GB 11. Post-Absorption Processing of Proteins Flashcards
What are amino acids the building blocks of?
protein
What are amino acids the precursors of?
[1] haem
- glycine (succinyl CoA)
[2] nucleic acids
- purine + pyrimidines
- aspartate, glycine + glutamine
- aspartate + glutamine
[3] hormones
- e.g. thyroxine
[4] neurotransmitters
- e.g. dopamine, catecholamines
[5] biologically active peptides
- e.g. gonadotropins, PTH, insulin
Where are the 2 places that circulating amino acids come from?
[1] the diet
[2] protein turnover
What is the process of protein turnover?
- proteins are degraded into amino acids
- amino acids can be catabolized (can be used as a source of fuel for prolonged fasting and exercised)
- amino acids can also be used for de-novo synthesis to create proteins once again
What is the half lives of most proteins and the half lives for some enzymes?
[1] MOST PROTEINS
- half life of 2 to 3 days
- e.g. cytochromes
[2] SOME ENZYMES
- half life of around 30 minutes
- e.g. HMG-CoA Reductase
What are 2 factors that control protein degradation?
[1] N-Terminal Residue
- it determines the protein half-life
[2] “PEST” Amino Acid Sequences
- Pro (P), Glu (E), Ser (S), Thr (T)
- they are rapidly degraded
- degraded by lysosomal peptidases
Are amino acids stored?
No!
They are either:
[1] re-used in protein synthesis
[2] broken down
What are the 2 protein degradation systems?
[1] Ubiquitin - Proteasome System
- energy dependent
[2] Lysosomal Enzymes
- not energy dependent
There is a homeostasis and balance in maintaining circulating amino acids. This is dependent on….[2]
[1] utilisation of amino acids by tissues
[2] release of amino acids following protein degradation
What are the 2 principles organs involving in maintaining circulating amino-acid levels?
[1] Muscle
- generates more than 50% of circulating amino acids
[2] Liver
- gluconeogenesis
- urea cycle (utilisation and excretion of NH3)
Compare the amio acid transport in fasting states and a protein load state.
SLIDE 12
FASTING:
- all go towards liver (to create energy)
What is the Glucose/Alanine Cycle? (in other words, hepatic gluconeogenesis)
[1] in MUSCLE, ALANINE is created by the TRANSAMINATION of PYRUVATE
[2] Alanine sent from muscle to the liver
[3] Liver uses ALANINE to create GLUCOSE
[4] Glucose from the liver is sent to the muscle
What are glucogenic amino acids?
The breakdown of these amino acids yield TCA cycle intermediates which can be used to make glucose
What are Ketogenic amino acids?
The breakdown of these amino acids yields acetoacetate (Acetyl-CoA)
What are the 8 essential amino acids?
[1] Isoleucine (Ile) [2] Leucine (Leu) [3] Valine (Val) [4] Lysine (Lys) [5] Methionine (Met) [6] Phenyalanine (Phe) [7] Threonine (Thr) [8] Tryptophan (Try)
What are the 2 semi-essential amino acids? (the ones that are essential for children)?
[1] Arginine (Arg)
[2] Histidine (His)
What are the 3 non-essential amino acids that are formed from the essential amino acids?
[1] Cystine (Cys)
[2] Tyrosine (Tyr)
[3] Hydroxylysine (Hyl)
How many non-essential amino acids are formed from amphibolic (anabolic + catabolic) intermediates?
9
What are the 3 enzymes that play a central role in the synthesis of the non-essential amino acids that come from amphibolic intermediates?
[1] Transaminases*
[2] Glutamine Synthetase
[3] Glutamate Dehydrogenase
What are amphibolic intermediates?
created from both anabolic and catabolic intermediates
What is phenylketonuria? It is a deficiency of what enzyme?
Phenylketonuria - accumulation of phenylketones in the urine
- deficiency in the phenylalanine hydroxylase enzyme converting phenylalanine to tyrosine
Why is the synthesis of Glutamine (Gln) important?
in addition to creating glutamine, the reaction is useful for STORING FREE AMMONIA in a NON-TOXIC FORM
(NH3 becomes NH2 in the glutamine structure)
What are characteristics of the Transaminase (Aminotransferase) reaction?
- between amino acid and alpha-keto acid
What is the most abundant enzyme in human tissues?
transaminases
What is the most abundant enzyme in human tissues? What are they used for?
transaminases
- used in amino acid synthesis + degradation
In transaminases, which pair is the most widely used “donor-acceptor couple”?
