- The degradation of purine nucleotides in intestinal mucosal cells or the liver leads uric acid, which is also released by the kidney
- kidney forms ammonium ions which are released into the urine. This release is adjusted to the amount of protons needed to be excreted in order to maintain normal blood pH.
The free ammonium ions in the kidney are mainly formed by which enzyme?
Glutaminase (cleaves glutamine to glutamate)
What is the role of glutamate dehydrogenase in the kidney?
glutamate dehydrogenase can use the formed glutamate and generates another free ammonium ion and alpha-ketoglutarate
A high creatinine level in blood and a low level in the urine can indicate what?
Kidney malfunction
Which transporter is defective in patients with cystinuria?
transporter COAL is deficient
The transporter COAL is needed for what?
transport of cystine, and the dibasic amino acids ornithine, arginine and lysine.
Cystine is formed from ___________ that are linked to each other via _________.
2 cysteines;
Disulfide bond
Cystine is found in ______ and ______ and it is NOT very _______.
Tissues;
Blood;
Water-soluble
What is the most common genetic defect of amino acid metabolism?
Cystinuria
A patient comes to you with the formation of calculi which block the urinary tract and by the increase of cystine, ornithine, arginine and lysine in the urine. This patient has what?
Cystinuria
Cystinuria is characterized by an increase of which amino acids in the urine?
Cystine
Ornithine
Arginine
Lysine
What Is Hartnup disease?
Defect in the transport of neutral amino acids, like dietary essential tryptophan.
_______ can be used for the synthesis of _________. This is a minor pathway, but low levels of this amino acid can lead to pellagra-like symptoms.
Tryptophan;
Niacin;
Tryptophan
In most cases, the first step of amino acid degradation is ___________ by __________, which is followed by eventual degradation of the ___________ in the ________.
- Removal of nitrogen
- Transamination
- Carbon skeleton
- TCA cycle
_______________does not generate free ammonium ions which can be toxic. It transfers the nitrogen from the -amino group to the respective -ketoacid and verse visa.
Transamination
What occurs in a transamination reaction?
Nitrogen is transfered from the alpha-amino group to the respective alpha-ketoacid and vice versa
What is mainly performed in the liver and kidneys that generates free amonia to be used for the urea cycle or released into the urine?
Deamination
What catalyzes irreversible reactions and generates free ammonium ions from the side chains of certain amino acids?
Glutaminase
Arsparaginase
What is so special about Glutamate dehydrogenase?
- Deamination
- alpha-amino group nitrogen of glutamate is released as free ammonium ion. This reaction is reversible and this enzyme can also be used to scavenge free ammonium ions and synthesize glutamate.
Glutamate, via transamination, can be used to form what?
Alpha-ketoglutarate
Aspartate, via transamination, can be used to form what?
Oxaloacetate
What amino acid is used to form pyruvate by transamination
Alanine
Note: Glutamate is also formed in this rxn
What is the general reaction catalyzed by aminotransferases?
A reversible reaction which always needs two substrates, an alpha-amino acid and an alpha-ketoacid (and they form as products the respective alpha-ketoacid and alpha-amino acid.)
What coenzyme is needed for aminotransferases?
Pridoxal-phosphate (PLP) aka Vit B6
Why is it that in most aminotransferase reactions, glutamate is either formed or used?
Alpha-ketoglutarate is the amino acceptor
What is the reaction catalyzed by ALT?
Alanine aminotransferase uses alanine and alpha-ketoglutarate as substrates and forms pyruvate and glutamate
What is the reaction catalyzed by AST?
Aspartate aminotransferase uses aspartate and alpha-ketoglutarate and forms oxaloacetate and glutamate.
What is the reaction catalyzed by ALT important for and why?
This reversible reaction is important for the alanine-glucose cycle, where in the muscle alanine is formed and released into the blood and in the liver alanine is used to forms pyruvate
_______ is found in high concentrations in cytosol of hepatocytes and it is used as ____________when it accumulates in serum
ALT
liver injury marker
_______ is found in cytosol and in mitochondria, in serum it can also be used as ____________together with __________.
AST
liver injury marker
ALT and other injury markers
The alpha-ketoacid for alanine is
pyruvate
The alpha-ketoacid for aspartate is
oxaloacetate
The alpha-ketoacid for glutamate is
alpha-ketoglutarate
What is the concept of grouping amino acids into glucogenic amino acids and into ketogenic amino acids?
A glucogenic amino acid leads to a degradation product that can be used for gluconeogenesis. This is for example pyruvate or an additional molecule in the TCA cycle.
A ketogenic amino acid leads to acetoacetyl CoA or acetyl CoA. These carbons cannot be used for gluconeogenesis but they can be used for ketone body synthesis in the liver.
Which two amino acids are purely ketogenic?
leucine and lysine
What is an example of an amino acid that can be both glucogenic and ketogenic?
Tryptophan
Degradation of which specific amino acids eventually enter the TCA cycle as alpha-ketoglutarate?
Glutamate
Proline
Histidine
Arginine
Degradation of which specific amino acids eventually enter the TCA cycle as succinyl CoA
Isoleucine
Valine
Methionine
Threonine
Degradation of which specific amino acids eventually enter the TCA cycle as Fumarate?
Phenylalanine
Tyrosine
Degradation of which specific amino acids eventually enter the TCA cycle as oxaloacetate?
Asparagine (Asn) Aspartic acid (Asp)
Which glucogenic amino acids are degrated to pyruvate?
Alanine (Ala) Cysteine (Cys) Glycine (Gly) Serine (Ser) Threonine (Thr) Tryptophan (Trp)
Amino acids leading to acetyl CoA or acetoacetate are
Isoleucine (Ile) Phenylalanine (Phe) Tryptophan (Trp) Tyrosine (Tyr) Leucine Lysine
Related to synthesis, how is glutamine formed from glutamate?
Synthesis: glutamate and free ammonium ions are used to form glutamine catalyzed by glutamine synthetase using ATP. This reaction is especially important in brain metabolism as ammonium ions are highly toxic for the brain.
Related to synthesis, how is asparagine formed from aspartate?
Synthesis: Aspartate and glutamine are used to form asparagine [not from free ammonium ions]
- Which TCA cycle intermediate is formed in the degradation starting with asparagine?
Asparagine is deaminated to aspartate by asparaginase.
Aspartate transamination generates oxaloacetate (TCA cycle)
Which three human enzymes can use free ammonium ions for synthesis?
- Glutamine synthetase
- Glutamate dehydrogenase
- carbamoyl phosphate synthetase I in hepatic mitochondria uses carbon dioxide and free ammonium ions
What is special about the reaction catalyzed by glutamate dehydrogenase?
Glutamate dehydrogenase catalyses a reversible reaction and uses alpha- ketoglutarate and free ammonium ions and NADPH when it is used for glutamate synthesis. Glutamate can then be used for amino acid synthesis using the respective alpha-ketoacid of the wanted amino acid.
This enzyme DOES NOT use PLP as cofactor, it uses very likely NADPH when it synthesizes glutamate and it used NAD+ when it degrades glutamate to alpha-ketoglutarate and ammonium ions.
This means that glutamate dehydrogenase is also able to oxidatively deaminate glutamate and this enzyme can form free ammonium ions for the urea cycle in the liver or for release into the urine in the kidney
