AA Metabolism and Urea cycle Flashcards
What is the urea cycle and where does it occur? Where is it excreted?
It is the detoxification of the NH3 that results from the aa oxidation. It occurs ONLY IN THE LIVER. Gets excreted via the kidneys.
What are the possible pathways for aas?
1- Oxidation to form energy and release CO2
2- Excess form: ketone bodies, glucose
3- Form proteins
What are sources of NH3?
1- Oxidation of the alpha-amino grp in aas
2- AMP deaminase activity in purine metabolism. Pyrimidine metabolism as well.
3- MAO (monoamine oxidase) that oxidizes biogenic amines such as histamine and neurotransmitters (dopamine,…)
What are the intermediates aas can be changed to?
After removal of the alpha amino group, we will have an alpha keto acid that can be transformed into: 1- Acetoacetate and Acetyl CoA 2- α-keto glutarate 3- OXAC 4- Fumarate 5- Succinyl CoA 6- Pyruvate 7- Proprionate
Differentiate between ketogenic and glucogenic aas.
1- Ketogenic aas are those that can be catabolized into acetoacetate. (2 –> leucine and lysine)
2- Glucogenic aas can eventually form glucose, hence they may give rise to intermediates of the TCA cycle, or propionate.
3- Other aas are both Glucogenic and Ketogenic:
• Trp yields acetoacetate and pyruvate.
• Ile yields acetyl CoA, and propionyl CoA that is converted to succinyl CoA.
(4 –> isoleucine, tryptophan, tyrosine, and phenylalanine)
What are low quality proteins? Give 2 examples.
no high nutritional value due to the lack of EAAs such as corn (tryptophan and lysine inadequacy) and beans (low in methionine).
What does the improper intake of EAA result in ?
Protein Energy Malnutrition (PEM):
1- Kwashiorkor: Inadequate protein intake, while the caloric intake is normal. => The diet is inadequate in terms of protein quality.
- Patients will have a lower concentration of serum protein (albumin), and an imbalance in CHY and lipid metabolism.
- ammonia excretion will be high because the endogenous proteins are being catabolized.
2- Marasmus: It mimics starvation because both protein and caloric intake are inadequate. => Depletion of TGs, Glycogen, proteins + No food source.
- Allowing food intake after a period of time will have no effect because they lose their ability to absorb and digest the nutrients (enzymes become non-functional).
- In general, in both diseases, the immune system is compromised. There is inadequate growth, with deleterious brain and mental effects.
Nitrogen Balance
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What causes a deficiency in pancreatic secretions?
Individuals with deficiency in pancreatic secretion (Chronic pancreatitis: inflammation of the pancreas, Surgical removal of the pancreas), or with bile duct obstruction have incomplete lipid or protein digestion. The undigested proteins or lipids will be present in feces giving it a whitish clay pale color. This is known as Steatorrhea.
How are aas absorbed at the level of the intestine?
1- AAs are transported via the epithelial cell brush borders of the mucosa and serosa via Na+/aa cotransporters driven by the concentration gradient of NA+ that is maintained because of the Na+/K+ ATPase pumps present on the serosal membrane.
2- If concentration of aas is high intracellularly, aas get transported to the blood by facilitated diffusion
3- Starvation causes take up of aas from blood by intestinal epithelial cells.
4- Gamma Glutamyl pathway
Are there different types of cotransporters? Why?
Yes, different cotransporters are specific for different aas (neutral, basic, etc…). Some cotransporters overlap in specificities and aas get transported by a multiple.
Define the Gamma Glutamyl pathway.
o γ – Glutamyl Cycle is another mechanism to transport aas. It occurs in the kidney tubules, intestines, RBCs and in cells where GSH/GSSG ratio should be HIGH.
- It absorbs aas as dipeptides.
Glutamyl cycle.
notes
Name the disorder related to Gamma Glutamyl cycle.
Oxoprolinuria caused by a deficiency in GSH synthase, leading to hemolytic anemia:
- Due to GSH Synthase deficiency, γ – Glutamyl Cysteine accumulates, but it resembles the 1st dipeptide formed in the cycle, where the introduced aa is Cys. => γ – Glutamyl Cysteine undergoes cyclization, releasing Cys and Oxo-proline. Oxo-proline accumulates in the cell, and is then excreted in urine. + GSH (reducing agent) ↓, which causes hemolysis of RBCs.
