Session 1- protein and aa metabolism Flashcards
What effect do these hormones have on protein synthesis?
- Insulin
- Growth hormone
- Cortisol
How does cortisol exert its effect?
Insulin and growth hormone promote uptake of amino acids and protein synthesis
Cortisol promotes proteolysis in muscle by activating aminotransferases in the liver
Is excess protein stored?
No, the amino acids are converted to metabolites or excreted
What is the first step in amino acid breakdown?
Removal of the amino group by transamination/ deamination
Amino acid catabolism; What happens to the amino group?
What is the remaining structure called?
If not transferred to another aa, it is converted to urea and excreted via the urine
Urea; (CO(NH2)2)
C-skeleton of the amino acid
What are ketogenic and glucogenic amino acids?
The C-skeletons of ketogenic amino acids produce acetyl CoA which can make ketone bodies
C-skeletons of glucogenic amino acids produce intermediates in gluconeogenesis. E.g. pyruvate
Name two ketogenic amino acids
Name amino acids which are both ketogenic and glucogenic
Lysine & leucine
Tryptophan Tyrosine Isoleucine Phenylalanine Threonine
Metabolism of glucose, fatty acids, amino acids and ketone bodies all produce which molecule?
Acetyl CoA
enters the TCA cycle
How many kg of nitrogen is there in the body?
Most of the nitrogen in the body is found where?
Approx. 2kg
Mostly proteins (90%) then DNA & RNA
Average half life of a protein?
Total protein turnover per day in an adult?
80 days
300-400 g per day
What is a positive nitrogen balance?
When does it occur?
Taking in more protein than you excrete
Periods of active growth, pregnancy and tissue repair
What is a negative nitrogen balance?
When does it occur?
Taking in less nitrogen than you excrete
Starvation, malnutrition, trauma
How does nitrogen enter and leave the body?
Enters mostly in protein
Leaves via - urea (85%) - creatinine - ammonia - uric acid some direct loss of protein via hair, skin, nails
How to remember the 10 essential amino acids?
PVT TIM HALL
Phenylalanine valine threonine tryptophan isoleucine methionine histidine arginine (conditional) leucine lysine
Name three amino acids which are conditionally essential
Explain when they become essential
Tyrosine - only if phenylalanine is low (its precursor)
Arginine - only during periods of active growth bc the body can produce small amounts
Cysteine - only if methionine (its precursor) is low
Which amino acid is the precursor for Tyrosine?
Phenylalanine
Which amino acid is the precursor for Cysteine?
Methionine
Normal fasting concentration of amino acids in the blood?
3mmol/L
Which 4 non-essential amino acids make up 50% of the free pool?
glutatmine, alanine, proline, glycine
Why do you need to keep taking in amino acids if most are recycled?
To replace those which are lost
Where do the carbon and nitrogen atoms come from to make new amino acids?
- carbon from intermediates of glycolysis, the pentose phosphate pathway and the Krebs Cycle
- amino group from transamination or ammonia
What happens to excess amino acids?
Converted to intermediates of carbohydrate and lipid metabolism OR
oxidised for energy
Which two signalling molecules are made from amino acids?
nitric oxide (from L-arginine)
Hydrogen sulphide (from L-cysteine)
These amino acids are used to make what nitrogenous compounds?
- Trytophan
- Histidine
- Tyrosine
- Glycine
- seratonin, 5-HT
- histamine
- thyroid hormones, melanin, catecholamines
- purines, porphyrins, creatine, glutathione
Where does most amino acid catabolism occur?
How does use of acetyl CoA change in starvation?
liver
Usually oxidised to CO2 and water but in starvation/ diabetes, it’s converted to ketone bodies and glucose
Which 2 aminotransferases do we test for liver function?
What does the amino acid react with?
What is it converted to?
Alanine aminotransferase
Aspartate aminotransferase?
(keto acid)
alpha ketoglutarate
> glutamate
aminotransferases convert these amino acids to what?
- Alanine
- Aspartate
Aspartate is an important intermediate in synthesis of ____ .
- Alanine becomes Pyruvate
- Aspartate becomes Oxaloacetate
- Urea
Where do D amino acids come from and how do we use them?
They come from plants and bacteria so enter the body through the diet
We do NOT use them in protein synthesis, instead they are converted to keto acids and NH3, ammonia
Why do we convert D-amino acids to keto acids?
Keto acids are not optically active
What does glutaminase do?
Glutamine to glutamate + ammonia (NH3)
What does glutamaTe dehydrogenase do?
Glutamate to alpha ketoglutarate
+ NH4+ and NADH
When can amino acids be toxic?
