Lecture 10 - Amino Acid Metabolism

Question 1

Where do free amino acids come from? (3)

What are they used for? (3)

Are free amino acids numerous in the body?

Answer 1

Sources:

1. Degradation of ingested protein
2. Biosynthesis of amino acids
3. Degradation of endogenous protein

Uses:

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

Free amino acids are in LOW CONCENTRATIONS in the body. (<1mM)

Question 2

What are nutritionally non-essential amino acids?

Amino acids that must be supplied in the diet are referred to as_______

Answer 2

Amino acids that can be synthesized in the body from precursor molecules.

2. Nutritionally essential

Question 3

What are the two primary pathways for protein degradation?

Answer 3

1. ATP dependent ubiquitin proteasome system

2. Lysosomal pathway

Question 4

The half-lives of proteins ranges from few minutes to many days. Which proteins usually have the fastest turnover rates?

Answer 4

Regulatory proteins –> RATE LIMITING ENZYMES

Question 5

Adults synthesize and degrade _____ of their total body protein every day.

True or false: There is NO NET ACCUMULATION of protein even on a high protein diet.

Answer 5

2-3% (about 300g)

TRUE! No net accumulation !

Question 6

Does amino acid catabolism occur if there is no protein being supplied in the diet?

Answer 6

YES!!!
-always being catabolized

Body loses about 55g of protein every day
- this loss must be replaced by dietary protein!

Question 7

A daily protein intake less than ____ per day will result in loss of body protein.

What happens to excess amino acids?

Answer 7

55g

If intake is GREATER than 55g, the excess amino acids are DEGRADED

Question 8

What happens to the following in amino acid catabolism:

1. Nitrogen of the amino group
2. Carbon skeletons

Answer 8

1. Nitrogen of the amino group
   - incorporated into urea and excreted
2. Carbon skeletons
   - converted for ENERGY immediately or stored as GLYCOGEN or FAT for future energy production

Question 9

In regards to nitrogen balance, a normal adult is typically in _____.

How?

Answer 9

Nitrogen Equilibrium

• rate of protein synthesis equals rate of protein degradation
• the amount of nitrogen taken in as dietary protein, is balanced by excretion of nitrogen as urea

Question 10

What are the two values that define nitrogen balance?

Answer 10

Nitrogen Ingested - Nitrogen excreted (as urea)

Question 11

When is the body in positive nitrogen balance (state examples)

Negative nitrogen balance?

Answer 11

1. Positive :
   - growth in children
   - pregnancy
   - bodybuilding

Synthesis> degradation (nitrogen accumulates)

2. Negative:
   - starvation
   - protein malnutrition
   - trauma
   - cancer
   - burn injury
   - sepsis
   - surgery
   Nitrogen ingested< than excreted

** MUSCLE MASS WILL DECREASE**

Question 12

Where does urea biosynthesis occur?

What organ is responsible for excreted it?

Answer 12

1. LIVER

2. Kidney

Question 13

What is the path of NH2- from amino acids to urea?

Answer 13

NH2- from amino acids –> glutamate –> ammonia/aspartate

–> UREA

Question 14

What is the first step in the degradation of amino acids?

What occurs?

Answer 14

Transamination

• transfer of an amino group to alpha-ketoglutarate to form GLUTAMATE (from ALANINE)

Question 15

What is the amino group acceptor in all amino acid transaminase reactions?

Amino groups are collected to form what product?

Answer 15

ALPHA KETOGLUTARATE

GLUTAMATE

Question 16

What cofactor is required for transaminases?

Answer 16

Pyridoxal Phosphate

Question 17

What transaminase are important in clinical diagnosis? (usually low in serum)

When do they usually appear?

Answer 17

1. ALT (Alanine Transaminase)
   - hepatitis, cirrhosis, liver metastases, obstructive jaundice, infectious mononucleosis, pancreatitis, renal disease, alcohol ingestion
2. Aspartate Transaminase (AST)
   - liver disease, myocarditis, pericarditis, myositis, muscular dystrophy, trauma, pancreatitis, renal infarct, eclampsia, neoplasia, cerebral damage, seizes, hemolysis, alcohol ingestion

• appear during tissue damage (hepatitis) –> hepatocyte damage releases this cytosolic enzymes

Question 18

____ and _____ provide the nitrogen atoms that are used to make urea.

What are both of these structures formed from?

