Amino Acids Flashcards
What are proteolytic enzymes?
Also called proteases break down dietary proteins
into their constituent amino acids in the stomach and the intestine
What is a zymogen?
The inactive form of an enzyme.
What enzyme begins the breakdown of proteins in the stomach?
Pepsin hydrolyzes proteins into smaller polypeptides.
What enzymes are produced by the pancreas to breakdown polypeptides in the duodenum?
Trypsin, chymotrypsin, elastase, and carboxypeptidase cleave polypeptides into oligopeptides and amino acids.
Where does further breakdown of oligopeptides occur?
At the brush border enzymes called amino peptidases breakdown oligopeptides into amino acids.
Where are amino acids absorbed?
Amino acids are absorbed through intestinal epithelial cells where they enter into the bloodstream.
How are amino acids absorbed?
Overlapping transport systems exist for amino acids in
cells including: facilitative transporters and
sodium-linked transporters, which allow the active transport of amino acids
into cells.
Other than food metabolism, where are proteins degraded for amino acid recycling?
This occurs within the cell continually. The amino acids released from proteins during turnover can then be used for
the synthesis of new proteins or for energy generation.
What do lysosomal proteases do?
Cathepsins degrade proteins that enter lysosomes.
How are cytoplasmic proteins recycled?
Cytoplasmic
proteins targeted for turnover are covalently linked to the small protein
ubiquitin, which then interacts with a large protein complex, the proteasome,
to degrade the protein in an adenosine triphosphate (ATP)-dependent process.
What does stomach acid do to ingested proteins?
HCl denatures and partially unfolds dietary proteins which allows better access to the protein structure for enzymes to act upon.
Where does pepsin cleave protein bonds?
Although pepsin has fairly broad specificity, it tends to cleave peptide bonds
in which the carboxyl group is provided by an aromatic or acidic amino acid
What does amylase break down?
Starches
What do lipase and colipase breakdown?
Dietary triacylglycerols
Why does the pancreas secrete bicarbonate into the duodenum?
In addition to neutralizing stomach acid it
raises the pH so that the pancreatic proteases, which are also present in pancreatic
secretions, can be active.
How are pancreatic enzymes activated?
Cleavage of trypsinogen to trypsin by enteropeptidase, then cleaves the other pancreatic zymogens, producing their
active forms
What do digestive enzymes actually “digest”?
The digestive
enzymes digest themselves, dietary protein, and intestinal
cells that are regularly sloughed off into the lumen.
Approximately how much dietary protein can the body absorb a day?
50-100g
How does the cotransport of Na+ and amino acids work in the small intestine?
The
cotransport of Na+ and the amino acid from the outside of the apical membrane to the
inside of the cell is driven by the low intracellular Na+ concentration.
How is low intracellular Na+ concentration maintained within the small intestine epithelium?
Low Na+ concentration results from the pumping of Na+ out of the cell by a Na+,K+-ATPase on the serosal membrane.
How are amino acids transported out of the cell?
Amino acids are transported out of the cell into the interstitial fluid, by facilitated transporters in the serosal membrane. At least six different Na+-dependent amino acid carriers are located in the apical brush border membrane of the epithelial cells. These carriers have overlapping
specificity for different amino acids.
What happens to the intestines during starvation? Why is this clinically relevant?
During starvation, the intestinal epithelia, like these other cells, take up amino acids from the blood to use as an energy source. Thus, amino acid transport across the serosal membrane is bidirectional.
What is an endopeptidase?
They hydrolyze peptide bonds
within chains.
What is an exopeptidase?
Enzymes that hydrolyze peptide bonds at the ends of an amino acid chain. There are two types.
What are the two types of exopeptidase?
Aminopeptidases remove the amino acid at the N-terminus and the carboxypeptidases remove the amino acid at the C-terminus of the protein.
What are the pancreatic endopeptidases?
Pepsin, trypsin, chymotrypsin, and elastase.
What are the pancreatic exopeptidases?
Aminopeptidases and carboxypeptidases
What are the intestinal aminopeptidases?
Dipeptidases, which are brush border enzymes.
What is hartnup disease?
Hartnup disease is an autosomal recessive disorder caused by a defect in the transport of neutral amino acids across both intestinal and renal epithelial cells. The signs and
symptoms are caused, in part, by a deficiency of essential amino acids. Hartnup disease involves defects in two different transport proteins. The defect is present both in intestinal cells, causing malabsorption of the amino acids from the digestive products in the intestinal lumen, and in kidney tubular cells, causing a decreased resorption of these amino acids
from the glomerular filtrate and an increased concentration of the amino acids in the urine.
What is Cystinuria?
Cystinuria is an inherited autosomal recessive disease that is characterized by high concentrations of the amino acid cystine in the urine, leading to the formation of cystine stones in the kidneys, ureter, and bladder.
How is the amino acid pool generated?
The amino acid pool within cells is generated both from dietary amino acids and from the degradation of existing proteins within the cell.
