Nitrogen Metabolism

Amino Acid Catabolism

The first step in amino acid degradation is the removal of the α–NH3 group

Carbon Skeleton Breakdown

After nitrogen removal

Transamination Reaction

Transfer of the −NH3 group from one molecule to another via a transaminase enzyme

ALT Function

Alanine aminotransferase (ALT) transfers amino groups to α-ketoglutarate forming pyruvate and glutamate; excess blood ALT can indicate liver problems

AST Function

Aspartate aminotransferase (AST) transfers amino groups to α-ketoglutarate forming oxaloacetate and glutamate; excess AST may indicate liver injury

Nitrogen Fate in Glutamate

The α-amino group on glutamate can be used for N-containing compound synthesis or transported to the liver via glutamine or alanine

Ammonia Detoxification

Mammals convert toxic NH4+ to urea in the liver for safe excretion; nitrogen from purine catabolism is excreted as uric acid

Urea Cycle Purpose

The urea cycle detoxifies and excretes excess NH4+ from amino acid and pyrimidine breakdown

Urea Cycle Step 1

In mitochondria

Urea Cycle Step 2

Carbamoyl phosphate combines with ornithine to form citrulline

Urea Cycle Step 3

Aspartate is added to citrulline to form argininosuccinate

Urea Cycle Step 4

Argininosuccinate splits into fumarate and arginine

Urea Cycle Step 5

Arginine is hydrolyzed with water to release urea and regenerate ornithine

Negative Nitrogen Balance

Condition where more nitrogen is excreted than consumed in the diet

Negative Nitrogen Balance Cause

Missing essential amino acids trigger increased protein degradation

Nucleotide Structure

Nucleotides consist of a base

Sugar Differences

RNA has ribose (2'-OH)

Purine Bases

Adenine (A) and Guanine (G) are purines with two heterocyclic rings

Pyrimidine Bases

Cytosine (C)

PRPP Function

PRPP (5-PhosphoRibosyl-1-Pyrophosphate) provides the phosphoribose component for nucleotide biosynthesis

Pyrimidine Synthesis

Pyrimidine base is built first from carbamoyl phosphate and aspartate

Purine Synthesis

Purine synthesis starts with PRPP sugar and builds the base on it; NH2 from glutamine is added by PRPP-gln amidotransferase

Deoxynucleotide Synthesis

Ribonucleotide reductase converts ribonucleoside diphosphates to deoxyribonucleoside diphosphates using NADPH

Folic Acid Role

Folic acid is required for methylation of dUMP to TMP via thymidylate synthase; deficiency can cause spina bifida and anencephaly