5th Unit / Ch 19 Amino Acids: Disposal of Nitrogen Flashcards
Overall Nitrogen Metabolism 19 1.1
What are the three inputs to the amino acid pool shown?
Three inputs to the amino acid pool are the
(1) degradation of body protein,
(2) degradation of dietary protein, and
(3) synthesis of nonessential amino acids.
Overall Nitrogen Metabolism 19 1.2
What is “protein turnover”?
iT is the ongoing synthesis and degradation of a protein. In
a healthy adult, the rate of synthesis is just sufficient to replace the amount of protein that was degraded, resulting in a steady state . Turnover rate varies among proteins.
Overall Nitrogen Metabolism 19 1.3
Compare and contrast the proteasomal and lysosomal systems of protein degradation.
Proteasomal protein degradation involves the three-step, ATP-dependent enzymatic tagging of proteins with > 4 Ub followed by cleavage to small peptides in the cytosolic proteasome as Ub is recycled. The proteasomal system is
selective and is influenced by structural aspects of the protein.
In contrast, the relatively nonselective lysosomal system is ATP and Ub independent and uses
acid hydrolases to cleave proteins.
Overall Nitrogen Metabolism 19 1.4
What does it mean for an individual to be in N balance? Positive N balance?
N balance means that the amount of N going into the body equals the amount going out. In a state of positive N balance , however, more N is going in than is coming out, such as in periods of growth (including pregnancy) and in
recovery from muscle atrophy (e.g., as occurs with prolonged immobilization or disease).
Dietary Protein Digestion 19 2.1
What enzyme of protein digestion, denoted by the red question mark, is produced by the stomach?
Pepsin, an acid-stable endopeptidase, is secreted by gastric chief cells as the zymogen pepsinogen. [Note: In the presence of HCL from gastric parietal cells, pepsinogen undergoes
autocatalytic cleavage to pepsin.]
Dietary Protein Digestion 19 2.2
What role does enteropeptidase play in digestion?
Enteropeptidase, a serine protease of the brush border membrane of intestinal mucosal cells, cleaves trypsinogen to trypsin, a serine protease that converts all other pancreatic
zymogens to their active forms through cleavage at the carboxyl side of Arg and Lys residues in the proteins.
Dietary Protein Digestion 19 2.3
Why is celiac disease a pathology of malabsorption?
Celiac disease (gluten enteropathy) is a chronic disease of the gastrointestinal tract caused by an immune-mediated response to gluten (a protein in wheat, barley, and rye) that
atrophies the brush border, resulting in malabsorption .
Dietary Protein Digestion 19 2.4
What amino acids are expected to be present in the urine of an individual with cystinuria?
**Cystinuria** is an Amino Acid Reabsorbtion defect in the transporter that takes up cystine and the dibasic amino acids ornithine, Arg, and Lys (sometimes represented as **COAL**) in the proximal tubules, causing them to appear in the urine. Cystine can precipitate at the acidic pH of urine and _form stones_ in the urinary tract (**cystine urolithiasis**).
Nitrogen Removal 19 3.1
What is the general name of the enzymes that catalyze the reversible transfer of amino groups from one carbon skeleton to another, as shown? What vitamin is the
source of the coenzyme used in the reaction?
Aminotransferases (transaminases) catalyze the reversible transfer of amino groups from most amino acids to a-KG, a process known as transamination.
The products are an a-keto acid and Glu.
[Note: Lys and Thr are not substrates for aminotransferases .] The PLP coenzyme required by these enzymes is derived from vitamin B 6 (pyridoxine).
Nitrogen Removal 19 3.2
What is the primary fate of Glu during periods of amino acid catabolism?
During amino acid catabolism, Glu is oxidatively deaminated to a-KG + NH 3 by the mitochondrial enzyme Glutmine DeHydrogenase that uses NAD+ as a coenzyme as shown. ADP (a low-energy signal) is an allosteric
activator.
