Amino acid metabolism

Cyclin B
Important in cell cycle regulation Prevent premature initiation of another cell cycle Prominent during metaphase, degraded in anaphase Degradation performed by proteasome Degradation produces peptides and amino acids

 Amino acids can be reused for protein synthesis Amino acids can be further processed so the carbon skeleton can be used as fuels or building blocks The released of amino group is converted to urea for secretion by urea cycle

The urea cycle

Digestion of protein in intestine and degradation of protein within the cell provide steady supply of amino acids Many cellular proteins are degraded and resynthesized in response to changing metabolic demands

Ubiquitin tag proteins for destruction Ubiquitin is highly conserved in eukaryotes

Yeast and human ubiqutin differ at only 3 of 76 residues

Ubiquitine conjugation

A chain of four or more ubiquitine is especially effective in signaling the need for degradation

The 20S proteasome comprises 28 homologous subunits. Some of the beta subunits includes protease active sites.

Ubiqutinated proteins are processed to peptide fragments and amino acids Ubiquitin is removed and recycled The free amino acids can be used for biosynthetic reactions, most notably protein synthesis The amino group in amino acids can be removed and processed to urea, and the carbon skeleton can be used to synthesize carbohydrate or fats, or used as fuels

Amino acids degradation

Alpha amino groups in amino acids are converted to ammonium ions by oxidative deamination of glutamat

Aminotransferases catalyze the transfer of -amino groups from -amino acids to an -keto acid

Aspartate aminotransferase: aspartate + -ketoglutarat oxaloacetate + glutamat Alanine aminotransferase: alanine + -ketoglutarat pyruvate + glutamat

This transamination reactions are reversible, thus can also be used to synthesize amino acids from -ketoacids

In general: transaminases funnel -amino groups from a variety of amino acids to -keto glutarate for conversion to NH4+

Oxidative deamination

Pyridoxal phosphate forms Schiff-base intermediates in amonitransferases

Transamination reaction
amino acid 1 + E-PLP -ketoacid 1 + E-PMP
-ketoacid 2 + E-PMP amino acid 2 + E-PLP
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amino acid 1 + -ketoacid 2 amino acid 2 + -ketoacid 1

Aspartate aminotransferase

Serine and threonine can be directly deaminated without first being transferred to -ketoglutarate

serine pyruvate +NH4+

threonine -ketobutyrate +NH4+

Glucose alanine cycle

The urea cycle

CO2 + NH4+ + 3ATP + aspartate + 2H2O

urea + 2ADP + 2Pi + AMP + PPi + fumarate

Metabolic integration of nitrogen metabolism

Inheritted defect of the urea cycle cause hyperammonemia

Blockage of carbamoyl phosphate synthesys has divastating consequences because there is no alternative pathway for urea synthesys Elevated levels of glutamine, form from NH4+ and glutamate, produce osmotic effects that lead to brain swelling