Answer 18

1. Aspartate
2. Ammonia

• formed from GLUTAMATE

Question 19

Synthesis of Urea from Ammonia and Aspartate:

1. What is the major regulated step?
   - what enzyme catalyzes this?
2. What are the next compounds that are formed? (4)

• when is fumarate released?
• what happens after urea is released? (which enzyme is needed)

Answer 19

1. Formation of carbamoyl phosphate!!!
   - formed from N-acetylglutamate!!!

2.

• Citrulline
• Arginosuccinate
• formation of arginine(releases fumarate)
• formation of urea (enzyme ARGINASE)
• ornithine is regenerated

Question 20

Where does the synthesis of Carbamoyl Phosphate and Citrulline take place? (urea cycle)

What 2 components of the Urea Cycle enter and leave (2 total)?

Answer 20

1. MITOCHONDRIA
   - other reactions are in the cytosol
2. citrulline leaves
   Ornithine ENTERS
   the mitochondria respectively via an exchange transporter

Question 21

What substance activates the enzyme that makes Carbamoyl Phosphate? (carbamoyl phosphate synthase I)

What leads to increased levels of this substance?

This stimulates the production of _______

Answer 21

1. N- Acetylglutamate
2. GLUTAMATE
3. UREA
   - long term exposure to a high protein diet or to a high rate of protein degradation leads to increased levels of urea cycle enzymes

Question 22

Although urea synthesis occurs in the liver, amino acid metabolism occurs in other tissue than the liver (muscle).

How is nitrogen transferred to the liver for conversion to urea? (2 main carriers of nitrogen to the liver)

Why these 2?

Answer 22

1. Alanine-Glucose cycle
2. Glutamine

• present in blood at high concentrations

Question 23

BUN is useful for what?

Answer 23

Plasma urea concentration

• elevated in renal disease, dehydration, GI bleeding, leukemia, Heart failure, shock, Urinary tract obstruction, acute MI

**decreased in**
liver failure
over hydration
pregnancy 
acromegaly

Question 24

Where in TCA can amino acids enter?

Answer 24

1. Pyruvate
2. Acetyl CO A
3. OAA
4. Fumarate
5. Succinyl Co A
6. Alpha-ketoglutarate

Question 25

What fraction of amino acids are stored following a meal?

What stimulates transient storage in muscle?

What happens to these levels after an overnight fast?

Answer 25

1/3 are stored as protein

2/3 are degraded immediately

2. Protein synthesis stimulation by amino acids and insulin
   - and inhibition of protein degradation
3. Overnight fast: insulin decreases and plasma amino acids decrease
   = PROTEIN DEGRADATION and release of amino acids for use by the liver for gluconeogenesis

Question 26

What is the main function of urea biosynthesis?

What is the affect of hyper ammonia?

Answer 26

AMMONIA DETOXIFICATION

2. COMA
   ex: hepatic coma from decreased capacity of liver to remove ammonia via urea production

Question 27

Define what causes:

1. Acquired Hyperammonia

2. Genetic Hyperammonia

Answer 27

1. Acquired Hyperammonia
   - portal-systemic shunting
   = diversion of blood around the liver in response to cirrhosis
   - ammonia produced by bacteria in colon is absorbed but not converted to urea
   = “portal-systemic encephalopathy”
2. Genetic Hyperammonia
   - Deficiency of a real cycle enzyme

Question 28

What is the fate of carbon skeletons?

What classifies them as glycogenic or ketogenic?

Answer 28

To be used for energy

Glucogenic:
yield TCA cycle intermediates or pyruvate for gluconeogenesis

Ketogenic:
yields acetyl CO a, Acetoacetyl Co A, acetoacetate

Question 29

What amino acids are both ketogenic and glycogenic?

Answer 29

1. Phenylalanine
2. Tyrosine
3. Tryptophan
4. Threonine
5. Isoleucine