Basics of fatty acids and amino acids
What is the main storage molecule for fatty acids within the body? Where are these molecules stored?
Triacylglycerols, stored in adipose tissue (specialised fat storing cell).
What makes TAGs such excellent energy storage molecules?
Produces 8 Acetyl-CoA which leads to 106 ATP! Basically, you get huge amounts of energy from this one molecule.
What are the two major parts of an amino acid which undergo diverging catabolic pathways?
Carbon skeletons and amino groups
What group does S-adenosylmethionine (SAM) carry?
Methyl
What is the cause of Phenylketonuria (i.e., what enzyme is affected)?
Phenylalanine hydroxylase
How are proteins digested into amino acids?
Begins in stomach and completed in intestine:
Pepsin (stomach)
Trypsin, chymotrypsin, carboxypeptidase (pancreas)
Peptidases (converts to amino acids)
Once the TAG molecule is hydrolysed, what happens to glycerol?
It becomes an intermediate in glycolytic and gluconeogenic pathways – converted to pyruvate or to glucose respectively.
In what form is nitrogen removed from amino acids during catabolism?
Ammonia
What metabolic pathway can the degraded methionine enter, and as what molecule?
It is converted to succinyl-CoA, so can enter the citric acid cycle.
What builds up in the body in phenylketonuria, and what are the symptoms?
Phenylalanine; intellectual disability, seizures,
behavioral problems, and mental disorders (if untreated)
How are dietary lipids consumed through food, digested, and transported in the blood, to allow fatty acid catabolism to occur?
Dietary lipids are digested by pancreatic lipase and transported in chylomicrons in the blood.
How does beta oxidation differ between odd and even chain fatty acid molecules?
Odd-chain fatty acids yield propionyl CoA in the final thiolysis step: it’s a 3C molecule.
Carboxylation occurs analogous to pyruvate carboxylase, epimerisation, then cobalamin dependent isomerisation by methylmalonyl-CoA mutase to form Succinyl-CoA.
What is the first step in amino acid breakdown?
The removal of nitrogen by transaminases.
The alpha amino groups of the amino acids are turned into ammonia by transamination to form glutamate. This is followed by oxidative deamination (by glutamate dehydrogenase).
What is the cause of Alkaptonuria (i.e., what enzyme is affected)?
Homogentisate 1,2-dioxygenase
One of the byproducts of the urea cycle is fumarate. How does this molecule link into another method of energy production?
Fumarate can enter the citric acid cycle.
In states of fasting, starvation, or impaired blood glucose regulation, the catabolism of fatty acids (whether from dietary lipids or stored TAGs) leads to the formation of large quantities of ketone bodies. With reference to all metabolic pathways involved, why would this occur, and why could this be life threatening?
Ketone bodies formed from:
How do ketogenic amino acids differ in the breakdown of their carbon skeleton? Why might this be regarded as ketogenic?
Degraded to acetyl-CoA or acetoacetyl-CoA, can form ketone bodies (and citrate from acetyl-coa)
What builds up in the body with alkaptonuria, and what are the symptoms?
Homogentisate; black urine due to oxidation of homogentisate.
Generally speaking, how does the catabolism of aromatic amino acids differ to non-aromatic amino acids?
Oxygenases are required for degradation of aromatic amino acids (Phe, Tyr).
Describe the general process of the beta oxidation of a fatty acid chain, and how this leads to the generation of ATP.
Fatty acids undergo oxidative removal of successive two-carbon units in the form of acetyl-CoA.
Cleavage of 3-ketoacyl CoA by thiolase. Creating acetyl-CoA and shortened acyl-CoA.
Muscle fibres often have large rates of amino acid breakdown. How do they safely remove the nitrogen created as a byproduct of this, and how does it feed back into the muscle tissue?
Nitrogen transferred to alanine by ALT (alanine aminotransferase). Transported to liver and transformed into pyruvate. Forms glucose via gluconeogenesis, then transported back to muscle. This is the glucose-alanine cycle:)
Plot twist, a different condition!
With reference to the site the urea cycle takes place, what are some potential causes of (diseases that cause) severely elevated blood ammonia levels (hyperammonemia)?
Liver mitochondria – caused by diseases that result in either acute or chronic liver failure (hepatotoxins, acute failure e.g., hepatitis B; chronic failure e.g., hepatitis B or C).