Synthesis of AA + their derivatives

Question 1

5 characetristics of overview AA synthesis

Answer 1

1. All AA can be derived from intermediates of metabolic pathway (ex: pyruvate, PEP, a-ketoglutarate, oxaloacetate, ribose-5-phosphate, erythrose 4-phosphate, 3-phosphoglycerate
   
   2. Bacteria and plants synthesize all of them
   3. Mammals synthesize 10 AA from intermediates of metabolic pathways
   4. Source of amino group: glutamine and glutamate
      Essential AA (9)

Question 2

9 essential AA, + 21st and 22st AA + what is non standard AA

Answer 2

• non-standard AA (not protein coding)
  ex: GABA, homocystein
• 21st AA : selenocysteine which is synthesize on tRNA and it is coded by UGA in context dependent manner
  ex: glutathione peroxidase
• 22nd AA: pyrrolysine (found in bacteria)
• 9essentials:
  
  1. Valine
  2. Phenylalanine
  3. Histidine
  4. Leucine
  5. Methionine
  6. Threonine
  7. Isoleucine
  8. Tryptophan
     lysine

Question 3

AA from a-ketoglutarate, 3-phosphoglycerate, pyruvate, oxaloacetate, PEP, ribose-5 phosphate

Answer 3

1. a-ketoglutarate : produces glutamate which will produce glutamine, proline and arginine but these are three conditionnaly essential AA (machineries that are not that efficient)
2. 3-phosphoglycerate: produces serine which will produce glycine and cysteine (2 conditionnally essential AA)
3. oxaloacetate: aspartate which will produce asparagine and also 3 essential AA (cant produce in the mammalian cells) which are methionine, lysine and threonine
   * * malignant lymphocytes (a cancer cell) require asparagine for growth so an enzyme that inhibits the conversion of aspartate to asparagine
4. pyruvate: alanine and 3 essential AA : valine, leucine, isoleucine
5. PEP + erythrose 4-phosphate: 3 essential AA: phenylalanine, tyrosine and tryptophan
   * ** particularity with tyrosine and phenylalanine: Tyrosine can be synthesized by converting phenylalanine so it can be essential or non-essential because its precursor is an AA so tyrosine is the 20th AA (10 nonessential, 9 essential)
6. ribose 5-phosphate (from pentose phosphate pathway) : esential AA = histidine, so this pentose pathway is not important for AA synthesis in mammals!!!

Question 4

resume of 9 essential, 5 non-essential and 6 conditionnaly essential

Answer 4

• 9 essentials:
  1. Valine
  2. Phenylalanine
  3. Histidine
  4. Leucine
  5. Methionine
  6. Threonine
  7. Isoleucine
  8. Tryptophan
  9. lysine
• 5 non-essential:
  1. alanine
  2. asparagine
  3. aspartate
  4. glutamate
  5. serine
• 6 conditionnaly essential
  1. arginine
  2. cysteine
  3. glutamine
  4. glycine
  5. proline
  6. tyrosine

Question 5

steps for heme by glycine

Answer 5

*** glycine is the precursor of heme proteins
step 1: formation of aminolevulinate
- glycine reacts with succinyl-coa which will form intermediate to finally produce aminolevulinate
step 2: formation of heme
- 8 aminolevulinates are put together in a ring structure which is called porphyrins. The inermediate porhpyrin, when it releases iron, becomes heme

** accumulation of porphyrin intermediates = porphyria diseases

Question 6

steps for the bile pigments from heme

Answer 6

1. Heme to biliverdin (by the enzyme heme oxygenase)
   
   2. Biliverdin to bilirubin (by the enzyme biliverdin reductase)
   3. Bilirubin (in blood) is converted to bilirubin diglucuronide ( by the enzyme glucuronyl-biribulin transferase in the liver)
   4. Biribulin diglucuronide i transport to intestine where it becomes biribulin (in bile)
   5. Biribulin is convert to urobillinogen by bacteria
   6. Urobillinogen has 2 options:
      - It is transported to the kidney and becomes urobillinogen which will become urobilin
      - It is convert to stercobilin bu bacteria

** accumulation of bilirubin - jaundice (increase of nilirubin the blood)

**
Bruces are the metabolsim of heme: small vessels break, RBC comes out and dead which release heme and oxygen contain in it will be release and it will pass from red to blue (biliverdin has a green color and bilirubin = yellow) so until all the mechanisms are resolve, there will be a color

Question 7

biosynthesis of creatine and phosphocreatine

Answer 7

Creatine is from glycine, arginine, and methionine
Phosphorylated by creatine kinase to phosphocreatine which stores phosphate group for ATP synthesis (buffer for muscular ATP)

Question 8

biosynthesis and oxidation of glutathione

Answer 8

• Glutathione is synthesized from glutamate, cysteine and glycine
  
  • Glutathione is the major antioxidant
  • Glutathione peroxidase dimerizes to oxidized form
    Prevents oxidative damage

