S1 L2 - Protein and amino acid metabolism Flashcards
Major nitrogen containing products
- *Creatinine:**
- What is this
- How is it produced?
- What is it proprotional too?
- What is it another indicator of?
Major Nitrogen containing compounds:
• Amino acids
• Proteins
• Purines + Pyrimidines (DNA / RNA)
Smaller amounts of others –
e.g. • Porphyrins (haem)
• Creatine phosphate
• Neurotransmitters (e.g. dopamine)
• Some hormones (e.g. adrenaline)
Creatinine:
- What is this
Breakdown product of creatine & creatine phosphate in muscle
- How is it produced?
Usually produced at constant rate depending on muscle mass (unless muscle is wasting) • Filtered via kidneys into urine
- What is it proprotional too?
Creatinine urine excretion over 24h proportional to muscle mass
• Provides estimate of muscle mass
- What is it another indicator of?
Also commonly used as indicator of renal function (raised level on damage to nephrons)
- *Nitrogen balance**
- 3 ‘types’ of ‘balance’
- Diagram to show this
N equilibrium:
Intake = output. No change in total body protein. Normal state in adult.
Positive N balance:
Intake > output. Increase in total body protein. Normal state in growth & pregnancy or in adult recovering from malnutrition
Negative N balance:
Intake < output. Net loss of body protein. Never normal. Causes include trauma, infection, or malnutrition.
- *Protein turnover**
- Flow diagram to show this
Glucogenic and ketogenic amino acid examples
- Flow diagram to show this
Glucogenic and ketogenic amino acid examples:
Glucogenic - Alanine
Ketogenic - Lysine
Both - Tryptophan
(picture attached)
- *Mobilisation of protein reserves**
- hormones
- Cushing’s Syndrome, why is there striae?
9 Essential amino acids
What are conditionally essential amino acids? Explain and name them
What is high and low quality protein?
- *Mobilisation of protein reserves**
- hormones (pic)
9 Essential aa:
- *I**soleucine
- *L**ysine
- *T**rytophan
- *H**istidine
- *L**eucine
- *M**ethionine
- *P**henylalanine
- *T**hreonine
- *V**aline
What are conditionally essential amino acids?
Arginine, cysteine, tyrosine
Children and pregnant women = high rate of protein synthesis
What is high and low quality protein?
Protein of animal origin considered “High quality” (Contain all essential amino acids)
• Proteins of plant origin generally considered “lower quality” since most are deficient in one or more essential amino acids.
• Therefore essential that vegetarian diet obtains protein from a wide variety of plant sources
- *Amino acid synthesis:**
- where can aa be synthesised from?
- What is tyrosine, cysteine, histidine, arginine needed for?
- Where can aa be synthesised from?
In addition to dietary intake, body can synthesise some amino acids it requires (the non-essential amino acids). Carbon atoms for non-essential amino acid synthesis come from:
• Intermediates of glycolysis (C3)
• Pentose phosphate pathway (C4 & C5)
• Krebs cycle (C4 & C5)
- What is tyrosine, cysteine, histidine, arginine needed for?
Tyrosine - Thryoid hormone
Cysteine - Glutathione
Histidine - Histamine
Arginine - NO synthesis
Removal of nitrogen from amino acids
Removal of amino group is essential to allow carbon skeleton of amino acids to be utilised in oxidative metabolism
• Once removed nitrogen can be incorporated into other compounds or excreted from body as urea
• Two main pathways facilitate removal of nitrogen from amino acids:
- Transamination
- Deamination
- *Transmination**
- What is this?
- The major equation
- The 2 enzymes involved - what they convert…
- *Key aminotransferase enzymes:**
- Names of 2 enzymes involved
- What these enzymes can signify
- Conditions where these enzymes are raised
Transamination - transferring amin group with a keta acid, creating a different aa and keto acid
Amino acid 1 + Keto acid 2 Amino acid 2 + Keto acid 1
Glutamate and aspartate amino acids can readily feed into the urea cycle - they can feed in much better than other amino acids. Therefore, they aid the removal of nitrogen from aa.
Pic attached:
- 2 enzymes involved
- What these enzymes can signify
- Conditions where these enzymes are raised
- *Deamination**
- What is this?
- Where does it occur?
- Describe the characteristics of ammonia
Deamination
- What is this?
Liberates amino group as free ammonia
- Where does it occur?
