Synthesis of AA and their derivatives Flashcards
Where can all AA be derived from?
from intermediates of metabolic pathways
Which organisms can synthesize all AA?
Bacteria and plants
Mammals synthesize _ AA from __ v Source of
Mammals synthesize 10 AA from intermediates of metabolic pathway
What are the sources of amino groups in synthesis of AA?
Glutamate and Glutamine
How many essential AA are there
9
Name essential AA and a mnemonic to memorize them
Veterinarian Prescribed High Lipid Meal To Increase Triglyceride Levels
Valine Phenylalanine Histidine Lysine Methionine Tryptophan Isoleucine Threonine Leucine
What are non-standard AA?
These AA are not used in protein synthesis
E.g. GABA, Homocystein
What is the 21st AA
Selenocysteine
- New AA that was discovered. Used in protein coding. It is synthesized on tRNA
Coded by UGA in context dependent manner
E.g. Glutathione Peroxidase is a protein that contains selenocysteine - this enzyme alleviates oxidative stress
How can AA be grouped?
AA can be categorized depending on the intermediate used to build the AA aka precursors
Name and describe the groups of AA + primary AA of each
Group 1: alpha-ketoglutarate (which comes from TCA)- glutamate
Group 2: 3-phosphoglycerate which is part of glycolysis.- Serine
Group 3: oxaloacetate is the precursor-> Aspartate
Group 4: Pyruvate. - Alanine
Group 5- phosphoenolpyruvate- tyrosine
What is special about tyrosine?
It is neither be essential nor non-essential Tyrosine can be made from phenylalanine. Mammals have an enzymatic system to make tyrosine if phenylalanine is available (an essential AA)
Describe AA made from a-ketoglutarate
A-ketoglutarate is first used to make glutamate which is non-essential and is the primary AA of this group. Glutamate is then used to make 3 conditionally essential AA- glutamine proline and arginine
Describe AA made from 3-phosphoglycerate
3-phosphoglycerate is first used to make serine which is non-essential and is the primary AA of this group. Serine is then used to make 2 conditionally essential AA- glycine and cysteine
__ require asparagine for growth
Malignant lymphocytes require asparagine for growth
Describe AA made from oxaloacetate
Oxaloacetate is first used to make aspartate which is non-essential and is the primary AA of this group. Aspartate is then used to make 1 non- essential AA- asparagine and 3 essential AA
Describe AA made from pyruvate
Pyruvate is used to make 1 non-essential AA- alanine and 3 essential AA
Tyrosine can be made if __ is available from diet
Tyrosine can be made if phenylalanine is available from diet
Describe AA synthesis form PEP
Phosphoenolpyruvate (PEP) together with erythrose 4-phosphate (intermediate in the pentose phosphate pathway and the Calvin cycle) can be used to make 3 essential AA, one of which is phenylalanine, which can be used to make tyrosine
Is pentose phosphate pathway important for AA synthesis in mammals? WHy?
Pentose phosphate pathway is not important for AA synthesis in mammals
Ribose 5-phosphate made in the pentose phosphate is a precursor of histidine which is an essential AA thus it cannot be made in mammals
What is the most important derivative of AA
Heme
How’s heme made?
Heme is synthesized from glycine in mammals.
Glycine is the precursor and is first converted into 𝛿-aminolevulinate
8 of 𝛿-aminolevulinate are put together into ring structures called porphyrins
When one of porphyrins intermediates -protophyrin intermediate receives iron it becomes heme
what is porphyria diseases
Accumulation of porphyrin intermediates
what is Jaundice
Accumulation of bilirubin
Disease of the liver- problem with bilirubin metabolism
If new born have it- no worry
How’s heme converted to bilirubin
The first step catalyzed by heme oxygenase, converts heme to biliverdin
Biliverdin is converted to bilirubin by biliverdin reductase enzyme
How’s bilirubin excreted?
Bilirubin is taken up by the liver which can convert it to bilirubin diglucuronide intermediate using bilirubin transferase enzyme
This intermediate is converted into bilirubin that goes into bile -> intestine
When bilirubin comes to intestine, bacteria is needed to convert it into urobilinogen
Urobilinogen is primarily converted into urobilin in kidneys
Urobilinogen has to be transported to the kidneys
Some of urobilinogen is also converted to stercobilin which is excreted through feces
__ gives color to urine
Urobilin gives color to urine
Explain color transitions of the bruise
Bruise= metabolism of heme
RBC come out, die and heme is released which is red -red, pink
With time, oxygen is released red to blue color change
That heme is slowly metabolized to biliverdin which has green color
It is then converted to bilirubin -> yellow color
What’s creatine made from?
Glycine, Arginine and Methionine
What and how is creatine is tuned into? Why is that compound important?
Creatine kinase phosphorylates creatine to make phosphocreatine
Phosphocreatine stores phosphate group that is necessary for ADP to ATP conversion -plays a role in ATP synthesis
Creatine is an __ derivative
Creatine is an amino acid derivative
what is glutathione made from?
Glutathione is synthesized from Glutamate, Cysteine and Glycine
Why is glutathione important?