What does protein half life mean?
The time at which 50% of the protein that was synthesized at a
particular time will have been degraded.
What is the protein half life range?
Half life ranges from a few minutes to several days.
Intracellular degradation of unnecessary of damaged proteins involves what two mechanisms?
Cell mechanisms for degradation of proteins includes lysosomes and the ubiquitin/proteasome system.
What is the basic action of lysosomal protein turnover?
Within the lysosomes, the cathepsin family of proteases degrades the ingested proteins to individual amino acids. The recycled amino acids can then leave the lysosome and rejoin the intracellular amino
acid pool.
What is considered a “trigger” of lysosomal autophagy in regards to amino acid degradation?
Starvation is thought to be a trigger in this degradation process
What is ubiquitin?
Ubiquitin is a small protein (76 amino acids) that is highly conserved. It targets
intracellular proteins for degradation by covalently binding to the epsilon-amino group of lysine residues.
How does ubiquitin target proteins for degradation?
This is accomplished by a three-enzyme system that adds ubiquitin to proteins targeted for degradation.
What does polyubiquitinylated mean?
A process in which additional ubiquitin molecules are added to previous ubiquitin molecules, forming a long ubiquitin tail on the target protein.
What is a proteasome?
A protease complex that degrades the targeted protein, releasing intact ubiquitin that can again mark other proteins for degradation
Does ubiquination require energy?
Yes, ATP is used to “tag” the proteins with ubiquitin for degradation
What areas of a protein are proteasomes attracted to?
Regions rich in the amino acids proline (P), glutamate
(E), serine (S), and threonine (T) have short half-lives. These regions are known as
PEST sequences that are hydrolyzed by the ubiquitin–
proteasome system.
What are “nonessential” amino acids?
Amino acids that can be synthesized by the body and are not required by dietary intake through food.
What is endogenous protein turnover?
Protein recycling that happens within the body’s cells. Both degradation and synthesis of proteins within the body.
What is transamination?
The amino group
from one amino acid is transferred to another. And is the major process for removing nitrogen from amino acids.
What transamination reactions are readily reversible?
The reactions, which are readily
reversible, use pyridoxal phosphate (PLP) as a
cofactor.
What two amino acids cannot undergo transamination?
Lysine and Threonine
What are the enzymes called that catalyze the transamination process?
The enzymes that catalyze these reactions are known as
transaminases or aminotransferases.
What cofactor is required for transamination?
Pyridoxal phosphate
is the required cofactor for these reactions. Pyridoxal phosphate is derived
from vitamin B6 (pyridoxine).
Is the process of transamination reversible?
YES. Because these reactions are readily
reversible, they can be used to remove nitrogen from amino acids or to transfer
nitrogen to alpha-keto acids to form amino acids. Thus, they are involved both in amino
aciddegradation and in amino acid synthesis.
What form of ammonia is most favored by a normal physiological pH and which form can cross cell membranes?
NH4+ is the most abundant form of ammonia in the body and NH3 can cross cell membranes.
What are the steps of transamination?
An amino acid is converted to an alpha-keto acid which is then converted to another amino acid, which can either go back into the cycle as an alpha keto acid or continue to oxidative deamination.
What is the most common alpha keto acid?
alpha-ketoglutarate which converts to glutamate is the most common alpha keto acid.
What happens when Glutamate is oxidatively deaminated?
Glutamate is oxidatively catalyzed by glutamate
dehydrogenase that produces ammonium ion and alpha-ketoglutarate
What serves as the cofactor for oxidative deamination?
NAD+ or NADP+ can serve as the cofactor. is readily reversible; it can incorporate ammonia into
glutamate or release ammonia from glutamate.
Where in the cell does oxidative deamination occur?
This reaction occurs in the mitochondria of most cells.
What 3 enzymes can fix ammonia into organic molecules?
Glutamate dehydrogenase, glutamine synthetase, and carbamoyl phosphate synthetase I (CPSI).
Other than dietary protein, what else produces ammonia in the body?
A significant amount of NH4+ is also produced by bacteria that live in the lumen of the intestinal tract. This ammonium
ion enters the hepatic portal vein and travels to the liver.
What mechanism is used to transport amino acid nitrogen to the liver?
The alanine/glutamine cycle accomplishes this by moving carbons and nitrogen between the muscle and the liver.
What are the steps of the alanine/glutamine cycle?
- Alanine is exported by muscle where pyruvate is available.
- Pyruvate is transaminated by glutamate to form alanine, which travels
to the liver. - Upon arriving at the liver, alanine is transaminated to
pyruvate, and the nitrogen is used for urea synthesis. - The pyruvate formed is used
for gluconeogenesis, and the glucose is exported to the muscle for use as energy.
In the liver, why is glutamine
synthetase located in cells surrounding the portal vein?
Its role is to
convert any ammonia that has escaped from urea production into glutamine, so that free ammonia does not leave the liver and enter into circulation.