Liver and kidney
- Describe the characteristics of ammonia
Ammonia is very toxic and must be removed. Ultimately converted to urea or excreted directly in urine
- *Urea**
- Urea - characteristics
- Urea cycle (Few key parts of the cycle)
- Urea cycle: Enzymes, where does it occur, how the enzymes increase in rate…
Urea - Characteristics:
• High nitrogen content
• Non-toxic
• Extremely water soluble
• Chemically inert in humans (bacteria can break it down to release NH3)
• Most urea is excreted in urine via the kidneys
• Also performs useful osmotic role in kidney tubules
Urea - Urea cycle:
pic
Urea cycle:
- Enzymes: involves 5 enzymes
- Where does it occur: Liver
- How the enzymes increase in rate:
• Amount of urea cycle enzymes normally related to need to dispose of ammonia • High protein diet induces enzyme levels • Low protein diet or starvation represses levels • Cycle is inducible but not regulated
- *Problems with urea cycle:**
- Refeeding syndrome
- *Defects in the urea cycle:
- **genetics
- leads to…
Refeeding syndrome:
• Can occur when nutritional support given to severely malnourished patients
• Ammonia toxicity significant factor (urea cycle down regulated)
• Re-feed @ 5 to 10 kcal/kg/day. Raise gradually to full needs within a week
Risk factors: BMI <16, Unintentional weight loss>15% in 3-6 months, 10 days or more with little or no nutritional intake
Defects in the urea cycle:
• Autosomal recessive genetic disorders caused by deficiency of one of enzymes in the urea cycle
• Mutations cause a partial loss of enzyme function
• Leads to: – hyperammonaemia – accumulation/excretion of urea cycle intermediates
- *Defects in the Urea cycle:
- ** Clinical picture (NH3 toxicity), severity depends on…
- *-** When do the urea cycle disorders show?
- Mangement
- Symptoms
Biochemical Basis of Ammonia Toxicity
Defects in the Urea cycle:
- Clinical picture (NH3 toxicity), severity depends on…
Severity depends on: • nature of defect • amount of protein eaten
- When do the urea cycle disorders show?
• Severe urea cycle disorders show symptoms within 1 day after birth. If untreated, child will die. • Mild urea cycle enzyme deficiencies may not show symptoms until early childhood
- Mangement:
• Low protein diet • Replace amino acids in diet with keto acids
- Symptoms:
• Vomitting • Lethargy • Irritability • Mental retardation • Seizures • Coma
Biochemical Basis of Ammonia Toxicity:
Readily diffusible and extremely toxic to the brain, blood levels need to be kept low.
Several potential toxic effects:
• Interference with amino acid transport and protein synthesis
• Disruption of cerebral blood flow
• pH effects (alkaline)
• Interference with metabolism of excitatory amino acid neurotransmitters (e.g. glutamate and aspartate)
• Alteration of the blood–brain barrier
• Interference with TCA cycle (reacts with α-ketoglutarate to form glutamate)
- *Transport of amino acid nitrogen from peripheral tissues**
- including in the blood
- *Clinical problems of amino acid metabolism**
- What is the most common problem of these diseases affecting aa metabolism?
- How are the commonly tested?
- Give some examples of non amino acid metabolism conditions tested for?
- Give some examples of inborn errors of metabolism
- *Transport of amino acid nitrogen from peripheral tissues:**
- including in the blood
Clinical problems of amino acid metabolism:
- What is the most common problem of these diseases affecting aa metabolism?
Affects enzymes
- How are these commonly tested?
Heel prick test
- Give some examples of non amino acid metabolism conditions tested for?
Sickle cell anaemia, Cystic fibrosis, Congenital hypothyrodism
- Give some examples of inborn errors of metabolism
Phenylketouria (PKU), Homocystinuria
- *Phenylketonuria (PKU)
- **Equations to show this
- Issue with which enzyme?
- What product is then lacking? (think about pathway)
- What is the role of this product?
- What build up causes the issue?
- Genetic issue?
- Symptoms
- What is a niche sign of this condition?
- Treatment
Phenylketonuria (PKU):
- Equations to show this:
pic below
- Issue with which enzyme?
Phenylalanine hydroxylase
- What product is then lacking? (think about pathway)
Tyrosine
- What is the role of this product?
includes - Adrenaline, Noradrenaline, Dopamine, Thyroid hormone
- What build up causes the issue?
Phenylalanine
- Genetic issue:
Autosomal recessive
- Symptoms:
Microcephaly, seizures, coma, severe intellectual disability, developmental delay, hypopigmentation
- What is a niche sign of this condition?
Urine smells musty (because of the ketones in it - phenylketone)
- Treatment:
Strictly controlled low phenylalanine diet enriched with tyrosine, avoid artifical sweetners (contains phenylalanine), avoid high protein foods like milk, egg, meat
Phenyalanine - Effect on brain development?
- Phenylalanine is a large neutral amino acid (LNAA)
- Competes for transport across the blood brain barrier via Large Neutral Amino Acid Transporter (LNAAT)
- Excess phenylalanine can saturate this transporter
- Levels of other LNAA in the brain decreased
- Protein/neurotransmitter synthesis inhibited
- Brain development affected
- Causes mental retardation
- *Homocystinuria**
- Pathway
- Defect in which enzyme
- Type of genetic issue
- Symptoms
- Treatment
- Pathway
pic attached
- Defect in which enzyme
Cystathionine-beta-synthase
- Type of genetic issue
autosomal recessive mutation
- Symptoms
Affects connective tissue, muscles, CNS, CVS
- Treatment
Low-methionine diet; avoid milk, meat, fish, cheese, eggs; cysteine, vitamin B6, B12, folate supplement