- Glutathione is the major anti- oxidant
- Glutathione peroxidase dimerizes glutathione
to oxidized form which prevents oxidative damage
Glutathione is a derivative of __
Glutathione is a derivative of AA
Name neurotransmitters that are AA derivateives
Epinephrine
GABA
Histamine
Serotonin
Describe Epinephrine
Epinephrine - made from tyrosine. Flight or fight hormone
Describe GABA
- GABA- made from glutamate. It is mainly an inhibitory neurotransmitter in CNS, but is also important in maintaining muscle tone
Describe Histamine
- Histamine- made from histidine (it is essential AA). Plays a role in allergic acid and stimulated HCl release in stomach - important in digestion
Describe Serotonin
Serotonin- derived from tryptophan, an essential AA. Also plays a role in peristaltic movement in s intestine. Happiness and bonding hormone,
Name 5 reasons why are nucleotides important (what do they serve as)
- Precursors of nucleic acids
- Carriers of energy (ATP and GTP)
- Components of cofactors (NAD, FAD, CoA)
- Initiators of glycogenesis - UDP glucose
- Second messengers
What are nucleotides composed of
Base+ pentose sugar + phosphate group
What are nuclosides composed of
Base+ pentose sugar
Describe and name purines
Purines have 2 carbon-nitrogen rings
Guanine and Adenine
Describe and name pyrimidines
Pyrimidines- 1 carbon-nitrogen ring
Uracil, guanine and thymine
Nucleotide polymers have a __ ring
Nucleotide polymers have a 3’ an 5’ ring
Name 2 types of Nucleotides synthesis pathways
De novo
Salvage pathway
Describe Salvage pathway
purine/pyrimidine bases released from degradation of nucleotides
Describe de Novo pathway
Nucleotides are made from metabolic precursors (AA, ribose 5-phosphate, CO2 and NH3)
Are purine/pyrimidine bases synthesized as independent molecules (such as Glucose or FA)?
purine/pyrimidine bases are NOT synthesized as independent molecules (such as Glucose or FA)
What are purine rings built on and what need to be available?
Purine rings are built up on ribose phosphate
Sugar needs to be available for synthesis to occur
How are pyrimidine rings synthesized?
Pyrimidine ring is first synthesized as “orotate”
and then attached to ribose phosphate
How is nucleotide synthesis stimulated to continue?
Nucleotide pools are kept low, so cells must continually synthesize them
Describe PRPP
5-phosphoribosyl 1-pyrophosphate (PRPP) comes from ribose 5-phosphate (end product of pentose phosphate pathway)
It is one of the precursors for nucleotide synthesis
What’s the breakdown product of bilirubin?
Urobilinogen
What are the precursors for nucleotide synthesis?
5-phosphoribosyl 1-pyrophosphate (PRPP)
There are multiple AA that act as precursor for purines and pyrimidines
Which AA are precursors for which nucleotides?
Aspartate is the primary precursor for pyrimidines, glycine for purines
Glutamine provides the amino group for both
What is the first intermediate with a complete purine ring in de novo synthesis?
IMP- inosinate
What can Inosinate be used for?
Inosinate can then be converted to other purines in the form of AMP and GMP
Inosinate is a product of many reactions of __
Inosinate is a product of many reactions of PRPP
Which aa react in a serial order to make nitrogenous base in the form of inosinat?
Glutamine
Glycine
Glutamine
Aspartate
What is the difference between GMP and AMP made from Inosinate
AMP is oxidized at 6th carbon where it has a double bond and NH2
GMP is oxidized at the 2nd carbon where it has a double bond and NH2
What are the 2 types of inhibition of de novo synthesis
overall and specific inhibition
Describe overall inhibition of de novo
When the enzymes above IMP are inhibited - overall inhibition
One end product inhibits the production of both end products
ribose 5-phosphate
PRPP
5-phosphoribosylamine
Describe specific inhibition of de novo
One product inhibits the production of one product only
AMP inhibits AMP
GMP inhibits GMP
pyrimidine is constructed from __ and __
pyrimidine is constructed from carbamoyl phosphate and aspartate
Short summary of how pyrimidines are made
the six-membered pyrimidine ring is made first
and then attached to ribose 5-phosphate
Which enzyme is required in pyrimidine synthesis?
Cytoplasmic carbamoyl phosphate synthase II
Describe step of pyrimidine synthesis
Carbamoyl phosphate reacts with aspartate (precursors for De novo synthesis of pyrimidines)
It first has to be converted to Orotate
Once orotate is formed, the ribose 5-phosphate
side chain, provided once again by PRPP, is attached to
yield orotidylate
Eventually uridine 5’-triphosphate is formed (UTP) which is then converted into Cytidine 5’-triphosphate
How’s uridine 5’-triphosphate converted into Cytidine 5’-triphosphate
By adding a nitrogen group donated by glutamien to 4th carbon
Why is Pentose phosphate pathway important for nucleotide synthesis
- Provides hydrogen source in form of NADH
Provides precursor 5-phosphoribosyl 1-pyrophosphate (PRPP)
Hydrogen atoms required for reduction to “deoxy” form are donated by __
Hydrogen atoms required for reduction to “deoxy” form are donated by NADPH
How’s deoxyribose made?
Source of hydrogen are enzymatic reactions - glutathione reductase mechanism where hydrogen source is NADPH
NADPH comes from pentose phosphate pathway “OH” is replaced by “H” at 2nd Carbon of the ribose sugar
What has to be done first in order to produce deoxynucleotides
Deoxynucleotides are converted from ribonucleotides, so ribonucleotides have to be built first to then be converted to deoxynucleotides
How;s thymidine made?
Thymidine is made form UMP and CDP
The only difference between uracil and thymidine is the uracil group
UTP is the primary nucleotide that’s synthesized which is converted to UMP and TMP
Name overall inhibitors of de novo synthesis
ADP
AMP
GMP
IMP
