Overview Of Nitrogen Metabolism

Front 1

How many electrons and ATP molecules are needed to reduce atmospheric nitrogen?

Back 1

8 electrons and 16 ATP

Front 2

Name the enzyme that catalyzes the reductive amination reaction of ∂-ketoglutamate to glutamate (and its reverse rxn)? Besides the enzyme, what else is required for this reaction?

Back 2

a) Glutamate dehydrogenase… b) NH4 + NADH or NADPH

Front 3

a) Name the enzyme that catalyzes the reductive amidation reaction of the carboxylate group of glutamate to produce glutamine (and its reverse rxn)?

b) What else is required for this rxn?

c) Why is glutamate considered a "gateway molecules"?

d) besides NAD/NADH, what can be used to reduce ∂-KG?

e) what is the take home message of showing the "glutamate dehydrogenase" and the "glutamate synthase" reactions?

Back 3

a) glutamine synthetase…

b) NH4 + ATP

c) Glutamate's ∂-amino can be tranfered to become the ∂-amino of another amino acid.

d) NADPH

e) these rxns show how nitrogen (in the form of amonia/amonium) can enter biologic systems

Hint 3

None

Front 4

Is glutamine found in great or small concentration in the blood?

Back 4

great

Front 5

Main Scheme of AA metabolism:

a) what are the three fates of amino acids taken into a cell from the blood stream?

b) What is the first step in catabolism of amino acids?

Back 5

a) AA -->
1) Proteins,
2) N- containing molecules (nucleotides),
3) catabolism.

b) removal of the nitrogen

Hint 5

None

Front 6

Name the essential amino acids. (hint: TV PHaT MILL)

Back 6

threonine, valine, phenylalanine, histadine, arginine (in young), tryptophan, methionine, isoleucine, leucine, lysine

Hint 6

None

Front 7

What are the 3 amino acids generally lacking in plants?

Back 7

Lys, Met, Trp

Front 8

(a) what is the problem of having a narrow protein source?

b) Why does a high gelatin diet deplete Met?

Back 8

(a) Because each source offers its own set of amino acid, and having multiple sources guarantees that you will get a variety of amino acids.

b) Gelatin lacks cysteine, so the body will synthesize it... the problem is that cysteine synthesis requires Met, thus a high gelatin diet will deplete Met

Front 9

Give 3 advantages to amino acid turnover.

Back 9

1) quality control of proteins… 2) provides continuous supply of amino acids that may be in more demand… 3) metabolic control.

Front 10

a) Where does most protein turnover occur?

b) do most amino acids come from dietary sources or protein turnover?

Back 10

a) digestive enzymes, sloughed off intestinal cells, skeletal muscle

b) protein turnover

Hint 10

None

Front 11

a) How does turnover play an important role in metabolic control?

b) Should a highly controlled metabolic process have enzymes with a long or short half life?

Back 11

a) Turnover plays a regulatory role by adjusting the amounts of key enzymes by altering their synthesis and degradation rates

b) short - the half-life length is a tighter regulation of the enzyme

Front 12

Assign values to the following?

Additions:
- Dietary protein
- Amino acids released from protein turnover

Subtractions:
- Amino acids used for protein synthesis
- Amino acids catabolized/excreted

Total amino acid mass gained/lost =

Total body amino acid pool=

Body mass of protein =

Back 12

Assign values to the following?

Additions:
- Dietary protein = 100g
- Amino acids released from protein turnover = 300g

Subtractions:
- Amino acids used for protein synthesis = 300g
- Amino acids catabolized/excreted = 100g

Total amino acid mass gained/lost = 0g

Total body amino acid pool= 100g

Body mass of protein = 12,000g

Front 13

Describe Positive Nitrogen Balance

Back 13

a scenario where amino acid dietary input (to tissue protein) exceeds the sum of excretion and production of nitrogen containing molecules (purines, hemes, etc.)

Hint 13

None

Front 14

a) what can have the biggest effect on the body's total amino acid pool, dietary intake or the percentage or the changes in the percent change of body mass protein?

b) What is the average body mass of protein in grams?

Back 14

a) percent change of body mass protein.

b) 12000 g

Hint 14

None

Front 15

What kind nitrogen balance will a person who is undergoing growth, pregnancy, lactation, recovery from physiologic stress? Describe this state.

Back 15

Positive Nitrogen Balance: greater dietary protein input than excretion.