Glutamate-alpha-Ketoglutarate
What are the 2 most important transaminase enzymes + reactions?
[1] Alanine Aminotransferase
[2] Aspartate Aminotransferase
How are amino acids degraded in transamination reactions?
through the removal of amino group:
- elimination from body in the form of urea (transamination + urea cycle)
When the amino groups are removed from amino acids, what must be done/taken into consideration?
NH3 is highly toxic
- the amino groups must be collected in a non-toxic form (primarily GLUTAMATE)
What reaction is glutamate dehydrogenase involved in?
- involved in reversible reaction
- involved in conversion between glutamate and alpha-ketoglutarate
What is oxidative deamination?
- part of the glutamate dehydrogenase reaction
- converting glutamate to alpha-ketoglutarate
- removal of NH3 in the process
What is reductive amination?
- part of the glutamate dehydrogenase reaction
- converting alpha-ketoglutarate to glutamate
- addition of NH3
What does the enzyme glutaminase do? Why is this reaction important?
- converts glutamine to glutamate
- important because NH3 is released from the glutamine
What happens to the carbon skeletons of most amino acids (other than some exceptions)?
- they become intermediates of the TCA cycle
- used in gluconeogenesis
What happens to the carbon skeletons of most amino acids (other than some exceptions)?
- they are degraded to intermediates of the TCA cycle
- used in gluconeogenesis
What happens to the carbon skeletons of these amino acids: tryptophan phenylalanine tyrosine isoleuce
- both glucogenic and ketogenic
- they can undergo gluconeogenesis or ketogenesis
What happens to the carbon skeletons of these amino acids:
leucine
lysine
- they are ketogenic
- they are degraded to Acetyl-CoA
- used in ketogenesis
Where does the urea cycle take place in?
in the liver
For the urea cycle to take place in the liver, what must be transported there first?
amino nitrogen
What are the 2 ways that amino nitrogen is transported in the circulation?
[1] Alanine
- made from the pyruvate in the muscle
[2] Glutamine
- made from glutamate in most tissues
Free ammonia (NH3) is produced in the body in small quantities by…[4]
[1] breakdown of purines + pyrimidines
[2] breakdown of amines (dietary) + monoamines
[3] breakdown of glutamine
[4] bacterial digestion of urea in the gut
Where is urea synthesized? How is urea excreted from the body?
- urea is synthesized in the liver
- it is water soluble and can be transported in the vascular circulation
- it is excreted by the kidneys
In renal failure, what may appear in regards to urea?
- blood urea increases [uraemia]
- the kidneys do not excrete as much urea as they are supposed to
What is the chemical structure of urea? In the biosynthesis of urea, what is required?
it contains 2 amino groups
- one comes from carbamoyl phosphate (synthesized from glutamate)
- the other comes from the amino acid Aspartate
- 3 ATP molecules are required per urea molecule produced!
Normally, what are the levels of free ammonia in the blood serum?
5 to 50 umol/L
What happens if ammonia levels exceed the capacity of the urea cycle?
levels can rise over 1000 umol/L
- leads to hyperammonaemia
What are the 2 causes of hyperammonaemia?
[1] Acquired Hyperammonaemia
- e.g. liver disease/failure
[2] Hereditary Hyperammonaemia
- e.g. an inherited urea cycle defect
What are the effects of Hyperammonaemia?
- CNS toxicity
- tremors, slurred speech, vomiting, cerebral oedema
- coma, death…
What is the most common urea cycle disorder in humans?
- OTC deficiency
- Ornithine Transcarbamylase is the final enzyme in the proximal portion of the urea cycle - responsible for converting carbamoyl phosphate and ornithine into citrulline
- X linked disorder (approx. 20% of female carriers of the OTC gene are symptomatic)
- lack of the OTC enzyme results in excessive accumulation of nitrogen, in the form of ammonia (hyperammonemia) in the blood
- excess ammonia, which is a neurotoxin, travels to the CNS through the blood (resulting in symtpoms and physical findings associated with OTC deficiency)
- symptoms include: vomiting, refusal to eat, progressive lethargy, coma
- severity and age of onset of OTC deficiency vary
What are the symptoms of OTC Deficiency?
- vomiting
- refusal to eat
- progressive lethargy
- coma
