Chapter 18 Flashcards
What are the four amino acids that play key roles in the transport and distribution of amino acids
alanine, glutamate, glutamine, aspartate
Once proteins are broken down into amino acids what are their two potential fates
- recycled into new proteins
- oxidized for energy
______ is a hormone secreted within gastric mucosa when protein enters the stomach
Gastrin, stimulates HCl and pepsinogen
Under low pH what happens to pepsinogen ?
at low ph pepsinogen gets autocatalytically cleaved into pepson
What does pepsin do?
cuts proteins into peptides in the stomach
What hormone is secreted in the small intestine in response to low pH
secretin, it stimulates pancreas exocrine cells to secrete bicarbonate
What hormone is secreted in response to peptides entering the duodenum ?
cholecystokinin
The autocatalytic hydrolysis of pepsinogen is signaled by what
hormone gastrin and low pH
Pepsin cleaves after what amino acids
Leu, Phe, Trp, Tyr
Trypsin cleaves after what amino acids
the positively charged amino acids, Lys & Arg
Chymotrypsin cleaves after what amino acids
aromatic amino acids Phe, Trp, Tyr
How is chymotrypsin activated
by the hydrolysis of trypsin
What cleaves successive carboxyl-terminal residues
carboxypeptidase
What cleaves successive amino terminal residues
Aminopeptidases
Role of pancreatic trypsin inhibitor
protein inhibitor that protects the pancreas against self-destruction
Where are free amino acids absorbed
in the villi off the intestinal mucosa
where does oxidative deamination occur
within the mitochondrial matrix
Humans and great apes excrete both urea (from amino acids) and _______ (from purines)
we excrete urea and uric acid
Glutamate and glutamine can both be converted into _____ for use in the citric acid cycle
glutamate —-> alpha ketoglutarate
glutamine —–> alpha ketoglutarate
alanine can be converted into _____ for use in the citric acid cycle
alanine —> pyruvate
aspartate can be converted into ______ for use in the CAC
aspartate —-> oxaloacetate
Transaminations are catalyzed by _____?
aminotransferases which use the cofactor pyridoxal phosphate
oxidative deamination is catalyzed by what enzyme?
L-glutamate dehydrogenase
What is oxidative deamination positively regulated by?
ADP, low levels of glucose
What is oxidative deamination negatively regulated by?
GTP, high levels of alpha ketoglutarate
ammonia is processed into _____ for excretion
urea so it can be excreted through the urea cycle
Alpha-ketoglutarate can enter the citric acid cycle or be used for _______
gluconeogenesis
What molecule serves as an ammonia transporter
Glutamine
What does alanine aminotransferase create in the muscle and what in the liver
in muscle: creates alanine
in liver: creates glutamate and pyruvate
What makes free ammonia so toxic to the brain
Ammonia (NH4+) competes with K+ for transport into astrocytes via Na+K+ATPase , causing an elevated level of extracellular K+
The pathway by which ammonia brought to the mitochondria of hepatocytes (epithelial liver cells) is converted to urea
Urea cycle
1st nitrogen acquiring reaction of the urea cycle?
carbamoyl phosphate synthesis
- catalyzed by carbamoyl phosphate synthetase 1
What pathways link urea and citric acid cycles?
aspartate-argininosuccinate shunt
What shuttle converts aspartate to malate via oxaloacetate
the malate-aspartate shuttle
The presence of peptides in the duodenum causes the release of the blood hormone ______ which stimulates the secretion of several pancreatic proteases
cholecystokinin
Alpha-ketoglutarate can enter the citric acid cycle or be used for _______
gluconeogenesis
what enzyme catalyzes the conversion of inactive trypsinogen to active trypsin
enteropeptidase (a proteolytic enzyme secreted by intestinal cells)
Why are digestive enzymes synthesized as inactive precursors
to protect exocrine cells from destructive proteolytic attack
What does bicarbonate do in the small intestine
neutralizes gastric HCl, returning the pH to 7
All transaminases have ______ as a cofactor
PLP (pyridoxal phosphate)
In the mitochondria, glutamate undergoes oxidative deamination catalyzed by _______ to produce ________ and ________
catalyzed by L-glutamate dehydrogenase to produce alpha-ketoglutarate and NH4+
Free ammonia is combined with glutamate to yield _______ via glutamine synthetase
glutamine
Excess glutamine goes to the intestine, liver & kidneys where it is converted into _______ and _______ by glutaminase
glutamine —> glutamate + NH4+
______ can replace glutamine in the transport of amino groups from muscle —> liver in a non-toxic form
Alanine
Pyruvate and alanine are interconverted via transamination with glutamate via the enzyme __________
alanine transaminase
What is the goal of the urea cycle?
to eliminate ammonia from the body by converting it into urea
When is the expression of urea cycle enzymes increased ?
