Protein & Amino Acid Metabolism Flashcards
How is Creatinine formed?
- Breakdown product of CREATINE and CREATINE PHOSPHATE in muscle
- Produced at a constant rate depending on muscle mass (unless muscle is wasting)
Explain how creatinine is used as a clinical marker
- Provides an estimate of muscle mass (creatinine measured over 24hrs in urine -> proportional to muscle mass)
- Used as an indicator of renal function as it provides an estimate for glomerular filtrate rate (raised levels indicate damage to nephrons)
Define protein turnover
Balance between protein synthesis and protein degradation (proteolysis)
List 5 Nitrogen containing compounds found in the body
- Amino acids
- Proteins
- Purines and pyrimidines (DNA/RNA)
- Neurotransmitters e.g. Dopamine
- Some hormones e.g. Adrenaline
Define nitrogen balance
The balance between the nitrogen taken into our bodies through diet and the nitrogen lost or excreted from body
Explain the importance of nitrogen balance in the body
- Positive N balance: INTAKE > OUTPUT so there is an increase in total body protein
- Negative N balance: INTAKE
What is the difference between GLUCOGENIC and KETOGENIC amino acids?
- GLUCOGENIC amino acids can be converted into glucose via gluconeogenesis
- KETOGENIC amino acids can be degraded into Acetyl CoA, which is the precursor of ketone bodies
List the amino acids which are GLUCOGENIC
- Alanine
- Cysteine
- Aspartic acid
- Asparagine
- Arginine
- Histidine
- Proline
- Glutamine
- Methionine
- Valine
- Glycine
- Serine
List the amino acids which are KETOGENIC
- Lysine
- Leucine
List the amino acids which can be either GLUCOGENIC or KETOGENIC
- Tryptophan
- Threonine
- Tyrosine
- Phenylalanine
- Isoleucine
What are the 9 essential amino acids that cannot be synthesised by the body?
- Isoleucine
- Lysine
- Threonine
- Histidine
- Leucine
- Methionine
- Phenylalanine
- Tryptophan
- Valine
What is the name of the process by which amino acids can be converted to glucose?
GLUCONEOGENESIS
What is the effect of insulin on protein turnover?
- INCREASES protein synthesis
- DECREASES protein degradation
Explain the role of TYROSINE in the synthesis of important N-containing compounds
- Production of thyroid hormones (T3 and T4 synthesised from Tyrosine residues)
- Production of menalin (skin)
- Production of NEUROTRANSMITTERS e.g. noradrenaline
- Absence of Tyrosine can lead to mental retardation
State the use of nitric oxide in the body and the amino acid derivative
- Derived from ARGININE
- Role in vasodilation
- Gaseous signalling molecule
What is HISTAMINE?
- Nitrogenous compound produced from HISTIDINE
- Secreted by mast cells/basophils during immune/hypersensitivity response
What is TRANSAMINATION?
The transfer of an amino group from one amino acid to a keto acid, forming an amino acid which can enter the urea cycle and undergo DEAMINATION
What is DEAMINATION?
The removal of an amino group from an amino acid, producing AMMONIA and a keto acid
Where does DEAMINATION occur?
LIVER and KIDNEY
How can the body synthesise amino acids?
Use of carbon atoms from:
- Intermediates of glycolysis (C3)
- Pentose phosphate pathway (C4, C5)
- Krebs cycle (C4, C5)
Amine group provided through TRANSAMINATION or from ammonia
Why is the removal of nitrogen from amino acids essential?
- Carbon skeleton can be utilised in oxidative metabolism
- Once removed N can be incorporated into other compounds or excreted as UREA
Describe the formation of GLUTAMATE through transamination of ALANINE
- Alanine + a-ketoglutarate —-> Glutamate + pyruvate
- Catalysed by the enzyme ALANINE AMINOTRANSFERASE (ALT)
Explain the role of ASPARTATE AMINOTRANSFERASE (AST) in transamination
- Conversion of Glutamate to Aspartate
- Glutamate + α-ketoglutarate —-> Aspartate + oxaloacetate
- Aspartate can undergo DEAMINATION and enter Urea Cycle
Why must ammonia be converted to urea?
