Protein and nucleic acid metabolism Flashcards
What happens to proteins that are ingested?
They are broken down into their constituent amino acids. The amino acids are key metabolic intermediates and are themselves broken down into the carbon skeleton and amino group. The carbon skeletons feed into fundamental metabolic processes and provide the precursors for hormones and neurotransmitters. The amino group is used in amino acid and nucleic acid synthesis or because the ammonia byproducts are toxic they are removed by the urea cycle.
What are the key aspects of protein metabolism?
The amino acids produced from ingesting proteins travel from the intestine to the liver via the hepatic portal vein. The amino acids and metabolic intermediates are trafficked between the liver, kidneys and muscle. The liver cells play a crucial role in the removal of ammonia for it to then enter the urea cycle. Muscle cells will rely on branched chain amino acids for fuel during metabolic starvation or intense exercise as an alternative to glucose.
What makes an amino acid essential or non-essential?
Essential amino acids are those that the body cannot synthesise by itself and hence they must be acquired through diet. (9/20)
Non-essential amino acids can be synthesised by the body by amino transferases, a type of transaminase. (11/20)
How do amino acids feed into the TCA cycle?
The carbon skeleton of a few amino acids can be used to make pyruvate.
Tryptophan → alanine → pyruvate
Glycine ⇌ serine → pyruvate
Cysteine → pyruvate (all hydrophobic amino acids)
The other amino acids can be used to make other key metabolic intermediates for the TCA cycle.
What are the roles of acidic amino acids in metabolism?
Glutamate and aspartate
- often provide the active site for enzymes as their negative charge at neutral pH can interact with Mg2+ or other ions
- they can form metabolic intermediates and participate in the TCA cycle and nitrogen removal
- Aspartate can form oxaloacetate
- Glutamate can form α ketoglutarate
- glutamate is the most abundant neurotransmitter in the CNS
What is the role of basic amino acids in metabolism?
They carry a positive charge in the R group at neutral pH and are crucial sites of covalent linkage through the epsilon cells (par of islet of Langerhans). They provide crucial metabolic intermediates for the urea cycle.
What is the role of branched chain amino acids in metabolism?
They provide a temporary alternative to fatty acids for fuel for oxidation in muscles during short term starvation.
- The glucose alanine cycle is required to remove the nitrogen from the amino groups
BCAAs are also hydrophobic and play a key structural role in proteins.
Which bases are purine and which are pyrimidine?
Purine: Adenine and guanine
Pyrimidine: Cytosine, thymine and uracil
What are the functions of nucleotides?
Nucleic acids are
- A,G,C,T TP undergoing energy transduction
- substrates for RNA and DNA biosynthesis
- able to be attached to CoA
- metabolic regulators (e.g. AMP acts as an allosteric regulator)
What is the function of muscles in protein metabolism?
- Serves as a reservoir of amino acids.
- The major site of break down of muscle protein
- Uses branched chain amino acids as a fuel source
- Muscles can provide crucial precursors for gluconeogenesis during fasting via the glucose-alanine cycle .
When do muscles rely on glycolysis?
Vigorously working muscles operate nearly anaerobically and rely on glycolysis for energy, which produces pyruvate. The pyruvate can be converted to alanine for transport to liver via the CVS to prevent the build up of lactic acid.
What is transamination?
The process of the transfer of an amino group to a keto acid to form a new amino acid. This makes a carbon skeleton available
How is alanine produced via transamination?
How is pyruvate produced via transamination?
Pyruvate produced via glycolysis accepts an amnio group from glutamate in muscle cells and is converted to alanine. Alanine is neutrally charged and its production from pyruvate prevents lactic acid build up therefore preventing blood pH changes.
α ketoglutarate is given as the result of glutamate losing its amino group and it can be used by muscle cells, if there is enough molecular oxygen, for the TCA cycle.
Alanine can be transported safely to the liver via CVS. Within the liver the reverse of the above happens: alanine donates its amino group α-ketoglutarate converting alanine to pyruvate and α-ketoglutarate to glutamate. Glutamate in the liver will enter the urea cycle.
The enzyme alanine aminotransferase facilitates both reactions. Glutamate is a non-essential amino acid.
How are muscle proteins used for fuel?
The major amino acid in muscle protein is leucine and will it be produced when muscle cells are degraded. Leucine donates its amino group α-ketoglutarate and is converted to α-ketoisocaporate and glutamate via leucine amino transferase.
How is glutamine produced?
By further transamination of glutamate. Glutamine and glutamate are crucial intermediates for many processes.
What are the key amino acids for transporting ammonia/nitrogen around the body?
Alanine
Glutamate
Glutamine
pyruvate ⇌ alanine
α-ketoglutarate ⇌ glutamate > glutamine
These intermediates can feed into different cycles and the body will respond to conditions by altering how much of these feed into which cycle.
What is the glucose alanine cycle?
The regulation of fuel sources for either glycolysis or utilisation of BCAAs as fuels. The resulting ammonium ions are stored in glutamate, alanine or glutamine. Glutamine and alanine are ideal amino acids to be transported via the CVS.
How are amino acids used as precursors for neurohormones/neurotransmitters generally?
The key points of the process are:
Decarboxylation of amino acids
All the decarboxylases have co factor pyridoxal 5’ phosphate (PLP) at their active site and decarboxylation results in the removal of CO2
The precursor amino acids are generally essential amino acids.
How are GABA transmitters made?
Glutamine is taken up into neurons by surrounding cells (e.g. glial cells) and is converted into glutamate by by glutaminase. Glutamate is then decarboxylated into GABA by glutamate decarboxylase before packaged into vesicles and released into the synaptic cleft to be taken up by postsynaptic neurons.
What is the role of tyrosine in neuronal signaling?
Tyrosine is taken up into the neuron and converted to DOPA. DOPA is then converted to dopamine and adrenaline by aromatic amino acid decarboxylases.
What are purines synthesised as?
Ribonucleosides, not as free bases.
What is the first step of purine synthesis
The synthesis of activated PRPP from ribose-5-phosphate receiving 2 phosphates from ATP via PRPP synthetase.
What are the different roles of PRPP?
Purine, pyrimidine and pyridine (NAD/NADP) synthesis
What is the purpose of the pentose pathway?
- to maintain carbon homeostasis in order to provide precursors for nucleotide and amino acid synthesis (produces ribose-5-P from the products of glycolysis)
- to provide reducing molecules for anabolism
- to counter oxidative stress