- high protein diet
- starvation, when protein is being broken down for energy
Ketogenic Amino Acids
amino acids that can be converted into ketone bodies through ketogenesis
- converted into Acetyl-CoA
Glucogenic Amino Acids
amino acids that can be converted into glucose through gluconeogenesis (and therefore pyruvate)
- all of the amino acids except Lysine, Leucine
What amino acids are exclusively ketogenic
Leucine & Lysine
What amino acids are both ketogenic and glucogenic
Phe, Try, Tyr, Isoleucine, Lysine
Carbamoyl phosphate is synthesized by carbamoyl phosphate synthetase 1 from ______ & ______
Carbamoyl phosphate is synthesized from NH4+ and HCO3- (requires 2 ATP)
What is the second nitrogen-acquiring reaction in the urea cycle ?
aspartate entry into urea cycle, performed by arginosuccinate synthetase
How is the energetic cost of the urea cycle reduced?
by cycle interconnections (ex: fumarate to malate, leading to NADH generation in the mitochondria)
What are the cofactors for the catabolism of amino acids that involve one-carbon transfers
- biotin
- tetrahydrofolate (THF)
- S-adenosylmethionine
- Pyridoxal phosphate (PLP)
What is the preferred cofactor for methyl transfer in biological reactions?
S-Adenosylmethionine
What enzyme catalyzes the conversion of serine to pyruvate
serine dehydratase, PLP dependent
Cholecystokinin stimulates the release of what pancreatic proteases
Trypsinogen
Chymotrypsin
Procarboxypeptidases A&B (the zymogens of carboxypeptidases A&B)
This cofactor functions as an intermediate carrier of amino groups at the active site of transaminases
PLP, the coenzyme form of pyridoxine (B6)
What activates carbamoyl phosphate synthase I
N-acetylglutamate which is formed by N-acetylglutamate when glutamate and acetyl CoA concentrations are high
- activated by Arginine
What two amino acids can produce oxaloacetate
Asparagine and Aspartate
Where are the branched amino acids (Leucine, Isoleucine, Valine) degraded?
NOT in the liver
- degraded in the extrahepatic tissues of the muscle, adipose, kidney, brain
What enzymes catalyze the breakdown of branched-chain amino acids into acetyl-CoA derivatives
- branched chain aminotransferase
- branched chain alpha keto acid dehydrogenase complex
Under what 3 circumstances do amino acids undergo oxidative degradation?
- Amino acids released during normal protein turnover are not needed for new protein synthesis.
- Dietary amino acids exceed the body’s needs for protein synthesis.
- Cellular proteins are used as fuel because carbohydrates are either unavailable or not properly utilized due to starvation or uncontrolled diabetes mellitus.
In transaminations, what accepts the amino group
alpha-ketoglutarate
The first step in the catabolism of most l-amino acids, once they have reached the liver, is ?
The removal of the alpha amino groups by aminotransferases
PLP is covalently bound to an enzymes active site through a _______ linkage
ALDIMINE (Schiff base) linkage to the amino group of Lysine
The first step in most PLP-catalyzed reactions is aldimine displacement. Explain
Aldimine Displacement
- the aldimine linkage to Lys is replaced by the amino group of an amino acid
What is the role of PLP in reactions at the alpha carbon such as transaminations, decarboxylation, racemizations
PLP provides resonance stabilization to the carbanion intermediates
- its highly conjugated structure allows for delocalization of the negative charge
Oxidative Deamination can use _____ or _____ as an electron acceptor
NAD+ or NADP+
What is the second major source of ammonia in hepatocyte mitochondria
Glutamine
What are the two nitrogen-acquiring reactions of the urea cycle?
- Carbamoyl phosphate synthesis
- Aspartate entry into the urea cycle by arginosuccinate synthetase
