Amino Acid Catabolism Ii(13 Oct)

Amino acid catabolism II

Dr. Mohammad Akram

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Catabolism?

is the set of metabolic pathways that break down molecules into smaller units and release energy.

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Dynamics of Protein And Amino Acid Metabolism Dietary Proteins

Digestion to Amino Acids

Transport in Blood to Cells

Protein Synthesis

Amino Acids

Metabolites

Functional Proteins

Protein Degradation

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Metabolic Classification of the Amino Acids • Essential

and Non-essential

• Glucogenic and Ketogenic

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Non-Essential Amino Acids in Humans  

Not required in diet Can be formed from α -keto acids by transamination and subsequent reactions • Alanine • Glycine • Asparagine • Aspartate • Glutamate • Glutamine

• Proline • Serine • Cysteine (from Met*) • Tyrosine (from Phe*)

* Essential amino acids 5

Essential Amino Acids in Humans  

Required in diet Humans incapable of forming requisite carbon skeleton • Arginine • Histidine • Isoleucine • Leucine • Valine

• Lysine • Methionine • Threonine • Phenylalanine • Tryptophan 6

Glucogenic Amino Acids 

Metabolized to α -ketoglutarate, pyruvate, oxaloacetate, fumarate, or succinyl CoA Phosphoenolpyruvate

• Aspartate • Asparagine • Arginine • Phenylalanine • Tyrosine • Isoleucine

• Methionine • Valine • Glutamine • Glutamate • Proline • Histidine

Glucose • Alanine • Serine • Cysteine • Glycine • Threonine • Tryptophan

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Ketogenic Amino Acids 

Metabolized to acetyl CoA or acetoacetyl CoA Animals cannot convert acetyl CoA or acetoacetyl CoA to pyruvate

• Isoleucine • Leucine * • Lysine * • Threonine

• Tryptophan • Phenylalanine • Tyrosine

* Leucine and lysine are only ketogenic 8

Amino acid catabolism The carbon frames of amino acids are broken down into metabolites that can either be oxidized into CO2 and H2O to generate ATP (Adenosine-triphosphate) , or can be used for gluconeogenesis. The catabolism of amino acids accounts for 10 to 15% of the human body’s energy production. Adenosine-5'-triphosphate (ATP) is a multifunctional nucleotide that plays an important role in cell biology to intracellular energy transfer.

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Catabolism Process (example) Protein Amino acid Acetyl-CoA (acetyl

coenzyme A)

Citric acid Cycle

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Essential Amino acids

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Arginine The catabolism of arginine begins within the context of the urea cycle. It is hydrolyzed to urea and ornithine by arginase. Urea is the major end product of nitrogen metabolism in humans and mammals. The urea cycle or the ornithine cycle describes the conversion reactions of ammonia into urea. Since these reactions occur in the liver, the urea is then transported to the kidneys where it is excreted. The overall urea formation reaction is:

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Valine, Leucine and Isoleucine Catabolism This group of essential amino acids are identified as the branched-chain amino acids. Because this arrangement of carbon atoms cannot be made by humans, these amino acids are an essential element in the diet. 13

Catabolism The catabolism of all three compounds initiates in muscle and yields NADH and FADH2 which can be utilized for ATP generation. The catabolism of all three of these amino acids uses the same enzymes in the first two (NADH) Nicotinamide Adenine Dinucleotide plus Hydrogen steps. (FADH) Flavin adenine dinucleotide 14

Lysine Catabolism Lysine catabolism is unusual in the way that the ε-amino group is transferred to α-ketoglutarate and into the general nitrogen pool. The reaction is a transamination in which the ε-amino group is transferred to the α-keto carbon of α-ketoglutarate forming the metabolite, saccharopine. 15

Histidine Catabolism Histidine catabolism begins with release of the α-amino group catalyzed by histidase, introducing a double bond into the molecule. The end product of histidine catabolism is glutamate, making histidine one of the glucogenic amino acids. 16

Tryptophan Catabolism A number of important side reactions occur during the catabolism of tryptophan on the pathway to acetoacetate. The first enzyme of the catabolic pathway is an iron porphyrin oxygenase that opens the indole ring. The latter enzyme is highly inducible, its concentration rising almost 10-fold on a diet high in tryptophan.

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INDOLE RING

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Thank You

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