Front 16

What kind nitrogen balance will a person who is undergoing surgery, trauma, burns, physiologic stress? Describe this state.

Back 16

Negative Nitrogen Balance: greater tissue breakdown and excretion than than dietary input.

Front 17

a) What kind nitrogen balance will a person who is receiving inadequate dietary input? (Kwashiorkor) Describe this state.

b) When is Kwashiorkor seen and

c) What causes Kwashiorkor effects?

d) what precipitates the negative nitrogen balance seen in Kwashiorkor?

Back 17

Negative Nitrogen Balance: inadequate input, with tissue protein being used to supply amino acid pool and basic production N-containing molecules, where excretion is larger than dietary input.

b) it's seen in children in developing countries as they wean from breast milk to diets high in carbohydrates

c) Muscle wasting and distended abdomen may be due to a lack of serum proteins that cause edema

d) infection or starvation: "Maramus" = low protein, high carbohydrates.

Hint 17

None

Front 18

What kind nitrogen balance will a person who is lacking in one amino acid? Describe this state.

Back 18

Negative Nitrogen Balance: tissue breakdown results to synthesize the needed amino acid... and the input is equal to the excretion... but the tissue proteins are being slowly depleted to produce the deficient amino acid.

Hint 18

None

Front 19

1. Describe the gamma-glutamyl cycle that allow amino acid membrane transport.

2. Which enzyme is needed to release the amino acid from gamma-glu?

2. Does a deficiency in a major proteolytic enzyme have a general effect, or specific on the types of amino acids yielded?

Back 19

1. Amino acid is transported across the membrane by glutathione > then cysteinylglycine is removed leaving a glutamyl-AA > the amino acid leaves, leaving 5-oxoproline, while cysteinylglycine converts to cystein and glycine > (add ATP converts 5-oxyproline to...) > glutamate (add ATP to add cystein to glutamate) > gamma-glutamylcysteine (add ATP to add glycine) > glutathionine is now recycled.

2. 5-oxyprolinase

3. Somwhat specific, since the enzymes will have lytic activities only on certain residues.

Front 20

1. What is the major enzyme involved in the activation of other proteolytic enzymes (zymogens)?

2. Why are proteins digested in the gut?

3. How do amino acid membrane transporter found in the gut differ from those in the kidneys?

4. Which two amino transport systems aren't Na/K pump dependent?

5. Name the transport system:
a) basic amino acids, cystein
b) gluatamate, aspartate
c) neutral amino acids, especially branched chain and phenylalanine
d) neutral amino acids, especially serine, alanine and cysteine
e) glycine, proline, hyroxyproline
f) Histidine, asparagine, glutamine

(hint: Cationic, anionic, N, Gly, L, A, ASC)

Back 20

1. Trypsin

2. They are too large to be absorbed and must be digested to amino acid or small peptides (di or tripeptides) first

3. They don't

4. L and cationic

a) Cationic = basic amino acids, cystein
b) Anionic = gluatamate, aspartate
c) L = neutral amino acids, especially branched chain and phenylalanine
d) ASC = neutral amino acids, especially serine, alanine and cysteine
e) Gly = glycine, proline, hyroxyproline
f) N = Histidine, asparagine, glutamine

Hint 20

None

Front 21

1. How many ATP are needed to transport amino acids across the intestinal border?

2. How many ATP are needed to transport amino acids across the seosal side of the epithelial cell border?

3. Where else are amino acid transporters found?

4. What does BUN measure?

5. what is the clinical relevance to a high BUN?

6. How do you calculate the fraction of urea that is due to two nitrogen atoms?

Back 21

1. 1/3 ATP/amino acid

2. None, it follows its concentration gradient all the way to the portal vein to the liver. (this [gradient] can be reversed to send AA to epithelial cells during starvation)

3. Liver, muscle kidney (where amino acids are saved from excretion)

4. Blood urea nitrogen (mg/100 ml urea) it measures the concentration of nitrogen in the blood in the form of urea.

5. A high BUN implies tissue damage or poor kidney function

6. multiply by 0.5

Front 22

1. What is the source of the nitrogen found in uric acid?

2. ammonia is toxic in the blood, but what purpose does it serve in the urine?

Back 22

1. the breakdown of nucleic acids (adenine and guanine)

2. balance pH

Hint 22

None

Front 23

1. What is the major high energy phosphate donor in skeletal muscle?

2. what is its fate?

