Exam #3 Flashcards
What are the fates of amino acids?
- Protein Synthesis
- Synthesis of other nitrogenous compounds
Purines and pyrimidines (nucleotide components)
Catecholamines (adrenaline and noradrenalin)
Neurotransmitters (serotonin) - Biological fuel from the carbon skeleton
What are the two key reactions in amino acid metabolism?
Transamination & Oxidative Deamination
What is the coenzyme required for transamination to occur?
Pyridoxal phosphate (PLP)
What are the gluconeogenic substrates included in transamination?
Alanine = Pyruvate Aspartate = Oxaloacetate
What is transamination?
The transfer on 1 amino group from an amino acid to an alpha keto acid
What is oxidative deamination?
The removal of an amino group from glutamate to form alpha-ketoglutamate, ammonium, and NADPH. This reaction can be inhibited depending on presence of substrates.
What reactants form alpha-ketoglutamate and ammonium?
GDP and ADP
What are the substrates that activate formation of glutamate and water?
GTP and ATP
What are the two stages of nitrogen disposal?
- Removal of amino group from amino acid
2. Formation of urea via ornithine cycle
The 2 routes for amino group removal
- Transdeamination = Transamination + Oxidative Deamination
- NH4+ and CO2 enter the ornithine cycle and converted to carbamoyl phosphate.
- Transamination
- Step 1. Transfer of amino group to alpha-ketoglutamate forming glutamate
- Step 2. Transfer of amino group from glutamate to oxaloacetate forming aspartate. enters ornithine cycle and converted to argininosuccinate.
What are the reactants of the ornithine cycle?
Through transdeamination route, ammonium enters the urea cycle and is converted into carbamoyl phosphate.
What are the 2 rate limiting enzymes producing carbamoyl phosphate?
- 2 ATP —> 2 ADP
2. Carbamoyl Phosphate Synthetase I
What compound is produced from carbamoyl phosophate?
Citrulline
Second step of ornithine cycle
What is argininosuccinate produced by?
Aspartate which is generated by the condensation of citrulline.
An energetic step, costs 2 ATP equivalents
What two compounds are produced by the cleavage of argininosuccinate?
Fumarate and Arginine
What are the fates of fumarate?
- Can be oxidized to produce oxaloacetate which is transaminated to produce aspartate which can go back into the ornithine cycle.
- The NADH produced from this reaction can go back into the electron transport chain to produce 2.5 ATP
What does the cleavage of arginine produce?
Ornithine and urea
- Urea transported to kidney
What occurs to protein in the fed state?
- When there’s an abundance of amino acids in the liver, they can be used for protein synthesis or the synthesis of other nitrogenous compounds
- Amino acids released into the blood can be utilized for protein synthesis by other tissues or deaminated. The carbon skeletons converted to pyruvate, acetyl CoA, or TCA cycle intermediates.
What happens to protein during the fasted state?
The protein stored in the muscle can be released transaminating amino acids to alanine and glutamine.
- Glutamine is taken up by intestine and kidney for nucleotide synthesis and hydrolyzed to ammonium which enters ornithine cycle.
- Alanine is converted to pyruvate and then glucose via gluconeogenesis or transaminated to glutamate to be disposed.
What happens to protein during the fed state?
A large proportion of amino acids transaminated to alanine which is released to portal circulation to liver. Fates of alanine include
- Protein synthesis
- Transamination to glutamate, oxidative deamination to produce ammonia.
Describe ketogenesis
During high rates of fatty acid oxidation, large amounts of acetyl CoA are produced
What are the precursors of ketogenesis and what does it produce?
Precursors: 2 Acetyl CoA
Products: The 3 ketone bodies (Acetoacetate, Beta-hydroxybutyrate and acetone)
What are the sources of acetyl CoA for ketogenesis to occur?
- Glucose
- Fatty acids
- Amino acids
What are the fates of acetyl CoA?
- Oxidation in TCA cycle
- Ketone body synthesis
- Syntheis of long chain fatty acids
What occurs in lipid metabolism during fed state?
