Steroid Metabolism and Protein/Amino acid degradation Flashcards
What is the precursor for all steroids?
Cholesterol, synthesised by acetyl-CoA
What are the properties of bile acids?
Amphipathic
What are bile acids used for?
applied to emulsify/ solubilise fats (emulsification)
- improves lipase efficiency (breakdown of fats)
- improves absorption in the intestines
Why do you conjugate bile acids?
- conjugate with glycine or taurine
- conjugation lowers pKa values, leaving them as deprotonated salts and so is able to dissolve in water
What are the 2 primary bile acids?
Cholic acid (3 OH groups) and chenodeoxycholic acid (2 OH groups)
What are the 4 conjugated primary bile acids?
glycocholic acid, taurocholic acid, glycochenodeoxycholic acid and taurochenodeoxycholic acid
How do you form secondary bile acids?
Anaerobic bacteria in the gut cleave amino acids and undergoes dehydroxylation
What are the 2 secondary bile acids?
deoxycholic acid and lithocholic acid (each can be conjugated, just add glyco/tauro infront)
What are steroid hormones?
signalling molecules that can have high specificity for binding with specific receptor molecules
Where are steroid hormones synthesises?
adrenal cortex, testis and ovary
What are the 5 groups that steroid hormones are classified into?
- glucocorticoids
- metabolism and immunology - mineralocorticoids - salt and water balance
- androgens - male characteristic development and maintenance
- Oeastrogens - female sexual development
- Progestogens - pregnancy
How many different steroid hormones can be formed from the metabolite progesterone?
testosterone, estradiol (oestrogen), cortisol and aldosterone
What does the enzyme 5-alpha-reductase do?
Reduces testosterone to dihydrotetestosterone
What are anabolic steroids?
a synthetic steroid hormone which resembles testosterone in promoting the growth of muscle
- stanozolol (doping in sports)
What are anabolic steroids used for?
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
What are the inputs into the free amino acid pool?
- dietary protein degradation
- body protein degradation
What is the free amino acid pool used for?
- body protein synthesis
- ketogenic acids to form acetyl CoA
- glucogenic acids to form glucose/glycogen
- nitrogen elimination via urea cycle
- metaboliste synthesis
How does dietary protein degradation occur via proteases? In stomach and pancreas.
- in the stomach, pH 2 denatures proteins into random coils
- pepsinogen is released from stomach as an inactive zymogen
- pepsinogen uncoils at low pH and cleaves a 44 a.a. chain to produce pepsin via an autocatalytic mechanism
- undergoes non-specific degradation - in intestinal lumen, pancreas secretes different proteases (high specificity) that produce free amino acids for absorption
How does body protein degradation occur?
- Tag protein with Ubiquitin tags
- easy to define which proteins are ready for degradation - Proteasomes digest ubiquitin-tagged proteins
How does the proteasomes enzyme work?
- 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
What is the difference between glucogenic and ketogenic amino acids?
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
What is transamination?
- 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)
Name example of an important transamination?
conversion of alpha-ketoglutarate to glutamate
- then glutamate reacts with other keto acids to form other amino acids
How does transamination occur?
- uses pyridoxal phosphate (vitamin B6) as a cofactor
- forms pyridoxamine phosphate as an intermediate between amino acid and alpha keto acid
What is oxidative deamination?
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
What allosterically regulates oxidative deamination?
positive regulation by high concs of ADP and GDP
negative regulation by high concs of GTP, ATP, leucine and coenzyme
Give an example of oxidative deamination.
Glutamate to alpha-ketoglutarate (the latter can go into TCA cycle)
- 2 step process with one enzyme (glutamate DH)