Back 23

1. creatine

2. creatine phosphate is cyclized to creatinine and excreted in the urine.

Hint 23

None

Front 24

1. What is the importance of creatinine?

2. why isn't creatinine reabsorbed?

Back 24

1. No physiologic usefulness, but it is used to normalize clearance of urinary solutes (an accurate measure of time during which urine was formed)

Note: creatine phosphate is a high energy phosphorylated moiety.

2. no transporters

Hint 24

None

Front 25

what does a high "absolute" value of creatinine blood level suggest?

Back 25

kidney filtration problems

Hint 25

None

Front 26

What is cystinuria?

Back 26

A urinary tract disease… an autosomal recessive disorder that results in the rise in cysteine (arginine, lysine and ornithine) in the urine due to a defective transporter… causes cystine stones

Front 27

What are 3 thing you can do to treat for cystinuria?

Back 27

a) hydration, b) increase urine alkalinity, c) thiol compounds which forms more soluble mixed disulfides.

Front 28

Name the 7 metabolites that amino acids are metabolized into.

Back 28

pyrvate, acetyl CoA, ∂-ketoglutamate, succinyl CoA, Fumarate, oxaloacetate, acetoacetate

Front 29

1. Which amino acids can be oxidized to produce energy or energy storage molecules?

2. Where do ketogenic amino acids funnel through?

3. where do glucogenic amino acids funnel through?

4. which 2 amino acids are strictly ketogenic amino acids?

Back 29

1. all 20 AA

2. Acetyl CoA, (--> acetoacetyl CoA-->) HMG-CoA --> Acetoacetyl CoA

3. Pyruvate to form glucose

Hint 29

None

Front 30

Give the pathway of pyruvate to glucogenesis.

a) intermediates
b) enzymes

Back 30

a) Pyruvate -(1)-> oxaloacetate -(2)-> PEP --> glucogenesis

b) 1= pyruvate carboxylase, 2= PEPCK

Hint 30

None

Front 31

NOTE: SKIP ALL THE FOLLOWING QUESTIONS FROM THIS POINT FORWARD:

Which amino acids funnel into ∂-KG? (hint: PHAG)

Back 31

proline, histadine, arginine, glutamine

Hint 31

None

Front 32

What do proline, histadine, arginine, and glutamine funnel into before entering into ∂-KG?

Back 32

glutamate

Front 33

Which amino acids funnel into succinyl CoA? [hint: I (want my) MTV... and "T" rhymes w/3]

Back 33

Isoleucine, methionine, threonine, valine

Front 34

Which intemediate must (Isoleucine, methionine, threonine, valine) funnel through before succinyl CoA?

Back 34

Propionyl CoA --> Methylmalonyl CoA --> Succinyl CoA

Front 35

Which amino acids funnel into fumarte? (hint: When you are "tired" you could use more ATP)

Back 35

Aspartate, tyrosine and phenylalanine

(explanation of hint: tired sounds like tyrosine)

Front 36

Which amino acids funnel into oxaloacetate? (hint: AA)

Back 36

aspartate and asparagine

Front 37

Which amino acids funnel into acetyl CoA? (hint: LITT)

Back 37

Lysine, Isoleusine, threonine, tryptophan

Front 38

What is the pathway for acetyl CoA to reach acetoacetate?

Back 38

Acetyl CoA --> Acetoacetyl CoA --> HMG CoA --> Acetoacetate (ketone Bodies)

Front 39

What is significant about acetoacetate?

Back 39

Ketone bodies

Front 40

Besides (Lysine, Isoleusine, threonine, tryptophan) what 3 other amino acids can funnel into the acetoacetate (ketone body)? (Think ringed AA for two of them)

Back 40

Leucine and phenylalanine, tryosine.

Front 41

(a) Which two amino acids are considered ketogenic amino acids?

(b) What are the other amino acids considered?

(Hint:Lucy Lu KiLLed biLL w/ Keto)

Back 41

(a) leucine and lysine…

b) the others are considered glucogenic amino acids.

(Eplanatin of hint: LL = keto)

Front 42

What is the pathway for pyruvate or oxaloacetate to enter the glucogenic pathway?

Back 42

Pyruvate (with pyrvuate carboxylase) --> oxaloacetae (with PEPCK) --> PEP --> glucogenesis