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Flashcards in Metabolism 10 Deck (28):
1

Describe three ways free amino acids in the body are derived.

1) degradation of ingested protein

2) biosynthesis of some of the amino acids

3) degradation of endogenous protein.

2

Draw an overview of amino acid metabolism.

p 3
Slide 2

3

Describe 3 ways free amino acids are used.

1. resynthesis of endogenous protein
2. precursors for synthesis of other biomolecules
3. for energy production (the amino group is excreted as urea in the process)

4

Describe the biosynthesis of amino acids.

Describe non-essential vs essential aa.

What can a deficiency of essential amino acids lead to in children and adults?

About half of the amino acids can be synthesized in the body from precursor molecules; these are
referred to as “nutritionally non-essential” amino acids. The remaining amino acids must be
supplied in the diet and are therefore called “nutritionally essential” amino acids. Since the
synthesis of most proteins requires all of the amino acids, a deficiency of an essential amino acid
in the diet can retard growth in children and lead to loss of body protein in adults.

5

List the essential and non-essential amino acids.

Essential Nonessential
Arginine Alanine
Histidine Asparagine
Isoleucine Aspartate
Leucine Cysteine
Lysine Glutamate
Methionine Glutamine
Phenylalanine Glycine
Threonine Proline
Tryptophan Serine
Valine Tyrosine

(All hideous iguanas like licking moldy pizza, then they vomit)

6

Cells contain a large number of different proteolytic enzymes (peptidases) in various cellular
compartments that are responsible for degrading endogenous proteins to free amino acids. What are the two
primary pathways for protein degradation?

ATP-dependent ubiquitin-proteosome system

the lysosomal pathway.

7

About how much of total body protein in adults is degraded and resynthesized a day? What happens to excess amino acids?

How many grams of protein does the body degrade or otherwise lose per day? How is this loss replaced?

Adults degrade and resynthesize 2-3% (approx 300 g) of their total body protein every day (see
figure below). Although there is a small transient storage of protein after a meal and degradation
between meals, there is no net accumulation of protein even on a high protein diet. Excess
amino acids are degraded, not stored.

Part of the pool of free amino acids is always being catabolized. This amino acid degradation
occurs even if no protein is being supplied in the diet, i.e., it is required or “obligatory.” The
body degrades or otherwise loses the equivalent of at least 55 g of protein every day (for a 70-kg adult). This loss must be replaced by dietary protein.

8

At what daily protein intake will a loss of body protein occur? (What is the recommended dietary allowance?

What would happen if intake exceeds this value?

A daily protein intake of less than 55 g (per 70 kg body weight) will result in loss of body protein.

This value therefore represents the Recommended Dietary Allowance (0.79 g/kg). If
protein intake is greater than 55 g, the excess amino acids are degraded, not stored.

9

A normal adult is typically in nitrogen equilibrium. What does this mean?

Nitrogen balance = nitrogen ingested (primarily as protein) - nitrogen excreted (primarily as urea)

(nitrogen balance = 0). In this state, the rate
of protein synthesis equals the rate of protein degradation, and the amount of nitrogen taken in as dietary protein is balanced by excretion of nitrogen as urea (from amino acid catabolism).

10

Describe a positive nitrogen balance. In what physiological states might this occur? What will occur?

In certain physiological states, e.g., growth in children, pregnancy, and bodybuilding, the amount
of nitrogen ingested is greater than the amount of nitrogen excreted (positive nitrogen balance).
In these cases, protein synthesis occurs at a slightly higher rate than protein degradation, and
nitrogen accumulates.

11

Describe a negative nitrogen balance. In what physiological states might this occur? What will occur?

In conditions of starvation, protein malnutrition (with otherwise adequate calories), trauma,
infection, cancer, burn injury, sepsis, and surgery, the amount of nitrogen ingested is less than
that excreted (negative nitrogen balance). In these cases, the rate of protein synthesis is less than the rate of protein degradation, and muscle mass will therefore decrease.

12

Describe the biosynthesis of urea.

Where does urea biosynthesis and excretion occur?

Draw a summary of the fate of the amino nitrogen atom of amino acids.

The amino group of amino acids is incorporated into the molecule urea and excreted.

Urea biosynthesis occurs in the liver. Urea is excreted primarily by the kidney.

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13

What is transamination?

What form are most amino acids collected in?

A step in the degradation of most amino acids is transamination, the transfer of the amino group to alpha-ketoglutarate to form glutamate.

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There are several different amino acid transaminases (aminotransferases) that act on specific amino acids. All of them use α-ketoglutarate as the amino group acceptor to
form glutamate. Therefore, the amino groups from most of the amino acids are
collected in the form of glutamate.

14

What is the cofactor required for transaminases?

pyridoxal phosphate (active derivative of Vit. B6)

15

Where are transaminases usually located? How much is present in serum?

Describe what will happen in hepatitis.

Transaminases
are cytosolic enzymes, and the amount measured in serum is normally low.

During tissue
damage (e.g., hepatitis), cells necrose and release cytosolic enzymes (including transaminases) into the blood. Laboratory results that indicate increases in the serum
activities of the two transaminases can assist in diagnosis. (Alanine transaminase and aspartate transaminase)

16

Two transaminases (aminotransferases) are important in clinical diagnosis. Transaminases
are cytosolic enzymes, and the amount measured in serum is normally low. During tissue damage (e.g., hepatitis), cells necrose and release cytosolic enzymes (including transaminases) into the blood. Laboratory results that indicate increases in the serum
activities of the two transaminases can assist in diagnosis. What are they?

