Protein Metabolism Flashcards
Protein Metabolism: Overview
• Dietary proteins are digested to amino acids.
• Amino acids are absorbed by the ____ cells.
• Amino acids are used to synthesize proteins and other
nitrogen-containing substances.
• Carbon skeletons can be ____ for energy.
• Excess nitrogen must be ____.
intestinal
oxidized
excreted
catabolism of AA branches into other branches of cellular metabolism: connection with ____, with ____ (formation of glucose), metabolism of ____
metabolism of AA is highly ____
the primary use of AA obtained from diet is to build new ____; but they are also used in other branches
important part of metabolism of AA > to get rid of the amino groups > formation of ____ (waste product)
TCA
gluconeogenesis
FA
integrated
proteins
urea
Initial Digestion of Dietary Proteins
• Sequential action of ____ and ____: free amino acids, di- and tripeptides.
• ____ epithelial cells absorb the amino acids and small peptides using specific transporters.
• Amino acids are exported to the ____.
proteases
peptidases
intestine
circulation
digestive system provides a series of proteases (cut ____) and peptidases (cleave fragments of proteins that are ____) into 2,3 or free single monomer AA
at the level of ____ > absorption of AA takes place
digestion of protein begins at ____, but the bulk of proteases is produced by the ____
big proteins
<20 AA
small intestine
stomach
pancrease
Protection of the Pancreas from Self-Digestion
• The pancreas stores ____ in secretory granules: – All zymogens are inactive until they are cleaved by ____.
• The pancreas also synthesizes and stores trypsin inhibitor:
– Protein that binds to and inhibits ____
• Trypsin inhibitor inhibits any trypsin accidentally activated (by ____ from trypsinogen) inside the pancreas.
zymogens
trypsin
trypsin
self-cleavage
Protection of the Pancreas from Self-Digestion
Conversion of trypsinogen to trypsin is the removal of the ____ (green). The pink residue is the new N-terminus, which becomes ____ in the native structure.

N-terminal 6 AA
buried
Activation of the Gastric and Pancreatic Zymogens
• Pepsinogen self-cleavages by the ____ of the stomach.
• Trypsinogen is cleaved by ____ in the ____ to form the active protease trypsin
- Trypsin then catalyzes the cleavage and activation of the other ____
low pH
enteropeptidase
intestine
pancreatic zymogens
digestion of proteins begins in ____
only protease in stomach = ____; environment here is very acidic, so this zymogen is activated by low pH
____ houses the rest of the proteases (rest of digestion of food); they are all secreted by the ____
they do not become active until trypsinogen finds ____ (produced by epi of SI) > cascade now begins
enteropep cleaves the greeen AA > activates trypsin > now cleaves the rest of the ____
stomach
pepsin
small intestine
pancrease
enteropeptidase
pancreatic enzymes
Action of the Digestive Proteases
• Act in ____: no single protease can fully digest a protein.
• Serine endoproteases:
– Release small polypeptides by cleaving ____ sites of a protein chain.
– Trypsin is most specific (only cleaves after ____ or ____).
• Exoproteases:
– Release single amino acids from the ____ of a polypeptide.
– Aminopeptidases remove the amino acid at the ____. – Carboxypeptidases remove the amino acid at the ____.
concert
internal
Arg
Lys
end
N-terminus
C-terminus
Action of Digestive Proteases
____ are more specific than ____ (____ can cleave any AA)
action of these enzymes: the protein products reaching the enterocytes in the epi are mono, di, or tri peptides (at the ____ will cleave 2/3 peptides)
carboxypeptidase
aminopeptidases
aminopeptidases
surface of the cell
Absorption of Amino Acids
• Amino acids are absorbed from the lumen of the intestine via ____- specific ____.
• The co-transport 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 ____:
– The low intracellular [Na+] is maintained by the ____.
- On the basal side, the amino acid is carried down its concentration gradient into the blood via a ____.