What can this cause?
If they’re not broken down correctly;
Accumulate/ toxic byproducts of improper breakdown
Mental retardation and developmental abnormalities
What does PKU stand for?
What process is defective in PKU?
Phenylketonuria (PKU)
Conversion of phenylalanine to tyrosine
Which enzyme is usually defective in phenylketonuria?
Normal range of phenylalanine in the blood?
Conc. in PKU?
phenylalanine hydroxylase
Usually lower than 0.1, can rise to 1mmol/ L in PKU
If undiagnosed what are the consequences of PKU and why?
What precaution does the UK take to diagnose early?
- inhibition of brain development
phenylpyruvate (metabolite of secondary pathways) - inhibits pyruvate uptake into mitochondria
- interferes with energy metabolism in the brain
Screened for in the heel prick test performed on new born babies
In homocystinuria, which amino acid can’t be broken down?
What is the deficient enzyme?
Methionine
(Cysteine is formed from methionine)
CBS enzyme
(Cystathionine beta synthase)
How is homocystinuria inherited?
Why is the concentration of plasma methionine high?
What is present in the urine?
autosomal recessive
- Homocysteine can’t be converted to cysteine
- It accumulates and some is converted to methionine
- homocystINE (oxidised homocysteine)
How does untreated homocystinuria present?
Which other condition can it be mistaken for in children?
disorders of connective tissue, muscle, CNS and the cardiovascular system
Marfan’s Syndrome
Which protein is not expressed in Marfan’s Syndrome?
What happens to this protein in homocystinuria?
Fibrillin 1
the structure is disrupted
Where does ammonia in the body come from?
How does it mostly exist in the body?
produced by tissues and absorbed from gut
As the ammonium ion, NH4+
Why are levels of plasma ammonia very low?
Symptoms of high ammonia?
- Toxic to cells
- CNS is extremely sensitive to ammonia
slurred speech, blurred vision, tremors, coma, death
How does hyperammonia cause its neurological symptoms?
Two theories
- Reacts with alpha ketoglutatrate;
- removing it from the TCA cycle (slows)
- disrupts energy supply to brain
Change intracellular pH thus affecting NT release
Why is hyperammonia seen in liver disease?
Liver is site of NH3 detoxification
Two ways ammonia is detoxified in the liver?
- Converted to urea
- used in synthesis of nitrogenous compounds
Which amino acid is highest in the blood?
When do its levels rise further?
Glutamine
After a protein rich meal
Where does aspartate come from?
Transamination of oxaloacetate
The nitrogen atoms in Urea come from ___ &____?
Aspartate and ammonium, NH4+
Why does re-feeding syndrome occur?
Enzymes of the urea cycle are induced to work; if the diet is low in protein, the enzymes deregulate
When given a high protein meal, the body cannot detoxify the ammonia (by conversion to urea) and the patient suffers hyperammonaemia
What underlying condition creates the neurological symptoms of refeeding syndrome?
Which enzymes are not functioning?
Hyperammonaemia
(bc they can’t detoxify the ammonia from protein metabolsim)
Inducible enzymes of the urea cycle
Where in the body does bacteria break urea into ammonia which is absorbed?
The small intestine (urea can diffuse in)
The C skeletons of Ketogenic amino acids produce _____.
What do glucogenic C skeletons produce?
What are the glucogenic products used in?
Acetyl CoA
glutamic acid
aspartic acid
serine
- gluconeogenesis
What size are amino acids which are both ketogenic and glucogenic?
Large amino acids; phenylalanine tyrosine tryptophan isoleucine threonine
Which reaction does all these enzymes perform?
- D amino acid oxidase
- Glutaminase
- Glutamate dehydrogenase
Which toxic by-product do they produce?
Deamination (removal of amino group)
Ammonia, NH3
Why is glutamate dehydrogenase enzyme in aa metabolism?
Where is the enzyme?
Reversible reaction; catalyses amino acid synthesis and breakdown
glutamate <> alpha- ketoglutarate
Which processes produce Ammonia?
Deamination by
- glutaminase and
- glutamate dehydrogenase
- D amino acid oxidase
- Produced by bacteria in the gut from urea
Glutaminase reaction
Deamination
- glutamine to glutamate (acid) and NH3
Glutamate dehydrogenase
Deamination
- glutamate to alpha- ketoglutarate
Glutamate, NAD+ and water»_space;
a- Ketoglutarate, NH4+, NADH and H+
How does ammonium become ammonia?
NH4+ and OH-
>
NH3 + H2O
