Amino Acid Metabolism

Protein Degradation

provides a supply of amino acids (not obtained only through diet)

Cellular Proteins

are broken down and resynthesised in response to metabolic demands

Amino Acids

used for synthesis of:

• proteins

• nitrogenous compounds

  • nucleotide bases

  • heme

  • neurotransmitters

Excess Amino Acids

cannot be stored

Glycogen or Fat

what excess amino acids are converted to

Kwashiorkor

a severe form of protein malnutrition

• muscle wasting

• apathy

• lowered levels of albumin

• reduced osmotic pressure in blood, leading to oedema of tissues

Ammonia

source of nitrogen in all amino acids

Carbon Backbones

come from intermediates of metabolism in different pathways

• glycolytic pathway

• pentose phosphate pathway

• citric acid cycle

Glutamate

the gateway amino acid

Nitrogen Fixation

process that reduces N₂ to NH₃

Nitrogenase Complex

consists of:

• reductase

• iron-molybdenum containing nitrogenase

Nitrogenase Complex

nitrogen is fixed by this complex

Reductase

provides electrons with high reducing power

Nitrogenase

uses electrons to reduce N₂ to NH₃

16 ATP Molecules

hydrolyzed to form 2 molecules of ammonia

Ammonia

can be obtained from the reduction of the nitrate ion

Diazotrophic Microorganisms

fix 60% of the earth’s newly fixed nitrogen

Ammonium Ion

assimilated into an amino acid through glutamate and glutamine

Glutamate and Glutamine

act as nitrogen donors for most amino acids

Glutamate

contributes its alpha-amino group by transamination in the synthesis of most amino acids

Glutamine

contributes its side chain nitrogen atom in the synthesis of Trp and His

Glutamate Dehydrogenase

enzyme important for both biosynthesis of glutamate and glutamate breakdown

reversible reaction

Glutamine Synthase

a second ammonium ion is incorporated into glutamate to form glutamine

Ammonium

ammonia generated by nitrogenase complex becomes this ion in aqueous solutions

Reductive Amination

converts a carbonyl group to an amine via an imine intermediate

Tyrosine

sometimes classed as essential

• can be synthesized from available phenylalanine in one step

9

number of essential amino acids

11

number of nonessential amino acids

Alpha Ketoglutarate

converted into glutamate by reductive amination

• catalysed by glutamate dehydrogenase

Aspartate

made from the addition of an amino group to oxaloacetate

Alanine

made from the addition of an amino group to pyruvate

Transamination Reactions

catalysed by aminotransferases

Aminotransferases

sometimes called amino transaminases

• move around amino groups between different amino acids

Aspartate Aminotransferase

catalyses the interconversion of oxaloacetate and glutamate to aspartate and alpha ketoglutarate

Alanine Aminotransferase

interconverts pyruvate and glutamate to alanine and alpha ketoglutarate

Glutamate

always serves as one of the amino acids in aminotransferase reactions

• serves as the gateway between amino groups of most amino acid and free ammonia

Liver Disease

can be detected and diagnosed using aspartate and alanine aminotransferase (AST and ALT)

• hepatic cell injury manifested by elevated serum aminotransferase activity

Protein Turnover

degradation and resynthesis of proteins

Protein Half Lives

range over several orders of magnitude

Removal of Nitrogen

first step in amino acid degradation

Liver

major site of amino acid degradation

Branched Chain Amino Acids

mainly oxidized in skeletal muscle

Alpha Amino Groups

converted into ammonium ions by the oxidative deamination of glutamate in the liver

• alpha amino group transferred to alpha ketoglutarate, yielding glutamate

• glutamate oxidatively deaminated to yield the ammonium ion

Glutamate Dehydrogenase

mitochondrial enzyme that converts the nitrogen atom in glutamate to a free ammonia ion by oxidative deamination

• can use NAD+ or NADP+

Ketamine Hydrolysis

follows dehydrogenation of the C-N bond in oxidative deamination

Urea

excess ammonia ions are converted into this water-soluble, inert and non-toxic molecule

Urea Role

prevents the accumulation of the toxic ammonium ion produced from amino groups

Urea

contains two nitrogens

• one from ammonium ion

• one from aspartate

Glutamate

is key in collecting nitrogen and filtering it towards the urea cycle

• collects nitrogen from amino acids using transamination reactions

• amino acids converted back to glutamate through transamination reactions

• glutamate from catalysis by aspartate aminotransferase

Urea Cycle

takes place in both cytosol and mitochondria of the liver

Citrulline

combines with aspartate (second source of nitrogen, second reaction in urea cycle)

Carbamoyl Phosphate

urea cycle begins with the formation of this

• occurs in the mitochondria

• requires 2 molecules of ATP

Carbamoyl Phosphate Synthetase

catalyses the coupling of ammonia with bicarbonate to form carbamoyl phosphate

High Levels of Ammonium

• disrupt neurotransmitter systems

• impact energy metabolism

• disrupt osmotic balance of the nerve cell and causing cellular swelling

Ammoniotelic Organisms

organisms that release nitrogen as ammonium and rely on the aqueous environment for dilution

Uricotelic Organisms

secrete excess nitrogen as the purine uric acid

Uric Acid

contains 4 nitrogens