What are the reactions of the urea cycle?
- Synthesis of Carbamoyl phosphate
- Formation of citruline
- Synthesis of argininosuccinate
- Formation of arginine and fumarate.
- Conversion of arginine to urea and ornithine.
What two reaction of the urea cycle occur in the mitochondrial matrix? Where do the rest occur?
- Synthesis of Carbamoyl phosphate
2. Formation of citruline both occur in the mitochondrial matrix and the rest occur in the cytosol
What step of the urea cycle links it to the Krebs cycle?
The formation of arginine and fumarate from argininosuccinate. More specifically fumarate links the two cycles.
How is the urea cycle regulated by a feed-forward mechanism?
In general, the urea cycle is regulated by substrate availability; the higher the
rate of ammonia production, the higher the rate of urea formation. The urea cycle, which removes toxic compounds from the body, responds via
“feed-forward” regulation.
What is the function of the urea cycle during fasting?
During fasting, the liver maintains blood glucose levels. Amino acids from
muscle are a source for glucose by way of gluconeogenesis. As amino acid carbons are converted to glucose,
the nitrogens are converted to urea. Thus, the urinary excretion of urea
is high during fasting
What is the major amino acid substate for gluconeogeneiss?
Alanine, which is
synthesized in peripheral tissues to act as a nitrogen carrier
Release of what stimulates alanine transport into the liver?
Glucagon release stimulates alanine transport
into the liver by activating the transcription of transport systems for alanine.
What happens if there are disorders of the urea cycle?
Disorders of the urea cycle are dangerous because of the accumulation of ammonia
in the circulation. Ammonia is toxic to the nervous system.
What is the most common type of urea-cycle defect?
The most common urea-cycle defect is OTC deficiency, which is an X-linked
disorder.
What is the key energy source for skeletal muscle during catabolic states?
Oxidation of Branched Chain Amino Acids (BCAA)
What do glucogenic amino acids produce?
They produce pyruvate or Krebs cycle intermediates
What do ketogenic amino acids produce?
They produce acetyl CoA or acetoacetyl CoA
Which amino acids are purely ketogenic?
Leucine and lysine.
Which amino acids are ketogenic and glucogenic?
Tryptophan, tyrosin,phenylalanine, isoleucine, and threonine.
Which amino acids are BCAA?
Valine, leucine, and isoleucine
What is maple syrup urine disease?
This results from a defective branched-chain keto acid dehydrogenase.
What is phenylalanine a precursor to? What cofactor is required for this transition?
Tyrosine, the cofactor tetrahydrobiopterin
What is classical PKU?
A defect in the phenylalanine hydroxyls gene that inhibits conversation of phenylalanine to tyrosine.
What is Atypical PKU?
A defect in tetrahydrobiopterin reductase, which is a cofactor for converting phenylalanine to tyrosine.
What is the most oxidized form of carbon atoms on the body?
CO2 is the most oxidized form and is transferred by biotin.
What is the primary one carbon carrier in the body?
Tetrahydrofolate FH4. Which produces from the vitamin folate.
What is the “one carbon pool”?
Collectively, one-carbon groups attached to
their carrier FH4 are known as the one-carbon pool.
What are the two reactions of the body that involve B12?
It participates
in the rearrangement of the methyl group of L-methylmalonyl coenzyme A to form succinyl-CoA, and it transfers a methyl group,
obtained from FH4, to homocysteine, forming methionine.
How is SAM produced?
Produced from methionine and adenosine
triphosphate (ATP).
What does SAM do?
Transfers the methyl group to precursors that form several
compounds, including creatine, phosphatidylcholine, epinephrine, melatonin,
methylated nucleotides, and methylated DNA.
What is the only reaction in which methyl-FH4 can donate the methyl group?
Methionine metabolism is dependent on FH4 and vitamin B12.
Homocysteine, derived from methionine, can be converted
back into methionine by using both methyl-FH4 and vitamin B12.
How is the involvement of methyl-FH4 in methionine metabolism clinically relevant?
If the enzyme
that catalyzes this reaction is defective, or if vitamin B12 or FH4 levels are
insufficient, homocysteine will accumulate. Elevated homocysteine levels have been linked to cardiovascular and neurologic disease.
What are the three major structural components of FH4?
- a bicyclic pteridine ring
- a para-aminobenzoic acid
- a poly-glutamate tail
Do different forms of folate effect the types of carbon groups attached?
Yes. Different forms of folate may differ in the oxidation state of the one-carbon group, in the number of glutamate residues attached, or in the degree of oxidation of the pteridine ring.
What happens to folate in the blood?
It is loosely bound to plasma proteins particularly serum albumin.
Which amino acid is the major course of carbon for humans?
Serine
How is dietary folate absorbed?
As dietary folate pass into the proximal third of the duodenum, folate conjugated in the brush boarder of the lumen cleave off glutamate to produce the mono glutamate form of folate, which is then absorbed.
