Download Biochemistry Ch 37 696-706 [4-20

Biochemistry Ch 37 696-706
Protein Digestion
-digestion of protein begins in the stomach and completed in the intestine
-digestive proteins begin as zymogens secreted from their cells into digestive tract and cleaved
Digestion of Proteins in the Stomach – pepsinogen is secreted by chief cells in the stomach
-gastric acid secreted by parietal cells, which alters conformation of pepsinogen for autocatalysis
-dietary proteins denatured by stomach acid, which denatures proteins and unfold them to
make them better substrates for pepsin, which cleaves peptide bonds at various points in chain
-preferentially cleaves around aromatic or acidic amino acids
-Kwashiorkor is caused by deficiency of protein in a diet adequate in calories; children suffer
from muscle wasting and decreased plasma proteins (albumin). Leads to edema and distended
abdomen
Digestion of Proteins by Pancreatic Enzymes – exocrine pancreas acts on contents in duodenum
-pancreas secretes amylase (starch), lipase (triacylglycerol), bicarbonate (neutralizes stomach
acid and makes pancreatic enzymes active)
-pancreatic enzymes are zymogens:
pepsinogen  H+  Pepsin
trypsinogen  enterokinase (enteropeptidase)  trypsin (lysine/arginine cleavage)
chymotrypsinogen  trypsin  chymotrypsin (hydrophobic amino acid cleavage)
proelastase  trypsin  elastase (cleaves elastin and small amino acids: A, G, S)
procarboxypeptidase  trypsin  carboxypeptidase (remove AA from carboxy ends)
-trypsin/chymotrypsin/elastase are serine proteases that act as endopeptidases
-Elastase is also found in neutrophils which frequently act on the lung; elastase sometimes
released into the lung, but blocked by a-1-antitrypsin (protease inhibitor). People with mutation
in a-1-antitrypsin can lead to emphysema caused by proteolytic destruction of lung cells
-pancreas synthesizes zymogens and trypsin inhibitor in granules. Trypsin inhibitor prevents
accidental trypsin activity and destruction of exocrine pancreas
Digestion of Proteins by Enzymes from Intestine – Aminopeptidases are located on brush
border of intestine cleave one amino acid at a time from amino terminus
-digestive enzymes digest dietary proteins, sloughed off intestinal lumen cells, and themselves
into amino acids
-amount of protein digested per day is around 50-100g
Absorption of Amino Acids – Amino acids are absorbed from intestinal lumen through
secondary active Na-dependent transport systems and through facilitated diffusion
Cotransport of Na+ and Amino Acids – amino acids are absorbed from lumen of small intestine
by semispecific Na-dependent transport proteins in luminal membrane of intestinal brush
-cotransport of AA and Na is driven by low intracellular Na+ concentration
-low intracellular Na+ caused by Na/K ATPase on serosal membrane to create the
primary transport mechanism for Na gradient. Secondary transport is coupling AA to
influx of sodium
-AA are then transported to interstitial fluid by facilitated transporter in serosal membrane
-6 different cotransporters exist with specificities for different amino acids
-during starvation, intestinal epithelia take up amino acids from blood to use for energy
Hartnup Disease – autosomal recessive disorder caused by defect in transport of neutral amino
acids across intestinal and renal epithelial cells, and symptoms are caused by deficiency of
essential amino acids
Transport of Amino Acids into Cells – AA in the blood are transpoted across cell membranes of
tissues by Na-dependent cotransporters and by facilitated transporters, making it different from
glucose transport
-Na dependence ofAA transport in liver, muscle, and other tissues allow these cells to
concentrate amino acids from the blood
-trace amounts of polypeptides can enter blood through intestinal mucosa, leading to allergies
to food proteins in infants
Protein Turnover and Replenishment of the Intracellular Amino Acid Pool – intracellular amino
acid pool is generated from dietary amino acids and from degradation of existing proteins within
the cells.
-All proteins have a half-life (t1/2) that determines degradation
-if dietary protein is consumed in excess of need, it is converted to glycogen and triacylglycerols
-large amount of protein is recycled as digestive enzymes
-every day, 3x10^11 RBC die and are phagocytized and hemoglobin is degraded to amino acids
by lysosomal proteases
-6% of dietary proteins excreted each day
-proteins are recycled in cells too, decided by composition of AA, half-lives, and recycling of AA
-synthesis of many enzymes is in response to physiological demand
Lysosomal Protein Turnover – lysosomes participate in autophagy, where autophagy is a
regulated process that surrounds cytoplasm in a vesicle and delivers it to lysosome for digestion
-Cathepsin family of proteases degrades ingested proteins to individual amino acids, which can
leave lysosome and rejoin intracellular amino acid pool
-starvation of a cell triggers autophagy
-Mammalian target of rapamycin (mTOR) regulates autophagy
-mTOR INHIBITS autophagy
Ubiquitin-Proteasome Pathway – ubiquitin is a small and highly conserved protein; it targets
intracellular proteins for degradation by covalently binding to E-amino group of lysine residues
accomplished by a 3 enzyme system
-target is often polyubiquitinylated, forming long ubiquitin tails
-a proteasome complex then degrades the targeted protein and releasing intact ubiquitin that
can mark other proteins
-ATP hydrolysis is used to unfold tagged protein and push protein into the core of the cylinder
-complex is regulated by 19S regulatory particles which bind ubiquitinylated protein and deliver
them to the complex
-Many proteins have regions rich in amino acids proline, glutamate, serine, threonine and are
called PEST sequences, proteins with those are hydrolyzed by ubiquitin/proteasome
Gamma-Glutamyl Cycle – necessary for the synthesis of glutathione, a compound that protects
cells from oxidative damage, conversion of glutamineglutathione
-glutathione can reduce H2O2 and protects cells from oxidative damage, by forming oxidized
glutathione (2 glutathiones connected by a disulfide bond)