Amino Acid Metabolism Quiz

Nitrogen Metabolism

• Nitrogen disposal is a key function
• Urea cycle is crucial
• Catabolism of the carbon skeleton is involved
• Nitrogen-containing substances are processed

Amino Acid Metabolism: Disposal of Nitrogen

• Amino acids cannot be stored; excess are catabolized and degraded
• Catabolism of amino acids has two phases.
• Phase 1: removal of the amino group to form ammonia and a-keto acid. This involves transamination and oxidative deamination.
• Amino group is recycled or excreted in urine.
• Phase 2: the carbon skeleton of a-keto acids converted into intermediates for energy production.
• The most important route for nitrogen disposal is urea

The fate of N₂ in different organisms

• Ammonotelic animals: excrete ammonia (fishes, larvae of amphibians)
• Ureotelic animals: excrete urea (most land vertebrates, some sharks)
• Uricotelic animals: excrete uric acid (birds, reptiles)

Digestion of Dietary Proteins

• Dietary proteins are broken down into amino acids by enzymes in the stomach, pancreas, and small intestine.
• Enzymes are involved include pepsin, chymotrypsin, elastase, carboxypeptidases etc.
• The breakdown results in a chain of oligopeptides and amino acids
• Free amino acids and dipeptides are absorbed by epithelial cells
• Dipeptides are hydrolyzed into amino acids in the cytosol.

Overall Nitrogen Metabolism

• Amino acids are precursors of nitrogen-containing compounds.
• Amino acid catabolism is part of nitrogen metabolism in the body.
• Nitrogen (N2) from food is converted to amino acids (a.a) and exits as urea then small amounts of $NH_4^+$

Metabolic fates of amino groups: Transamination and Oxidative deamination

• The first step in amino acid catabolism is the transfer of the amino group to a-ketoglutarate.
• This process is called transamination and is mediated by aminotransferase.
• Transamination funnels amino groups to glutamate.
• Oxidative deamination releases ammonia.

Substrate Specificity of Aminotransferases

• Each aminotransferase is specific for one or few amino acids.
• The acceptor is typically $\alpha$-ketoglutarate.
• The equilibrium constant for transamination reactions is near 1.

Mechanism of action of aminotransferases

• All aminotransferases need pyridoxal phosphate derivatives of vitamin B6.
• All amino acids except threonine and serine participate in transamination.
• The text describes enzyme reactions in detail.

Threonine and Serine Dehydratase Enzyme

• Threonine and serine are amino acids.
• Reactions involving dehydratase enzymes in detail.
• Some reactions involve the use of a pyridoxal phosphate (PLP) intermediate.

Two Important Transferases

• Alanine aminotransferase (ALT) or Glutamate-Pyruvate transferase (GPT): transfers amino group from alanine to produce pyruvate and glutamate.
• Aspartate aminotransferase (AST) or Glutamate-Oxaloacetate transferase (GOT): transfers amino group from glutamate to produce aspartate.

Oxidative Deamination

• Amino groups of many amino acids are collected in the liver in the form of glutamate.
• Glutamate is transported to mitochondria where it undergoes oxidative deamination catalyzed by glutamate dehydrogenase.
• Oxidative deamination produces ammonia.

Transdeamination

• The combined action of aminotransferase and glutamate dehydrogenase is referred to as transdeamination.

Regulation of Oxidative Deamination

• The direction of the reaction depends on the relative concentrations of glutamate, a-ketoglutarate, and ammonia.
• Allosteric regulation plays a role, with ATP and GTP as inhibitors, ADP and GDP as activators.

Oxidative Deamination:

• The enzyme glutamate dehydrogenase is present in the mitochondrial matrix and can use either NAD+ or NADP+ as oxidants.
• Oxidative deamination releases ammonia.
• This happens primarily in the mitochondria of liver and kidney.

Glutamine Transports Ammonia

• Many tissues (brain) produce ammonia from metabolic processes.
• Glutamine transports ammonia in a non-toxic form.
• Glutaminase in the liver and kidneys converts glutamine into glutamate and ammonia.

"Glucose-alanine cycle"

• The cycle connects muscle glycolysis with liver gluconeogenesis.
• Amino acids are degraded in the muscles; the amino groups are collected in the form of glutamate by transamination.
• A-amino group can be transferred to pyruvate by alanine aminotransferase.
• Alanine is reconverted to pyruvate in the cytosol, enters gluconeogenic pathway.

Urea Cycle

• Urea is the major form of nitrogen disposal from amino acids.
• One nitrogen comes from ammonium and the other from aspartate.
• Glutamate is a key intermediate.
• Urea is produced in the liver; transported to kidneys for excretion.

Formation of Carbamoyl Phosphate

• The enzyme carbamoyl phosphate synthetase I has an absolute requirement for N-acetylglutamate as an activator.
• Carbamoyl phosphate synthetase II is for pyrimidine synthesis, independent of N-acetylglutamate.

Overall Stoichiometry of the Urea Cycle

• The reaction summarizing aspects of the urea cycle.

The Citric Acid and Urea Cycles Are Linked

• The citric acid cycle and urea cycle intermediates are connected.
• Fumarate produced by the urea cycle is an intermediate in the Citric acid cycle.

Fate of Urea

• Urea diffuses from liver and transported to the kidneys and excreted into urine or lost in feces.
• Bacterial ureases in the intestine act on urea.

Metabolism of Ammonia

• Ammonia is toxic; the body removes it.
• Sources of ammonia include amino acid catabolism, renal glutaminase activity, bacterial action, and purine/pyrimidine catabolism.

Transport of Ammonia in the Circulation

• Ammonia is continuously produced by tissues.
• It's removed rapidly.
• Urea is the primary pathway for ammonia removal, transported from the liver to kidneys.
• Glutamine provides non-toxic transport of ammonia.

Catabolism of the Branched Chain Amino Acids

• Branched-chain amino acids (BCAAs) are typically metabolized in skeletal muscle.
• Steps in BCAA catabolism include transamination, oxidative decarboxylation, and dehydrogenation.
• A deficiency in the enzyme can cause maple syrup urine disease.

Catabolism Carbon Skeleton Amino Acids

• Amino acids are classified as glucogenic or ketogenic based on their metabolic end products.
• Glucogenic amino acids are converted to glucose precursors, whereas ketogenic amino acids are converted to ketone body precursors.
• The catabolism of 10-15% of energy comes from proteins.

This quiz explores key concepts related to amino acid metabolism, including nitrogen disposal, transamination, and oxidative deamination. Test your knowledge on the functions of aminotransferases and the urea cycle. Perfect for students studying biochemistry.