Nitrogen metabolism

• Ketogenic amino acids: Amino acids that can be converted into acetyl-CoA, which is the precursor of ketone bodies
• Glucogenic amino acids: Can be converted into glucose through gluconeogenesis
• There are twenty different amino acids in proteins
• Protein turnover

  Proteins are broken down into amino acids to be reassembled into new protein
• Protein turnover varies massively between tissues
• 2% protein turnover for muscle and 15% protein turnover for intestine
• What happens to amino acids that escape resynthesis during protein turnover?

  become oxidised in the tissue or enter the bloodstream
• The liver is the first place that amino acids go from the intestine
• amino acid backbones cannot be interconverted
• amino acid degradation enzymes have a very high Km, meaning that excess amino acids are always degraded
• the branched amino acids are leucine, isoleucine and valine
• The liver preferentially takes the non-branched chain amino acids
• The hepatic portal vein is where blood enters the liver from the intestine
• The muscle uses a lot of branched chain amino acids for energy
• Hypoinsulinemia leads to proteolysis
• The muscle releases all types of amino acids, but disproportionately high amounts of alanine and glutamine
• Muscles use transamination to remove amine groups so that the skeleton can be burnt
• Transamination

  Shuffling amino groups so that carbon backbones can be used for energy and amine groups are channelled to the liver for detoxification
• Main amino group acceptors:

  Pyruvate, Alpha-keto glutarate, Oxaloacetate
• What does pyruvate become when it accepts an amine group?

  alanine
• what does alpha-keto glutarate become when it accepts an amine group?

  glutamate
• What does oxaloacetate become when it accepts an amine group?

  aspartate
• amine group acceptors are derived from common pathways
• amine group acceptors take amino groups to the urea cycle in the liver for detoxification
• what is the carrier of the urea cycle?

  ornithine
• does the urea cycle consume ATP?

  yes
• The urea cycle partially occurs in the mitochondria and partially in the cytoplasm
• Some amino acid skeletons feed into the Krebs Cycle, while others can only be made into acetyl CoA
• All pathways of amino acid synthesis are linked to:

  • Glycolysis
  • Krebs cycle
  • Pentose phosphate pathway
• Essential amino acids cannot be synthesised by humans
• Amino acids based on pyruvate, oxaloacetate, and alpha-ketoglutarate are non-essential amino acids
• When the ribosome is making a protein from mRNA and reaches a codon that it doesn't have the protein for, it will stop synthesising
• Other products from amino acids:

  • Creatine
  • Non-peptide hormones
  • Nucleotides
• Most purine comes from salvage pathways
• We can inhibit enzymes that produce purine to stop rapid multiplication of cancer cells
• to slow down cancer cell multiplication, we can treat with a drug that looks like purine but cannot actually be used to make DNA, therefore blocking the synthesis pathway