- Ammonia is highly toxic
- Urea is non-toxic and chemically inert and can be excreted from body in the urine
Describe the potential toxic effects of ammonia
- Increase in blood pH (alkaline)
- Interference with amino acid transport and protein synthesis
- Alteration of blood-brain barrier
- Interference with Krebs cycle (reacts with a-ketoglutarate to form Glu)
How is ammonia transported in the blood?
- Combines with Glutamate to form GLUTAMINE, which is transported in blood to the liver where it is converted back to Glu and NH3
- Combines with pyruvate to form Alanine which is transported to liver and used to synthesise Glutamate through transamination
State the significance of the heel prick test in newborns
- Systematically screen for inborn errors in amino acid metabolism
- Diseases can be identified early so treatment methods can be put in place to avoid permanent damage
- These may include modifications to the diet
Explain how Phenylketonuria (PKU) can lead to the presence of phenylketones in the urine
- Deficiency in PHENYLALANINE HYDROXYLASE
- Accumulation of Phenylalanine which undergoes transamination to form PHENYLPYRUVATE
- Phenylpyruvate can form phenylketones such as phenyllactate and phenylacetate which are present in the urine
Why might PKU lead to mental retardation?
- Deficiency in Phenylalanine Hydroxylase enzyme means that phenylalanine cannot be converted to TYROSINE
- Tyrosine is important in the the production of various neurotransmitters - other pathways affected
What are the treatment methods for PKU?
- Low Phenylalanine in diet
- Avoid high protein foods e.g. meat, fish, eggs
- Avoid artificial sweeteners (may contain Phe)
What causes Homocystinuria?
- AUTOSOMAL RECESSIVE DISORDER
- Deficiency of CYSTATHIONINE B-SYNTHASE enzyme means that Methionine cannot be broken down
- Accumulation of HOMOCYSTEINE and methionine - HOMOCYSTINE present in urine
- High levels of homocysteine and methionine are associated with CVD
What are the treatment methods for Homocystinuria?
- Low methionine diet
- Avoid meat, fish, eggs, nuts and nut butters
- Supplement diet with Cysteine, Vitamins B12 and B6, Betaine and Folate
How could you clinically test for high levels of ALT and AST and what could this indicate?
- Plasma levels of ALT and AST are measured routinely as part of a liver function test (blood test)
- High levels indicate extensive cellular necrosis (conditions such as viral hepatitis, autoimmune liver disease and toxic injury)
Which 2 amino acids can undergo deamination?
- GLUTAMATE
- ASPARTATE
What causes Phenylketonuria (PKU)?
- Autosomal recessive disorder due to mutation of gene coding for PHENYLALANINE HYDROXYLASE
- Gene located on chromosome 12
What diseases can occur due to lack of protein in diet?
- Kwashiorkor (protein deficient)
- Marasmus (energy deficient)
Explain how lack of protein can cause oedema
- Decrease in oncotic pressure due to lack of protein in blood
- Hydrostatic pressure > oncotic pressure which leads to net flow of fluid out of capillaries and into tissues
- This can cause swelling of tissues (oedema)
Give 3 examples of high N-containing compounds in the body
- Proteins
- DNA
- RNA
Give 3 examples of low N-containing compounds in the body
- Amino acids
- Purines/pyrimidines
- Neurotransmitters
How does Nitrogen enter and leave the body?
- Most N enters as proteins
- Most N leaves body through excretion of urine (urea, creatinine, ammonia and uric acid)
- Some N lost directly (skin, hair nails etc.)
When might the body show a positive N balance?
During:
- Growth
- Pregnancy
- Convalescence
- Tissue repair
Explain why tyrosine, cysteine and arginine are not classed as ‘essential amino acids’
- Can be synthesised by the body
- Tyrosine can be synthesised from Phenylalanine
- Cysteine can be synthesised from Methionine
- Arginine can be synthesised from Citrulline
How can cells attempt to reduce the toxicity of ammonia?
- Synthesis of GLUTAMINE from NH3 and glutamate using GLUTAMINE SYNTHETASE
- Glutamine is transported to liver and kidney where it is converted back to glutamate and NH3 using GLUTAMINASE
- NH3 can be converted to urea in liver or directly excreted in urine in kidneys
