L19- Disorders of Energy Metab 2 (#2) Flashcards
Case 4: A 2-year-old male conventional short hair cat is brought to the veterinary clinic with severe signs of hyperammonemia. He manifests severe vomiting,
excessive flow of saliva, hyperactivity, spasms, tactile hyperesthesia and ataxia. His limbs are extended, with exposed claws. His owner reports that he has been growing healthy for his entire life until one hour ago. He explained that his cat fasted overnight, but signs started soon after he
accidentally consumed a casein-based, arginine-deficient diet. A blood test revealed an unusually elevated level of
orotic acid and glucose in circulation. A case of ____ deficiency is suspected.
Arginine Deficiency
Study q: In what metabolic pathway was arginine produced? (Arg def)
In the urea cycle
Study q: Why does the lack of Arg lead to symptoms of hyperammonemia?
- Urea cycle is the metab-pathway used by mammls to eliminate ammonia from the body
Without ____, the urea cycle cannot convert ammonia into urea and hyperammonemia occurs (Arg deficiency)
Arginine
After cat east a meal, highly active protein catabolic enzymes will break down proteins into AA, and AAs into a c-skeleton (a-keto acid) and a large amount of ____ which needs to be _____ in the urea cycle
Ammonia which needs to be DETOXIFIED in the urea cycle
What can’t cats do compared to other species when it comes to “keeping up” with the increased ammonia?
Ornithine and citruline synthesis occurs in animals other than cats
Study q: Hyperglycemia was observed at time of admission- why did hyperglycemia happen? (hint: epinephrine (stress h) inhibits insulin secretion) (4)* Long explaination
- Metabolic stress results in Epi secretion
- Epi inhibits insulin secretion and activates glucagon secretion which creates a low insulin/high glucagon
- Results in activation of gluconeogenesis and inhib of blood glucose intake via GLUT-4
- Thefore blood glu lvls will increase do to increase release and lower uptake
Study q: In addtion to hyperglycemia, orotic aciduria (high lvls orotic acid in the urine) is observed- how can that be eplained? (hint: intermed of purimidine biosynthesis pathway) (2)* Long explanation
Arg deficiency leads to carbamoyl-phosphate (mito) accum, which leaks out of mitochondria into cytoplasm and leads to carbamoyl-phosphate (cyto) accumulation
- Carbamoyl-phosphate (cyto) enters the pyridmidine biosynthesis pathway, bypassing the regulatory step and leading to increase prod of all molecules downstream –> inc orotic acid –> spills to urine
A combination of 3 mchanism are suggested to explain ammnia toxicity- what are they?
- Decreased level of a-ketoglutarate which SLOWS down TCA cycle and energy prod in brain cells decrease
- Increased level of glutamate which IMBALANCES in amount of neurotransmitters in the brain
- Increased level of glutamine which leads to INCREASED RISK of cerebral edema
Hyperammonemia in other species: When does urea poisoning in cattle occurs which intake of dietary ___ produces so much ___ that exceeds ability of ___ to detoxify it
Dietary urea
Ammonia
Need liver to detoxify it
Hyperammonemia in other species study q: If possible, affected animals should be treated by ruminal infusion of 5% acetic vinegar, which creates a more acidic pH. What is the rationale of this Tx to minimize hyperammonemia?
- Acetic acid lowers rumen pH and prevents further absorption of NH3 by converting NH3 to NH4+ (charged, cannot be absorbed).
- Also, it forms ammonium which can be used by rumen microflora but does not release NH3
Hyperammonemia in other species: Citrullinemia in cattle is the result of a mutation in the argininosuccinate synthetase gene, leading to a _____________ of the urea cycle- what does it result in and what is the Tx plan like?*
Leading to a dystfunction of the urea cycle
- Results in hyperammonemia and associated neurological symptoms
- TX usually unsucessfaul- euthanized
Hyperammonemia in other species: Ammonia toxicity in horses can be the result of consuming toxic plants that contain hepatotoxic alkaloids which causes ____________ because
Liver dysfuncion, bc the liver cannot convert ammonia to urea, leading to hyperammonemia
Hyperammonemia in other species: Transient hyperammonemia can be the result of infection of a urease-producing bacteria within the intestine- why?
Urease breaks down urea into CO2 and ammonia, so increased amount of bacteria producing this enzyme would lead to increased amount of ammonia
Case 5: A six-year-old male budgerigar (common pet parakeet), was presented at the veterinary clinic for disturbance in his movement of several days’ duration. He seemed in pain and had trouble walking, flying and moving
the body about. Loss of feathers at the point of the elbow was noticeable. Multiple, firm, raised nodules (tophi) were noted at several periarticular locations, and a diagnosis of ___ was made. The severe articular gout was considered irresolvable, and the bird was euthanatized.
Gout
What are the 3 mechanisms found in nature to excrete ammonia? (gout)
- Ammontelism- urinary elim of nitrogen mainly in form of AMMONIA
- Urotelism- urinary elim of nitrogen mainly in form of UREA
- Uricotelism- urinary elim of nitrogen mainly in form of URIC ACID
What animals deal with ammonia? (Gout nature question)
Most aquatic animals, including fishes
What animals deal with urea? (Gout nature question)
Mammals, amphibians, sharks, and some bony fishes
