Steroid Metabolism and Protein/Amino acid degradation

Question 1

What is the precursor for all steroids?

Answer 1

Cholesterol, synthesised by acetyl-CoA

Question 2

What are the properties of bile acids?

Answer 2

Amphipathic

Question 3

What are bile acids used for?

Answer 3

applied to emulsify/ solubilise fats (emulsification)

• improves lipase efficiency (breakdown of fats)
• improves absorption in the intestines

Question 4

Why do you conjugate bile acids?

Answer 4

• conjugate with glycine or taurine

- conjugation lowers pKa values, leaving them as deprotonated salts and so is able to dissolve in water

Question 5

What are the 2 primary bile acids?

Answer 5

Cholic acid (3 OH groups) and chenodeoxycholic acid (2 OH groups)

Question 6

What are the 4 conjugated primary bile acids?

Answer 6

glycocholic acid, taurocholic acid, glycochenodeoxycholic acid and taurochenodeoxycholic acid

Question 7

How do you form secondary bile acids?

Answer 7

Anaerobic bacteria in the gut cleave amino acids and undergoes dehydroxylation

Question 8

What are the 2 secondary bile acids?

Answer 8

deoxycholic acid and lithocholic acid (each can be conjugated, just add glyco/tauro infront)

Question 9

What are steroid hormones?

Answer 9

signalling molecules that can have high specificity for binding with specific receptor molecules

Question 10

Where are steroid hormones synthesises?

Answer 10

adrenal cortex, testis and ovary

Question 11

What are the 5 groups that steroid hormones are classified into?

Answer 11

1. glucocorticoids
   - metabolism and immunology
2. mineralocorticoids - salt and water balance
3. androgens - male characteristic development and maintenance
4. Oeastrogens - female sexual development
5. Progestogens - pregnancy

Question 12

How many different steroid hormones can be formed from the metabolite progesterone?

Answer 12

testosterone, estradiol (oestrogen), cortisol and aldosterone

Question 13

What does the enzyme 5-alpha-reductase do?

Answer 13

Reduces testosterone to dihydrotetestosterone

Question 14

What are anabolic steroids?

Answer 14

a synthetic steroid hormone which resembles testosterone in promoting the growth of muscle
- stanozolol (doping in sports)

Question 15

What are anabolic steroids used for?

Answer 15

prescribed for health benefits

• growth stimulation to treat kids with growth failure
• induction of male puberty
• hormone replacement for men with low levels of testosterone
• promotes appetite

Question 16

What are the inputs into the free amino acid pool?

Answer 16

• dietary protein degradation

- body protein degradation

Question 17

What is the free amino acid pool used for?

Answer 17

• body protein synthesis
• ketogenic acids to form acetyl CoA
• glucogenic acids to form glucose/glycogen
• nitrogen elimination via urea cycle
• metaboliste synthesis

Question 18

How does dietary protein degradation occur via proteases? In stomach and pancreas.

Answer 18

1. in the stomach, pH 2 denatures proteins into random coils
2. pepsinogen is released from stomach as an inactive zymogen
3. pepsinogen uncoils at low pH and cleaves a 44 a.a. chain to produce pepsin via an autocatalytic mechanism
   - undergoes non-specific degradation
4. in intestinal lumen, pancreas secretes different proteases (high specificity) that produce free amino acids for absorption

Question 19

How does body protein degradation occur?

Answer 19

1. Tag protein with Ubiquitin tags
   - easy to define which proteins are ready for degradation
2. Proteasomes digest ubiquitin-tagged proteins

Question 20

How does the proteasomes enzyme work?

Answer 20

• 26S proteasome is constructed of 2 19S caps and a central 20S core
• 19S units bind to ubiquitin, then cleave ubiquitin to release
• directs protein in to catalytic core for degradation
• 20S core contains proteolytic active sites which degrades proteins in to 3-7 a.a. peptides
• peptides are released and further degraded by cellular proteases

Question 21

What is the difference between glucogenic and ketogenic amino acids?

Answer 21

Glucogenic a.a. can go off and be used to assist with glucose synthesis.
Ketogenic a.a. can break down acetyl CoA to form ketone bodies

Question 22

What is transamination?

Answer 22

• transfer of an amino group to an alpha-keto acid via transaminase-mediate reactions (a chemical reaction that transfers an amino group to a ketoacid to form new amino acids)

Question 23

Name example of an important transamination?

Answer 23

conversion of alpha-ketoglutarate to glutamate

- then glutamate reacts with other keto acids to form other amino acids

Question 24

How does transamination occur?

Answer 24

• uses pyridoxal phosphate (vitamin B6) as a cofactor

- forms pyridoxamine phosphate as an intermediate between amino acid and alpha keto acid

Question 25

What is oxidative deamination?

Answer 25

form of deamination that generates α-keto acids and other oxidized products from amine-containing compounds, and occurs largely in the liver and kidney

• amino acid degradation
• how to release nitrogen

Question 26

What allosterically regulates oxidative deamination?

Answer 26

positive regulation by high concs of ADP and GDP

negative regulation by high concs of GTP, ATP, leucine and coenzyme

Question 27

Give an example of oxidative deamination.

Answer 27

Glutamate to alpha-ketoglutarate (the latter can go into TCA cycle)
- 2 step process with one enzyme (glutamate DH)