1) Alanine transaminase (ALT, SGPT, GPT): serum activity is increased in hepatitis, cirrhosis,
liver metastases, obstructive jaundice, infectious mononucleosis, pancreatitis, renal disease, alcohol ingestion.

2) Aspartate transaminase (AST, SGOT, GOT): serum activity is increased in liver disease, heart failure, myocarditis, pericarditis, myositis, muscular dystrophy, trauma, pancreatitis, renal
infarct, eclampsia, neoplasia, cerebral damage, seizures, hemolysis, alcohol ingestion.

17

What provides the nitrogen atoms that are incorporated into urea? What is their precursor?

As shown in SUMMARY FIGURE 2, aspartate and ammonia provide the nitrogen atoms that are incorporated into urea. Both aspartate and ammonia are formed from
glutamate (which contains the nitrogen from various amino acids via transaminase reactions).

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18

What enzymes are important for the formation of asparate and ammonia from glutamate?

glutamate and oxaloacetate (asparate transaminase) gives you alpha ketoglutarate and asparate

glutamate + NAD(P)+ + H2O (glutamate dehydrogenase) gives ammonia and alpha ketoglutarate and NADPH
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19

What is the reaction for synthesis of urea from ammonia and asparate?

aspartate + NH3 + CO2 + 3ATP + 3H2O to urea + fumarate + 2ADP + AMP + 4 Pi

20

Draw a summary figure of the urea cycle.

p 10

21

Describe the subcellular location of urea cycle enzymes:

Where does the syntheses of carbamoyl phosphate and citrulline take place? What about the rest?

The syntheses of carbamoyl phosphate and citrulline take place in the mitochondria.
Other reactions are in the cytosol.

Ornithine and citrulline enter and leave the mitochondria, respectively, via an exchange transporter.

22

What activates the enzyme that makes carbamoyl phosphate?

How will increased levels of glutamate affect this molecule? What results?

What will long exposure to high protein diet or high rate of protein degradation lead to?

N-Acetylglutamate activates the enzyme that makes carbamoyl phosphate
(carbamoyl phosphate synthetase I). Increased levels of glutamate (e.g., from
transamination of amino acids from dietary protein) lead to increased levels of N-acetylglutamate and therefore stimulation of urea production.

Long-term exposure to a high protein diet or to a high rate of protein degradation
leads to increased levels of urea cycle enzymes.

23

Urea is synthesized in the liver. However, amino acid metabolism also occurs in
tissues other than liver (e.g., muscle). Therefore, the nitrogen must be transferred to liver for conversion to urea. What are the main carriers?

Urea is synthesized in the liver. However, amino acid metabolism also occurs in
tissues other than liver (e.g., muscle). Therefore, the nitrogen must be transferred to liver for conversion to urea.

Alanine (via the alanine-glucose cycle) and glutamine
are the main carriers of nitrogen to the liver. These two are present in blood at higher concentrations than other amino acids.

24

What is normal BUN? How is this value diagnostically useful?

The plasma urea concentration is reported by clinical laboratories as BUN (normal: 7-30 mg/dL). BUN is diagnostically useful: (Increased in renal disease, dehydration, GI bleeding, leukemia, heart failure, shock, urinary tract obstruction, acute MI. Decreased in liver failure,
overhydration, pregnancy, acromegaly.)

25

The function of urea biosynthesis is the detoxification of ammonia.

Ammonia at too high of a concentration (hyperammonenia) predisposes to coma.

What can cause hepatic coma?

Hepatic coma results from decreased capacity of the liver to remove ammonia via
urea production; this can be due to acquired or genetic factors:

a. Acquired hyperammonemia:
This can result from portal-systemic-shunting, i.e., diversion of blood flow
around the liver in response to cirrhosis. Ammonia produced by bacteria
in the intestine is absorbed, but it is not converted to urea in the liver. The
resulting hyperammonemia causes “portal-systemic encephalopathy.”

b. Genetic hyperammonemia:
Deficiency of a urea cycle enzyme

26

Describe the fate of carbon skeletons. What are they used for?

Describe the 2 types (which amino acids fit into each category/both)

The carbon skeletons are used for energy.

Amino acids can be classified on the basis of whether they
are glucogenic or ketogenic:

Glucogenic: yields TCA cycle intermediate(s) or pyruvate
that can be used for gluconeogenesis.

Ketogenic: yields acetyl CoA , acetoacetyl CoA, or
acetoacetate.

Ketogenic-Leu, Lys
Glucogenic/Ketogenic: Isoleucine, Phe, Thr, Try, Tyr

Glucogenic: Ala, Arn, Arg, Asp, Cys, Glu, Gln, Gly, His, Hydroxyproline, Met, Pro, Ser, Val

27

Following a meal, about one third of the newly absorbed amino acids are transiently
stored as protein in several tissues (the remaining two thirds are degraded immediately). In muscle, what causes this transient storage?

What happens during overnight fast?

this transient storage is caused by stimulation of protein synthesis (by amino acids and
insulin) and by inhibition of protein degradation (insulin).

During an overnight fast, the decrease in plasma amino acids and insulin leads to net protein degradation and release of amino acids for use by liver for gluconeogenesis.

28

Can you use acetyl-CoA to make glucose? Why/Why not?

acetyl-CoA cannot be used to make glucose. acetyl group has 2 C …will be removed as CO2 through cycle. provides energy for gluconeogenesis but in itself is not used to make glucose

when u use citrate u use one oxaloacetate..then u regenerate what you already used so can’t make glucose