- Dietary fat is hydrolyzed to free fatty acids and glycerol in intestines by pancreatic lipase.
- Short chain fatty acids can enter circulation directly or incorporated into chylomicrons.
- Lipoprotein lipase releases triglycerides in chylomicrons. The fatty acids can be stored in adipose tissue, used for energy, or reesterified to triglycerides in liver and exported as VLDL.
How does insulin affect lipid metabolism?
- Insulin stimulates lipoprotin lipase or synthesis of fatty acid and triglyceride in the liver
- Inhibits hormone sensitive lipase
What occurs in lipid metabolism in the fasted state?
Hormone-sensitive lipase activated by glucagon (fasting) or epinephrine (exercise) hydrolyzes fat in adipose tissue to glycerol and fatty acids
- Fatty acids used as energy source in mitochondria
- Glycerol converted to glucose
What do glucagon and epinephrine do in lipid metabolism?
- They both stimulate hormone sensitive lipase
2. Inhibit lipoprotein lipase, fatty acid synthesis, and triglyceride synthesis.
What leads to lipidosis
- Increased delivery of fatty acids to liver
- Decreased hepatic fatty acid oxidation
- Decreased ability to secrete VLDL
What leads to lipidosis?
Obesity or stress
What occurs during idiopathic feline lipidosis?
- In starvation, the lack of availability of dietary glucose causes an increase in growth hormone and decrease in insulin
- leads to accelerated peripheral lipolysis and a massive accumulation in fatty acid release
- Fatty acids are taken up by the liver and converted to triglycerides
What causes idiopathic feline lipidosis?
- Arginine Deficiency -> Arginine is an intermediate for urea cycle. Leads to acculumation of urea in system and more fatty acids liberated in liver to balance energy demands
- Carnitine Deficiency -> Carnitine is found in beta-oxidation and aids in transporting fatty acids into mitochondria to be oxidized. When deficient, fatty acids can’t be oxidized and circulating fatty acids are transported back to liver.
Compare & Contrast water & fat soluble vitamins
- Water soluble vitamins function as a coenzyme. Typically have to be supplied daily.
- Fat soluble vitamins can be stored in adipose tissue. Toxicity can be a potential problem
What are the 4 coenzymes required by pyruvate dehydrogenase complex and their vitamin precursors
- –> Acetyl CoA
- > Coenzyme A required for its production. Is produced by pantothenic acid - –> NAD+
- >Niacin (vitamin B3) constitutes to it’s formation - –> FAD+
- > Riboflavin is important in the formation of FAD+ - –> Lipoic acid
- –> TPP
- > TPP is the active form of Thiamin (vitamin B1)
What are the functions of vitamin C?
- Collagen synthesis
- Animo acid metabolism
- Antioxidant activity
What are the functions of thamin?
- Transketolase —> NADPH
- Pyruvate Dehydrogenase Complex: Converts Pyruvate —> Acetyl CoA
- alpha-Ketoglutarate dehydrogenase producing succinyl CoA for TCA cycle
- Branch chain alpha-keto acid dehydrogenase for branch chain AA metabolism
- Phytonic acid metabolism
Functions of vitamin D
- Increases calcium absorption in the gut by upregulating production of calbindin (a calcium binding protein of enterocytes)
- Hydrolyzed vitamin D (from liver & kidney) forms Calcitrol which increases alkaline phosphatase absorption of phosphorus in the gut
- –> There is increased calcium and phosphorus release from the bone.
Why is transamination important?`
- Non-essential amino acids are produced from essential amino acids
- Efficiently convert alanine to form aspartate (which enters urea cycle).
How absorption of di-, tri-, and tetra- peptides occurs?
Occurs via PEPT1 (proton coupled) transporters. This transports di- and tri- peptides in the proximal end of small intestine. Di- and tri- peptides are absorbed for efficiency. It’s faster and easier to absorb 2-3 amino acids at a time than 1 (less competition for transporters)
