What do amino acids and nucleotides contain that carbohydrates and fats don’t? Where does it come from?
.Nitrogen
Air contains approx 80% nitrogen; do we breathe it in? No, we get it from our diet
Nitrogen metabolism
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Constant Protein Turnover:
Some proteins (e.g., structural proteins) are stable and last days, weeks, or even months.
Other proteins (e.g., cell cycle proteins) have a short half-life, measured in minutes.
Need for Replacement:
All proteins are eventually "turned over," necessitating their replacement.
Amino Acid Sources:
New proteins require amino acids from the diet.
Dietary protein is digested into amino acids for anabolic pathways.
No Storage for Excess Protein:
Unlike sugars and fats, the body cannot store excess protein.
Surplus protein must be catabolized.
Dietary Proteins are EnzymaticallyHydrolyzed
.What are the key enzymes involved in protein digestion, and where do they act in the digestive system?
Pepsin: Cuts proteins into peptides in the stomach.
Trypsin and Chymotrypsin: Break down proteins and larger peptides into smaller peptides in the small intestine.
Aminopeptidase and Carboxypeptidases A and B: Degrade peptides into amino acids in the small intestine.
Enzymatic Degradation of Dietary Proteins
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Role of dietary protein in overall nitrogen metabolism
.Animal proteins mostly contain all the essential amino acids but many plant proteins are deficient in some so that is why vegetarians need to have a wide variety of different plant foods to ensure adequate intake of essential a/a
Primary role of carbs and fat? - To provide energy
Primary role of amino acids? - Building blocks for proteins
20 coded a/a: 11 are “non-essential” (can be synthesised in body)
9 are “essential” needed in diet: (Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Threonine, Tryptophan, Valine)
Nonessential and Essential Amino Acids for Humans and the Albino Rat
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Cellular proteins can also be targeted for destruction
.•Used to degrade
-Misfolded proteins
-Foreign proteins
-Unwanted proteins
•Same end point as dietary proteins:
-Individual amino acids
Phenylketonuria (PKU)
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Phenylketonuria (PKU) description
.•Absence/deficiency of Phenylalanine hydroxylase (PAH) – classical PKU
•Autosomal recessive disorder
•Associated with increased phenylalanine (Phe) levels (toxic)
•Untreated individuals exhibit signs of impaired brain development
•Treatable condition – Reduced protein diet supplemented with tyrosine
•Incidence in UK – 1 in 10,000 live births
•Neonatal screening programme (carried out on day 5)
Phenylketonuria (PKU) - clinical features
.•Normal at birth with near normal blood Phelevels
•Phe levels rise rapidly once feeding is established
•Days 3-4 may present with irritability and feeding difficulties
•If untreated, delayed mental development and neurological features are evident by 6 months of age
•Musty odour
Phenylketonuria (PKU) Diagnosis - “Guthrie Card”
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Phenylketonuria (PKU), diagnosis
.•Positive screening test
•Quantitativeamino acid analysis
•Confirmation of increased blood Phe level
•Typically decreased blood Tyrosine (Tyr) level
•Presumptive diagnosis of PKU
•Dietary treatment started immediately
Phenylketonuria (PKU), Amino acid analysis
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Phenylketonuria (PKU) treatment
.•Low protein diet supplemented with “protein” substitute
•Maintain blood Phe levels between 120 – 360 umol/l
•Blood Tyr maintained at upper limit of reference range
•Monitor vitamin and trace element status
•Managed by multi-disciplinary team
- Dietitians
- Metabolic physicians
- Biochemists
- Genetic counselling
Phenylketonuria (PKU)- how it looks on people
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protein catabolism
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Removal of nitrogen from body
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THE UREA CYCLE
.•CYCLE IS SPLIT BETWEEN MITOCHONDRIAL MATRIX AND CYTOSOL
•5 ENZYMES CATALYSE THE CYCLE IN THE LIVER AND THEIR CONCENTRATIONS INCREASE OR DECREASE IN RESPONSE TO HIGH OR LOW PROTEIN DIETS.
•CPS1 IS THE REGULATORY ENZYME
•N-ACETYLGLUTAMATE IS ALLOSTERIC ACTIVATOR OF CPS1
Urea Cycle Defects
.•Rare group of inherited metabolic disorders
•6 inherited disorders of the urea cycle
•Most common is ornithine transcarbamoylase (OTC) deficiency
–Incidence of 1 in 40,000 births in UK
•OTC has X-linked inheritance, rest are autosomal recessive
•Characterised by hyperammonaemia (elevated blood ammonia level) – highly toxic