Question 9

4 neurotransmitters from AA

Answer 9

1. Epinephrine is synthesized from tyrosine
   
   2. GABA synthesize from glutamate= inhibitory neuraltransmitters in the nervous system and mainatin muscle tone
   3. Histamine derived from histidine (esssential AA) : plays a role in allergy reaction + stimulates HCl in the stomach so important for digestion
      Serotonin derived from tryptophan (essential AA) : plays a role in peristaltism movement in digestion and fell-good hormone (when we are happy)

Question 10

5 reasons nucleotides are important

Answer 10

1. Precursors of nucleic acids
   
   2. Carriers of energy (ATP and GTP)
   3. Components of cofactors (NAD, FAD, CoA)
   4. Initiators of glycogenesis
2. Second messengers (cyclic AMP)

Question 11

4 characteristics of nucleotide synthesis

Answer 11

• 2 types of pathways:
  
  1. De novo pathway: metabolic precursors (AA, ribose 5-phosphate, CO2 and NH3)
  2. Salvage pathway : purine/pyrimidine bases released from degradation of nucleotides
     - Purine/pyrimidine bases are NOT synthesized as independent molecules suc as glucose or FA:
  3. Purine rings are built up on ribose phosphate
  4. Pyrimidine ring is first synthesized as orotate and then attached to ribose phosphate
     Nucleotide pools are kept low, so cells must continually synthesize them

Question 12

precursors of nucleotides synthesis

Answer 12

• 5-phosphoribosyl 1-pyrophosphate (PRPP) which is synthesized from ribose 5-phosphate
• AA precursor for pyrimidines: aspartate
• AA precursor for purine: glycine
• amino group donor for both: glutamine

Question 13

de novo synthesis of purines

Answer 13

4 precursors: PRPP, glycine, glutamine, aspartate
** IMP is the first intermediate with a full purine ring
AMP:
1. Use aspartate and GTP with the enzyme adenylsuccinate synthetase to produce adenylosuccinate
2. Adenylosuccinate is converted to adenylate (AMP) by the enzyme adenylosuccinate lyase
** the amino group (NH2) is on the 6th carbon of the AMP

GMP:

1. Conversion of IMP to xanthylate by the enzyme IMP dehydrogenase and by the reduction of NAD+
2. Conversion of xanthylate to guanylate (GMP) by the enzyme XMP-glutamine amidotransferase + used of glutamine and ATP * * the amino group is on the 2nd carbon of GMP

Question 14

regulation of novo synthesis for purine

Answer 14

1. The enzyme glutamine-PRP amidotransferase is inhibited by the end products IMP, AMP, and GMP
   So when thre is an excess of the product, it inhibits it.
   
   2. An excess of GMP in the cells (at a later stage than the first recaction), GMP inhibits formation of xanthylate from inositate by IMP dehydrogenase, without affecting the formation of AMP!!!
   3. The accumulation of AMP inhibits formation of adenylosuccinate synthetase without affecting the production of GMP
   4. Inhibition of PRPP by ADP or GTP for the enzyme ribose phosphate pyrophosphokinase (PRPP synthetase)

Question 15

regulation of novo synthesis for pyrimidines

Answer 15

1. At first, need cytoplasmic carbamoyl phosphate synthetase II and Aspartate converts to orotate (with some intermediates)
   
   2. Orotate with PRPP is attached to a ribose sugar by the enzyme orotate phosphoribosyl-transferase
   3. uridine triphosphate is the first one to be synthesize from uridylate by the enzyme kinases qith the uses of ATP which is then converted to CTP by the enzyme cytidylate synthetase (with glutamine and ATP)
      * * the glutamine goes on the 4nd carbon of the pyrimidine)

** high quantity of CTP inhibits the first enzyme of the pathway which is aspartate trans-carbamoylase

Question 16

ribonucleotides to desoxyribonucleotides

Answer 16

Deoxy requires a pair of hydrogen atoms, which are ultimately donated by NADPH via an intermediate hydrogen-carrying protein, thioredoxin (ubiquitous protein that has pairs of SH that carry hydrogen atoms from NADPH to ribonucleoside diphosphate (enzyme= thoredoxin reductase).
A second source of reducing is glutathione (GSH) which serves as the reductant for the protein glutaredoxin which then transfer the reducing power to ribonucleotide reductase

** OH is replaced by H at the second carbon of the ribose sugar

Question 17

formation of thymine from cytosine and uracil

Answer 17

Thymine is from cytosine and uracil

1. CDP is converted to dCDP and UDP is converted to dUDP by ribonucletoide reductase
2. dCDP to dCTP and dUDP to dUTP by nucleosie diphosphate kinase
3. dCTP to dUTP by deaminase
4. dUTP to dUMP by dUTPase 5. dUMP to dTMP by thymidylate synthase