Part 3. Conversion of Amino Acids to Specialized Products

Question 1

What are porphyrins?

Answer 1

Cyclic compounds that bind primarily Fe2+ or Fe3+
Most common is heme (binds one Fe2+), heme is a prosthetic group for hemoglobin, cytochromes, and some enzymes

Porphyrins differ in their side chain

4 pyrrole rings linked together
all carbon and nitrogen atoms in their core structure are derived from glycine and succinyl CoA
Slide 3 Mar 18

Question 2

What is porphyrias?

2 types?

Answer 2

Rare generic disease which lead to defects in biosynthesis of porphyrins and accumulation of intermediates

Acute intermittent porphyria- most common, requires an environmental/nutritional insult

Porphyria cutanea tarda- red urine, teeth fluoresce strongly in ultraviolet light, skin abnormally sensitive to light, anemic due to insufficient heme (vampire myth)
Slide 6 Mar 18

Question 3

How is tyrosine converted to epinephrine? (Slide 7 Mar 18)

What are catecholamines?

Answer 3

Slide 7 Mar 18
Catecholamines- dopamine, norepinephrine, and epinephrine
Synthesized from tyrosine

Question 4

How is histidine converted to histamine? (Slide 8 March 18)

What is histamine?

Answer 4

Histamine- a molecule that mediated many responses (allergic and inflammatory responses, gastric acid secretion)
Strong vasodilator
Formed from decarboxylation of histidine

Question 5

How is tryptophan converted to melatonin? (Slide 9 Mar 18)

What is serotonin (5-hydroxytryptamine)?

Answer 5

Serotonin (5-hydroxytryptamine)- found in abundance in intestinal mucosa, and lesser amounts in CNS where it functions as a neurotransmitter
Mediates pain perception, sleep, temp, blood pressure, appetite, sense of well-being (serotonin is converted to melatonin in brain, melatonin maintains circadian rhythm)

Question 6

What is creatine?

Slide 10 Mar 18

Answer 6

The phosphorylated form, creatine phosphate or phosphocreatine, is high energy compound found in muscle
Small pool of energy source (few minutes worth), but is readily available to replenish ATP levels by transferring its phosphate group to ADP
synthesized from glycine, guanidino group of arginine

Glycine reacts with arginine (provides most of backbone), methionine provides methyl group that is required

Slide 10 Mar 18

Question 7

What is monosodium glutamate (MSG) and the Chinese restaurant syndrome?

Answer 7

On average we consume 13g if glutamate from protein sources, and 0.6g from MSG

Most of glutamate ingested is oxidized in the small intestine

1. Transport into epithelial cells
2. Glutamate acres upon by several transaminases and glutamate dehydrogenase; the product of both is α-ketoglutarate
3. α-ketoglutarate is oxidized by TCA cycle

Question 8

Why can different aminotransferases act on glutamate?

Answer 8

Because they are specific for the α-keto acid and amino acid pair, not glutamate or α-ketoglutarate

Slide 12 Mar 18

Question 9

What is the nitrogen cycle?

Answer 9

Slide 15 Mar 18
Nitrogen is assimilated to biomolecules
Ammonium and nitrates are forms of nitrogen that are available to plants
Nitrates are reduced to ammonium
Nitrates are most common form of nitrogen that plants take up, plants reduce this to ammonium very quick

Question 10

What is the nitrogenase complex?

Answer 10

Slide 17 Mar 18

Electrons from reduced ferredoxin go into reductase (Fe protein) and go to nitrogenase (MoFe protein) by ATP

Question 11

What is the date of ammonia produced by nitrogenase complex?

Answer 11

The ammonia produced in root nodules in leguminous plants is directly used by the plant
The ammonia produced by nitrogen-fixing microorganisms in the soil is converted to nitrite and then to nitrate by other bacteria. Nitrate (NO3) is taken up by plants, and reduced to NH3

Question 12

What are glutamate and glutamines roles in assimilation if ammonia to biomolecules?
What are the 3 enzymes from these two?

Answer 12

Glutamate and glutamine provide entry points to assimilation if ammonia to biomolecules
(First two important molecules to which free ammonia is assimilated)

Glutamate dehydrogenase
Glutamine synthetase
Glutamate synthase

Slide 19 Mar 18

Question 13

What’s the different between glutamate and glutamine is how they funnel ammonia?

Answer 13

Glutamate- contributes alpha amino group (ammonia group)

Glutamine- has its alpha amino group to donate as well as its terminal chain, so it donates its side chain not its alpha
Source of amino group in many biosynthetic processes

Question 14

What are the 3 amino acid/keto-acid pairings?

Answer 14

Slides 20-21 Mar 18

Amino-transferase
Alanine transaminase (ALT)
Aspartate transaminase (AST)

Question 15

How are the carbon skeletons for amino acid synthesis provided?

Answer 15

The carbon skeletons for amino acid synthesis are provided by intermediated of the glycolytic pathway, the citric acid cycle, and the pentode phosphate pathway

Slide 23-24 Mar 18

Question 16

What is glutamine synthetase and it’s job?

How is it regulated?

Answer 16

Converts glutamate to glutamine
Glutamine synthetase is present in all organisms
Primary regulatory point in nitrogen metabolism (glutamine is source of amino group in many biosynthetic processes)
No activators

Regulated by:

1. Allosteric effectors (8 of them) combined effect of all 6 end product inhibitors is more than additive (every inhibitor has a nitrogen group)
2. Covalent modification - adenylylation (addition of AMP) inhibits the enzyme by making enzyme more sensitive to inhibitors

Slide 6 Mar 20
Structure slide 8 Mar 20

Question 17

What is adenylylation?

Answer 17

Occurs on Tyr residue
ATP cuts and creates PPi

Slide 7 Mar 20

Question 18

What are the 3 important reaction in amino acid and nucleotide synthesis?

Answer 18

1. Transamination reaction
   Enzyme: aminotransferase
   Coenzyme: pyridoxal phosphate (vit B6)
2. 1-carbon transfer reactions
   Enzyme co factors: S-adenosyl methionine (Sam)- donates methyl group, tetrahydrofolate (TH4)
   Methyl group usually transfers to a nitrogen or oxygen atom
   Slide 10-14 Mar 20
3. transfer if an amino or snide group from glutamine
   Slide 15 mar 20

Question 19

What intermediates are used to synthesize amino acids?

Answer 19

Specific intermediates from the glycolytic, pentode phosphate, and TCA cycle

Amino acids must be synthesized in the correct amounts at the right time for protein synthesis

Mammals can only synthesize the non essential amino acids. The essential amino acids are supplied in the diet (most bacteria and plants can synthesize all 20 amino acids)

Question 20

Study the essential and non essential amino acids on slide 19 Mar 18

Answer 20

Okay

Question 21

What amino acids are from oxaloacetate?

What one are from pyruvate?

Answer 21

Oxaloacetate- first goes to aspartate then that can be converted to asparagine, methionine, lysine, and threonine
Lots of reactions must occur between these
Slide 21 Mar 18

Pyruvate- can be converted to alanine, valine, leucine, or isoleucine

Slide 20 mar 18

Question 22

What are the 4 types of feedback inhibition?

Answer 22

Product inhibition
Sequential
Concerted
Enzyme multiplicity

Slide 2-3 Mar 22