Amino acid metabolism Flashcards
Is dietary protein essential?
Function?
Some amino acids are essential
* Amino acids are required as building blocks for
proteins
* Also for ** synthesis of neurotransmitters,** creatine, carnitine, haem, purines and pyrimidines
* They act as a source of blood glucose in fasting and starvation
How does nitrogen balance occur in the body?
Dietary Protein –> Amino acid pool
Creatine, purine, pyrimidine <—-Amino Acid pool <—> body proteins
Amino acid pool —> urea, ammonia
Creatine,purines,pyrimidines ——> uric acid,creatinine
What is protein turnover
- Body proteins contiously degraded to amino acids and re-synthesised
- average turnover in an adult 300g-400g
- Turnover variable
- Most proteins have half lives of several days
- Structural proteins - e.g collagen (most abundant protein) may have half lives of years
- Hormones & Digestive enzymes degraded very rapidly, with half lives of minutes
What is the amino acid pool?
- Free Amino acids
- **low concentration **inside cells or in the blood stream
- mixing and exchange with other free amino acids distributed throughout the body
What are protein requirements
- No ‘storage’ form of protein in the body to replace proteins and other N containing compounds.
- protein is needed in the diet to replace the lost amino acids, and allow for tissue repair
- recommendation: **50 – 70 g **protein per day
- high protein intake in a well-fed individual is wasteful:
surplus amino acids are not stored but are rapidly catabolised and the nitrogen excreted as urea in the urine.
Why do we need amino acids?
Where do we get these amino acids
20 amino acids commonly found as ‘building blocks’ of proteins
Humans can synthesise only 10 amino acids from other intermediates, and rely on dietary sources for the other 10 amino acids
Plants and micro organisms can synthesise all 20 amino acids from NH3 and CO2
What is the nitrogen balance in normal, healthy adults?
In normal healthy adults,
total amount of nitrogen taken in the diet as protein = amount of nitrogen excreted from the body in the form of urea, uric acid, creatinine, & NH4+
N intake = N excretion
What is a Positive Nitrogen Balance?
N intake > N excretion
protein synthesis exceeds the rate of breakdown
When does a postive nitrogen balance occur?
- during normal growth in children
- in convalescence after serious illness
- after immobilisation after an accident
- in pregnancy
What is a negative nitrogen balance?
N intake < N excretion
Examples of when negative nitrogen balance occurs?
- in starvation - little/no protein ingested through diet so have to use own body/muscle protein
- during serious illness,
- In late stages of some cancers,
- in injury (can also include surgery) and trauma. - will go into postitve nitrogen balance in recovery to the injury
Consequences of long term negative nitrogen balance?
- If not corrected and becomes prolonged, there will be **irreversible loss of essential body tissue **
- Will ultimately lead to death.
What is the pathway of protein degradation of most cellular proteins?
For most cellular proteins:
* recognised as ‘old’ or damaged
* removed by the ubiquitin breakdown system
What is the pathway of protein degradation of foreign ‘exogenous’ proteins?
Foreign ‘exogenous’ proteins (for e.g from diet)
* ‘old’ or damaged sub cellular organelles
* taken into vesicles by endocytosis or autophagocytosis
* vesicle fuses with lysosomes,
* proteolytic enzymes degrade proteins into amino acids
What can increase the rate of protein degradation?
- Starvation
- Hormones (usually stress hormones)
e.g.Cortisol increases rates of protein breakdown in muscle
What are amino acids degraded to?
- NH2
- oxo acid (keto acid)
e.g. (Pyruvate)
How are amino acid broken down
- Oxidative deamination
- Transamination - transfer amino group from amino acid to keto acid to produce a new keto acid and amino acid
*
- Remove amino group (NH2)
- deal with carbon skeleton
What occurs to the N of the amino acid?
The N part of the amino acid is removed by transfer to an
acceptor molecule
Describe transamination?
What happens to the NH2?
RELEASE OF NH2 GROUP AS AMMONIA NH3 or NH4+
Describe oxidative deamination?
Describe transamination?
What is the fate of the oxo-acids?
- after losing their amino groups, most of the 20 amino acids become oxo acids
- can be metabolised by the TCA pathway to CO2 and H2O and provide a source of ATP.
What is glucogenic?
in starvation, the carbon skeletons of 13 of the amino acids can also be converted back to glucose, by the liver, and these are classified as ‘glucogenic’.
When are Amino acids ketogenic?
- Leucine and lysine can only be degraded to acetyl CoA and are therefore classified as ‘ketogenic’. cannot be converted into glucose
- Phenylalanine and tyrosine catabolised with part of their chemical structure being converted into glucose
- count as both glucogenic and ketogenic (also tryptophan & isoleucine )
What is the role of the liver in N metabolism?
- removal of amino acids, glucose & fats from the portal blood supply
- absorbed amino acids used for synthesis of cellular proteins
- synthesis of plasma proteins (albumin, clotting factors, lipid transport proteins etc)
- synthesis of haem, purines & pyrimidines for DNA & RNA
- degradation of excess amino acids by transdeamination
- conversion of NH3 to urea for excretion (urea / ornithine cycle)
What is the overview process of amino acid metabolism?
CENTRAL ROLE OF THE LIVER
How are the transport of ‘amino groups’ and ‘ammonia’ to the liver?
- skeletal muscle continuously degrades proteins to amino acids
- the liver is the only organ which can convert the amino groups of these amino acids to urea for excretion from the body
- The amino groups (NH2) are transported as glutamine in the blood stream
Describe glutamine metabolism?
What is the importance of glutamine?
- safe carrier of ammonia in the blood
- Ammonia is toxic to the brain
- Glutamine can carry 2 ammonia equivalents to the liver for urea formation
- Glutamine can deliver ammonium ions to the kidney for pH regulation (buffering H+)
Describe the urea cyle?
Important amino acids in the inter-organ transport of nitrogen
- Alanine
- Glutamate
- Glutamine
- aspartate
What are the end products of nitrogen metabolism?
- UREA - protein breakdown
- CREATININE - creatine phosphate breakdown
- URIC ACID - DNA & RNA breakdown
- AMMONIA (NH4+) - control of body pH
Describe ammonia
- Ammonia is neurotoxic
- Exact mechanism not known
- Cerebral oedema, coma and death
- Seems to involve cell death
What is HYPERAMMONAEMIA?
Impaired conversion of NH3 to urea
LIVER FAILURE
(viral hepatitis, ischaemia, liver cirrhosis,
toxins eg aflatoxin in mouldy peanuts)
GENETIC DEFECTS
reduction in catalytic activity of any enzyme
of the urea cycle