[Note: The GDH reaction is reversible and the reductive biosynthesis of Glu uses NADPH.]
Nitrogen Removal 19 3.3
Which set of clinical findings in blood is more suggestive of liver disease?
A. ↑AST, ↑ALT, ↑bilirubin
B. ↑AST, ↔ALT, ↔bilirubin
Choice A (↑ AST , ↑ ALT , ↑bilirubin) is more suggestive of **liver disease**. **AST** and **ALT** are intracellular enzymes that leak into the blood when liver cells are damaged. The rise in **bilirubin** indicates a problem with hepatic metabolism. **ALT** is found primarily in liver, whereas **AST** is also found in heart and skeletal muscle and RBCs. Therefore, a rise in AST with a normal value for ALT and bilirubin suggests damage to nonhepatic tissues.
Ammonia and the Urea Cycle 19 4.1
What is the amino acid product of the reaction shown? Would you expect the enzyme that catalyzes
the reaction to be a synthase or a synthetase ? What is the biologic significance of the reaction?
Gln is the amino acid product. Because the catalyzing enzyme requires ATP, it is a synthetase (glutamine synthetase). The reaction utilizes toxic NH3 (generated in amino acid catabolism) to form Gln, a nontoxic transporter of NH3 through the
blood. Gln, primarily generated by skeletal muscle, is taken up and metabolized by the liver, intestine, and kidneys.
Ammonia and the Urea Cycle 19 4.2
What is the function of the UC, and where does it occur? What is the regulated enzyme? What is the
fate of the urea product?
The UC converts toxic NH3 to nontoxic urea. This ATP-dependent process occurs in hepatocytes (the first two reactions in the mitochondrial matrix, the remaining three in the cytosol). [Note: Gluconeogenesis and heme synthesis also require enzymes of the matrix and the cytosol.] The regulated enzyme of the UC is
Carbamoyl phosphate synthetase I (CPS I),
which requires N-acetylglutamate (N-AcGlu) as an allosteric activator. Urea, the most important means of disposing of NH3, is transported through the blood to the kidneys for excretion. [Note: The UC uses and regenerates ornithine.]
Ammonia and the Urea Cycle 19 4.3
How do the liver and the kidneys metabolize Arg differently? How does this relate to Arg being nonessential?
The liver expresses the full complement of UC enzymes, including arginase-1 that hydrolyzes Arg to urea and ornithine, whereas
the kidney is able to make Arg
from citrulline but does not contain arginase-1.
[Note: Arg is used for renal NO synthesis.]
Ammonia and the Urea Cycle II 19 5.1
What are the sources of the N that appears in urea?
NH3, primarily from amino acid catabolism, provides one N of urea, and Asp provides the other. [Note: Glu is the immediate precursor of the NH3 (via GDH ) and of the Asp (via AST).]
Ammonia and the Urea Cycle II 19 5.2
What happens to the fumarate produced by argininosuccinate lyase?
The fumarate produced by cytosolic argininosuccinate
lyase is hydrated to malate, which can be transported into the
mitochondrial matrix, enter the TCA cycle, and be oxidized to OAA .
The OAA can be used in gluconeogenesis or transaminated to Asp
and used in the UC.
Ammonia Metabolism 19 6.1
How do the UC, glutaminase, and glutamine synthetase shown work together within hepatocytes to keep blood
NH 3 levels low?
Periportal hepatocytes are rich in glutaminase, which produces toxic NH3 (and Glu) from Gln (its nontoxic carrier), and in the enzymes of the UC that converts the NH 3 to nontoxic urea for transport to the kidneys. Any NH 3 missed by these reactions is “scavenged” by glutamine synthetase in the perivenous hepatocytes and used to convert Glu to Gln (glutamic acid)
that is sent out into the blood. Together, these processes prevent hyperammonemia , a condition that has a neurotoxic
effect.
