Amino Acid Metabolism Overview

Amino Acid Metabolism Learning Objectives

• Explain the significance of amino acid oxidation.
• Recognize the reaction steps for ammonia removal and the urea cycle (enzymes, metabolites, chemical changes, flow of carbon and nitrogen).
• Briefly understand the oxidation of carbon skeletons in various amino acids, noting the flow of carbon, nitrogen, and sulfur.
• Explain the significance of amino acid biosynthesis.
• Recognize the reaction steps for ammonia assimilation.
• Briefly understand the biosynthesis of non-essential amino acids, noting the flow of carbon, nitrogen, and sulfur.

Amino Acid Catabolism

• During starvation, amino acids replenish TCA cycle intermediates and serve as gluconeogenesis precursors.
• Organisms with high protein diets can oxidize excess amino acids as fuel.
• Excess amino acids are not stored; they are catabolized (oxidized).
• In animals, amino acids released from proteins are the major nitrogen sources.
• Amino acids differ from carbohydrates and fatty acids in their ability to be oxidized.

Removal of Amino Group from Amino Acids

• Amino acids are broken down to release ammonia (NH3)
• The carbon skeletons are converted into various metabolites, including glucose, acetyl-CoA, and ketone bodies.
• Urea is formed from ammonia to be excreted.

Transamination

• The initial step in the catabolism of most amino acids is transamination.
• A universal amino group acceptor is a-ketoglutarate.
• The reaction results in the formation of glutamate and an a-keto acid.
• The reaction is catalyzed by aminotransferases, often requiring pyridoxal phosphate (PLP).

Oxidative Deamination of Glutamate

• Glutamate dehydrogenase catalyzes the oxidative deamination of glutamate in the mitochondrial matrix.
• Oxidation results in the formation of a-ketoglutarate and ammonia (NH3).
• NAD(P)+ is reduced to NAD(P)H in the process.

Non-liver Tissues

• Glutamine synthetase converts glutamate to glutamine, which is transported in the bloodstream.

Glutamine Transport to Liver

• Glutaminase in the liver mitochondria converts glutamine back to glutamate.
• Oxidative deamination of glutamate releases ammonia (NH3).

Urea in Liver

• Ammonia is converted to urea via the urea cycle.
• This process takes place within the mitochondrial matrix.

The Urea Cycle

• The urea cycle involves several enzymatic steps, converting ammonia and carbon dioxide into urea.
• The urea cycle intermediates are crucial for the cycle to function.
• The cycle involves both mitochondrial and cytosolic processes.

Linkage between Urea Cycle and TCA Cycle

• There are connections between the urea cycle and the citric acid cycle.
• Fumarate, the intermediator, links the two cycles and is used in both (and in the production of amino acids, such as aspartate).

Metabolism of Carbon Skeleton

• The carbon skeleton from amino acids can be converted into various intermediary metabolites.
• These include glucose, acetyl-CoA, and ketone bodies.
• Ammonia is a byproduct.

Oxidation of Carbon Skeletons in Amino Acids

• Glucogenic amino acids are degraded to intermediates in the citric acid cycle (or their precursors).
• Ketogenic amino acids are degraded to acetyl-CoA or acetoacetate .

Specific Amino Acid Oxidation

• Alanine, cysteine, glycine, serine, and threonine are all oxidized to pyruvate.
• Isoleucine, leucine, and valine are transformed into acetyl-CoA or propionyl-CoA.
• Lysine degrades into acetoacetate.

Methionine Metabolism

• Methionine degradation leads to succinyl-CoA via propionyl-CoA.
• The cycle involves the recycling of a methyl group.

Leucine, Valine, Isoleucine

• Branched-chain amino acids are broken down to various intermediates that enter either the citric acid cycle or form acetyl-CoA, acetoacetate, or succinyl-CoA.

Lysine Degradation

• Lysine is degraded to acetoacetate.
• This involves transamination, decarboxylation steps, and the formation of intermediates like α-aminoadipate.

Tryptophan Degradation

• Tryptophan is degraded to acetoacetate and pyruvate,

Phenylalanine and Tyrosine Degradation

• Phenylalanine and tyrosine are degraded into acetoacetate and fumarate.

Phenylketonuria

• Phenylketonuria is a genetic disorder due to a defective phenylalanine hydroxylase.
• Phenylalanine accumulates and leads to the production of harmful metabolites.

Aspartame

• Aspartame is an artificial sweetener.
• It is a dipeptide containing phenylalanine.

Amino Acid Biosynthesis

• The nitrogen cycle involves nitrogen fixation (converting atmospheric N2 to NH3).
• Various bacteria, fungi, and plants use nitrogenase to perform this process
• Plants use the ammonia to make amino acids

Synthesis of Essential and Non-Essential Amino Acids

• List of essential and non-essential amino acids, including their related precursors.

Biosynthesis of Specific Amino Acids

• Describe the pathways for the creation of various amino acids from precursor molecules.
• Specific pathways for proline, arginine, serine, and glycine are described.

Tyrosine Biosynthesis

• Tyrosine synthesis starts from the essential amino acid phenylalanine.

Cysteine Biosynthesis

• Cysteine is synthesized starting from methionine and serine.

This quiz covers the essential concepts of amino acid metabolism, focusing on oxidation, biosynthesis, and catabolism. You'll explore the importance of amino acid processes such as the urea cycle, ammonia removal, and the role of amino acids during starvation. Test your understanding of these key biochemical pathways and their significance.