- Most subsequent amino acid metabolism takes place in the ____
semi
Na+-dependent co-transport
Na+ concentration
Na+/K+ ATPase active transporter
facilitated transporter
liver
Absorption and Metabolism of Amino Acids
• Intestine:
— Amino acids released by digestion of dietary proteins travel through the ____ to the liver.
• Liver:
— Amino acids are used for the synthesis of
proteins.
— Or converted to ____ or ____.
— Glucose is stored as ____ or released into the blood.
• Amino acids that pass through the liver are converted to proteins in cells of other tissues.
hepatic portal vein
glucose
TAG
glycogen
Biosynthesis of the Non-Essential Amino Acids
• The C-skeletons of ____ amino acids may be produced from glucose through intermediates of glycolysis or the TCA cycle.
• But not any of the ____ amino acids:
– Ile, Thr, Leu, Met, His, Val, Trp, Lys, Phe.
10
9 essential
Biosynthesis of the Non-Essential Amino Acids
the initial steps integrate the metabolism of AA w/ ____; the synthesis of AA themslves are very long themselves, but the ____ steps are highly integrated with the metabolism of carbs
some of the initial synthesis of AA (and final products) are quite simple (TA, GDH, TA) > VERY IMPORTANT STEPS > involved in the degradation and the production of ____ (TA = transamuriation, gluccodehydrogenaase activity = GDH)
carbohydrates
initial
urea
Amino Acid Metabolism: Basic Chemical Transformations
• For each amino acid there is a corresponding ____ or ____.
the only difference is that an amino group on an AA is switched with a ____ (on the keto acid/C-skeleton)
keto-acid
C-skeleton
ketone group
Basic Chemical Transformations : 1. Transamination
• ____: major process for removing N
from amino acids.
• The amino group from one amino acid is transferred to another:
– Pairs of amino acids and their corresponding α-keto acids are involved.
– Reactions are ____.
– ____ as a cofactor.
– The enzymes are called ____ or ____.
• Panel A: generalized reaction.
– An amino acid is converted to its corresponding α-keto acid.
transamination reversible pyridoxal phosphate (PLP; vitamin B6) transaminases aminotransferases
The (Simplified) Transamination Mechanism
Transamination reactions proceed through a ____* using pyridoxal phosphate (Vitamin B6) as a ____:
- = Ping-pong mechanism, also called a ____, is characterized by the change of the enzyme into an ____ when the first substrate-to-product reaction occurs.
transaminases > takes an amino group from an AA > amino group converts the ___ in the vitamin to an ____ group; then it transfer the amino to the ____
“ping pong” mechanism
cofactor
double-displacement reaction
intermediate
aldehyde group
amino
second AA
Basic Chemical Transformations : 1. Transamination
• Panel B: The aspartate transaminase reaction.
– N is transferred as an amino group from an amino acid to an α-keto acid to form a ____ amino acid.
• All amino acids except ____ and ____ can undergo transamination reactions.
aspartate > transaminase acts on aspartate and alpha ketglutarate (the keto carbon of the 2nd AA)
the enzyme transfers the amino to the keto skeleton, which then produces ____ (a different AA) > which you then produce the keto group for ____ (OAA)
different lysine threonine glutamate aspartate
Transaminations in AA Biosynthesis
Cmmon Keto Acids <> Selected Amino Acids
pyruvate <> ____
oxaloacetate <> ____
____ <> glutamate
alanine
aspartate
alpha-ketoglutarate
Basic Chemical Transformations : 2. Oxidative Deamination
• Glutamate can undergo ____ to alpha-ketoglutarate and NH4+:
– Catalyzed by ____.
– Freely ____.
• Glutamate can collect N from other amino acids (via ____) and then release ammonia through the glutamate dehydrogenase reaction.
• Several other amino acids can be directly deaminated, but these reactions are ____:
– The main chains of serine and threonine by B6- dependent ____.
– The main chain of histidine by ____.
– The side chains of arginine and glutamine by ____ and ____.
oxidative deamination
glutamate dehydrogenase
reversible
transamination
irreversible serine dehydratase histidine deaminase arginine glutamine deaminases
