Protein And Amino Acids Flashcards
Nitrogen balance
N is 16% of proteins - western diet ~ 100g per day
N equilibrium - intake = output - normal state in adults Positive N balance - intake > output - normal state in growth and pregnancy or in an adult recovering from malnutrition Negative N balance - intake
Protein turnover
Free amino acids are used to produce energy in times of stress e.g. malnutrition
Glucogenic amino acids
Alanine
Glycine
Histidine
Ketogenic amino acids
Lysine
Leucine
Glucogenic and ketogenic amino acids
Tryptophan
Phenylalanine
Tyrosine
Mobilisation of protein reserves
- occurs during extreme stress - starvation
- under hormonal control
Protein synthesis - inhibited by glucocorticoids e.g. Cortisol
- activated by insulin and growth hormone
Protein degradation - inhibited by insulin and growth hormone
- activated by glucocorticoids e.g. Cortisol
Excessive protein breakdown can occur in Cushing’s syndrome (excess cortisol) weaken skin leading to purple striae formation
Amino acid structure
H. H. OH |. |. | N---C----C=O |. |. H. R
20 different types
Joined by peptide bonds
Creatinine
a useful clinical marker
- breakdown product of creatine & creatine phosphate in muscle
- usually produced at a constant ratio and amount in urine is proportional to muscle mass over 24 hours (unless there is muscle wasting)
- men 14-26 mg/kg, women 11-20 mg/kg
- filtered via kidneys into urine - provides an estimate of muscle mass
- used as an indicator of renal function (raised levels - damage to nephrons)
Essential amino acids
If - Isoleucine Learned - Lysine This - Threonine Huge - Histidine List - Leucine May - Methionine Prove - Phenylalanine Truly - Tryptophan Valuable - Valine
Amino acid synthesis
C atoms come from - intermediates of glycolysis (C3) - pentose phosphate pathway (C4&C5) - kreb's cycle (C4&C5) The amino group is provided by the other amino acids by the process of transamination or from ammonia
Synthesis of important N containing compounds
Tyrosine
- thyroid hormones - adrenaline and dopamine
Histidine
- histamine
Arginine
- nitric oxide - signalling molecule for vascular dilation
Cysteine
- hydrogen sulphide - signalling molecule
- glutathione
Transamination
Most aminotransferase enzymes use alpha-ketoglutarate to funnel the amino acid groups to glutamate
Exception is Aspartate aminotransferase which uses oxaloacetate to funnel amino acid group to Aspartate
- all require coenzyme pyridoxal phosphate which is a derivative of vitamin B6
Amino transferase removes amino group from one amino acid and adds them to a keto acid - glutamate/Aspartate (which can be dealt with in terms of the amino group)
Aminotransferase enzymes of clinical importance
Alanine aminotransferase (ALT)
- converts alanine to glutamate
Aspartate aminotransferase (AST)
- converts glutamate to Aspartate
Plasma levels of ALT and AST are measured routinely as part of the liver function test
High levels that cause extensive cellular necrosis
- viral hepatitis
- autoimmune liver diseases
- toxic injury
- death cap mushrooms that cause acute liver failure
Deamination
- liberates the amino group as free ammonia Occurs mainly in the liver and kidney - keto acids can be utilised for energy - ammonia (toxic) is converted to urea or excreted directly in the liver Enzymes - amino acid oxidises - glutaminase - glutamate dehydrogenase
Urea
- high nitrogen content
- non-toxic
- extremely water soluble
- inherit in humans
- excreted in urine via the kidneys
- useful osmotic role in kidney tubules
Urea cycle
Occurs in liver and involves 5 enzymes
- amount of urea cycle enzymes is related to need to dispose ammonia (can be downgraded in starvation - leads to refeeding syndrome - refeed @ 5-10kcal/kg/day)
- cycle is inducible but not regulated
Defects in urea cycle
- autosomal recessive genetic disorders (caused by deficiency of one of enzymes in the urea cycle
~ 1 in 30,000 live births
Mutations cause partial loss of enzyme function - complete loss is incompatible with life
Leads to - - hyperammonaemia
- accumulation/excretion of urea cycle intermediates
Severity depends on nature of defect and amount of protein eaten - severe show symptoms within a day of birth
- mild show symptoms in early childhood
LOW PROTEIN DIET, REPLACE AMINO ACIDS WITH KETO ACIDS
Ammonia Toxicity
- readily diffusible
- blood levels low (25-40umol/L)
potential side effects - interference with aa transport and protein synthesis
- disruption of cerebral blood flow
- pH affects (alkaline)
- interference with TCA cycle (reacts with alpha-ketogluterate to form glutamate)
- interference with the metabolism of excitatory amino acid neurotransmitters (glutamate and Aspartate)
Transport of ammonia
Glutamine
Ammonia + glutamate = glutamine
- transported to liver or kidney in blood - cleaved by glutaminase to reform glutamate and ammonia
- in liver ammonia is fed into the urea cycle
- in kidney ammonia is excreted directly as urine
Transport of ammonia
alanine cycle
Alanine is formed by transamination of pyruvate in the peripheral tissues
- transported to the liver by the blood where it is converted back to pyruvate by transamination
- amino group is fed via glutamate into the urea cycle
- pyruvate is used to synthesis glucose which can be fed back to the tissues
Heel prick test
- every child is screened systematically at birth for a variety of inborn problems of metabolism
- dietary modification can manage disease whereas untreated it could lead to mental retardation
Phenylketonuria (PKU)
Most common (~1 in 15,000 births)
- deficiency in phenylalanine hydroxylase
- autosomal recessive gene on chromosome 12
- accumulation of phenylalanine in tissue, plasma and urine
- phenylketones in urine
- musty smell
TREATMENTS
- strictly control phenylalanie in diet (avoid artificial sweetener, avoid high protein foods - meat, milk and eggs)
Not producing enough tyrosine which needed for noradrenaline and adrenaline, dopamine, melanin, thyroid hormones and protein synthesis
SYMPTOMS
- severe intellectual ability and developmental delay
- microcephaly (small head)
- seizures
- hypopigmentation
Homocystinurias
Problem breaking down methionine
- excess homocystine (oxidation of homocysteine) is excreted in urine
- autosomal recessive ~ 1 in 344,000
- defect in cystathionine beta-synthase most common
- affects connective tissue, muscles, CNS, CVS
TREATMENT
- low-methionine diet (acid milk, meat, fish, eggs, nuts and peanut butter)
- cysteine, vitamin b6, beating, b12 and folate suppliment
(Accumulation if methionine is less severed than accumulation of homocysteine so supplements are given to promote the conversion of homocysteine to methionine)
