Amino acid synthesis and degradation Flashcards
Examples of catabolism in body
Energy yielding nutrients (fats, carbs, proteins) –> energy poor end products (H2O, CO2, NH3)
-gives off chemical energy (ATP, NADPH)
Examples of anabolism in body
Precursor molecules (amino acids, sugars, fatty acids, nitrogenous bases) --> cell macromolecules (proteins, polysaccharides, lipids, nucleic acids) -requires chemical energy (ATP, NADPH)
5 examples of essential amino acids
From diet
- Histidine
- Isoleucine
- Leucine
- Lysine
- Methionine
Non-essential amino acids
Synthesised in body
- Alanine
- Aspargine
- Aspartate
- Glutamate
- Serine
Conditionally essential amino acids
Synthesised in body Not essential except in times of illness and stress -Arginine -Cysteine -Glutamine -Glycine -Proline -Tyrosine
Amino acid synthesis
9 non-essential amino acids are made from glucose + N source (amino acid or ammonia)
Non essential AAs can also be made from essential AAs
-Methionine donates S for cysteine
-Phenylalanine forms tyrosine
Protein digestion
- ingested protein broken down in stomach and small intestine
- proteolytic enzymes (proteases)
- AAs absorbed into epithelial cells and enter blood
- active transport into cells
AAs derived from intermediates of glycolyss
Serine, glycine, cysteine, alanine
AAs related to TCA cycle intermediates
Aspartate - oxaloacetate (reversible) –> Aspargine, Methionine, Threonine, Lysine
α-ketoglutarate –> glutamate –> Glutamine, Proline, Arginine
When does amino acid degradation occur
Excess can neither be stored or excreted
Sources: during normal synthesis and degradation some is no longer needed i.e. when diet exceeds need
Proteins can act as energy source during fasting
Some AAs return to precursors, others not
Define glucogenic degradation
Carbons converted to glucose (some are both)
Define ketogenic degradation
Converted to acetyl CoA or acetoacetate (ketone bodies)
-some are both keto- and glucogenic
Where does AA degradation take place
Liver
Products of AA degradation
Carbon - glucose
CO2
Acetyl CoA
Acetoacetate
What happens to nitrogen after AA degradation
- Removal of α amino gp - transaminases/ amino transferases
- Formation of ammonia
- Urea cycle
Define transamination
Give example
Amino gp from one amino acid transferred to another
- α ketoglutarate and glutamate usually a pair (cofactor is pyridoxyl phosphate, derived from vit. B6)
- reaction is reversible (involved in synthesis and degradation)
Removal of amino acid nitrogen as ammonia
Glutamate can collect nitrogen from other amino acids
This is converted to ammonia by glutamate dehydrogenase in liver mitochondria
Ammonia enters urea cycle
Protein degradation
Proteins continuously synthesised and degraded at different rates
Proteins recycled within cells
Lysosomes
protease filled vesicles
Ubiquitin
Small proteins that target proteins for degradation
Proteasome
Protease complex, protein is unfolded and degraded using ATP
Nitrogen and bio systems
N2 not usable in biological systems
NH3 usable and crosses membranes
NH4+ toxic
What is used by organisms to excrete nitrogen?
Ammonia, uric acid and urea
Nitrogen balance
Nitrogen ingested (dietary proteins) = nitrogen excreted
Nitrogen balance for children, pregnant, disease, starving
Children & pregnant: +N balance
Disease/ starvation: -N balance
Where do the steps of urea cycle take place
First 2 in mitochondrion
Other 3 in cytosol
How does nitrogen enter urea cycle
Enters as NH4+ and aspartate
What initiates the urea cycle
Ornithine, is regenerated afterwards
Control of urea cycle
‘Feed forward’ regulation: higher the rate of ammonia production, higher the rate of urea
Allosteric activation of enzymes (arginine stimulates carbamoyl phosphate synthase)
High protein diet or fasting induces urea cycle enzymes –> frequent urination
Tissues (precise reactions and location depends on physiological state - fed or fasting)
Fasting: muscle protein broken down to AAs
Alanine (from pyruvate in muscles) and glutamine (mops up nitrogen) enter blood
These are broken down to glucose and ketone bodies in liver and used for energy
Ketone bodies when low glucose
Reconverted to acetyl CoA and enter TCA cycle for energy when glucose is low
2 examples of ketone bodies
Acetoacetate, beta hydroxybutyrate
Acetoacetate spontaneously breaks down to acetone
What gives rise to ‘fruity’ smell of breath
Ketotic states (energy coming from ketone bodies)
pH of ketone bodies
Acidic –> can lead to ketoacidosis
Inborn errors of AA metabolism
- deficient enzymes in AA metabolism lead to accumulation of harmful products
- Phenylketonuria: mutation in phenylalanine hydroxylase, mental retardation
- urea cycle disorders: accumulation of ammonia, toxic to NS
Jesse Gelsinger
1981-1999
- urea cycle disorder: ornithine transcarbamylase deficiency
- inability to metabolise ammonia
- first person to die as result of gene therapy clinical trial (adenoviral vector)
