Paul J. Moughan, PhD, DSc, FRSC, FRSNZ and Bruce R. Stevens, PhD An overall concept diagram of the major aspects of protein digestion and absorption is presented in Figure 9-1, and a typical flow of protein in the adult human is shown in Figure 9-2. The normal events of digestion and absorption are grouped into phases corresponding to physiological events. The six major phases covered in this chapter primarily involve the following: 1. Gastric hydrolysis of peptide linkages in the protein 2. Digestion of protein to smaller peptides by action of pancreatic proteases, which are secreted as zymogens and activated in the lumen of the small intestine where they then carry out digestion 3. Hydrolysis of peptide linkages in oligopeptides by apical (brush border) membrane peptidases and transport of amino acids, dipeptides, and tripeptides across the brush border membrane of the absorptive enterocytes 4. Further digestion of dipeptides and tripeptides by cytoplasmic peptidases in the enterocytes 5. Metabolism of some amino acids within the enterocytes 6. Transport of amino acids across the basolateral membrane of the enterocytes into the interstitial fluid from which the amino acids enter the venous capillaries and hence the portal blood the enterocytes of the proximal small intestine (duodenum/upper jejunum). Human enteropeptidase is a heavily glycosylated protein with an N-terminal transmembrane domain and a C-terminal extracellular serine protease domain. Enteropeptidase is classified as a serine protease (or serine endopeptidase) because it has a serine residue at its active site as part of a histidine/serine/aspartate catalytic triad. A transport “system” is defined as a physiological functional unit formed from one or more transporter protein subunits. Each transporter subunit type is encoded by a specific gene. A transport system activity may result from the action of a single transporter protein or the multimeric arrangement of transporter proteins within the membrane. Although it is technically correct to use the term transporter to mean only a single protein, scientists often informally also refer to multimeric functional units as transporters. Membrane amino acid transporter systems composed of a single protein (monomeric transport systems) are listed in Table 9-1, whereas heterodimeric transporter systems for amino acids are listed in Table 9-2. TABLE 9-1 Monomeric Amino Acid Transport Systems in Human Small Intestine or Colon
Digestion and Absorption of Protein
Digestion of Protein in the Gastrointestinal Tract
Small Intestinal Luminal Phase: Activation and Action of Pancreatic Proteolytic Enzymes
Pancreatic Zymogens and their Activation Cascade
Absorption of Free Amino Acids and Small Peptides
Amino Acid Transporters in the Apical and Basolateral Membranes
TRANSPORT “SYSTEM” FUNCTIONAL NAME
COMMON ALIAS
GENE (SLC=Solute carrier)
HUMAN GENE LOCUS
TYPICAL SUBSTRATES
ION DEPENDENCY
TISSUE
EPITHELIAL MEMBRANE
SLC1 FAMILY
XAG−
EAAT3
SLC1A1
9q24
L-Glutamate, D/L-aspartate, cystine (disulfide)
H+, Na+, K+
Small intestine
Apical
ASC
ASCT1
SLC1A4
2p13-p15
Alanine, serine, threonine, cysteine, glutamine
Na+
Small intestine
Apical
ASC
ASCT2 or ATB0
SLC1A5
19q13.3
Alanine, serine, threonine, cysteine, glutamine, branched neutrals
Na+
Small intestine, colon
Apical
SLC6 FAMILY
Creatine
CRTR
SLC6A8
Xq28
Creatine
Na+, Cl−
Small intestine
Apical
GLY
GLYT1
SLC6A9
1p33
Glycine
Na+, Cl−
Small intestine
Basolateral
B0,+
ATB0,+
SLC6A14
Xq23-q24
Neutrals and dibasics, arginine, D-serine
Na+, Cl−
Colon
Apical
B0 (or B)
B0AT1
SLC6A19
5p15.33
Neutrals, glutamine
Na+
Small intestine
Apical
IMINO
SIT1
SLC6A20
3p21.6
Proline, sarcosine, pipecolate
Na+
Small intestine, colon
Apical
SLC7 FAMILY
y+
CAT-1
SLC7A1
13q12-q14
Arginine, ornithine, lysine, histidine, dibasics
None
Small intestine, colon
Basolateral
SLC15 FAMILY
Pept1
PEPT1
SLC15A1
13q33-q34
Dipeptides & tripeptides, carnosine, β-lactam antibiotics, angiotensin-converting enzyme inhibitors
H+ with NHE3
Small intestine
Apical
SLC16 FAMILY
T
TAT1
SLC16A10
6q21-q22
Aromatics, L-DOPA
None
Small intestine
Basolateral
SLC22 FAMILY
OCTN2VT
OCTN2
SLC22A5
5q23.3
L-Carnitine, acetyl-L-carnitine
Na+
Small intestine
Apical
SLC36 FAMILY
Iminoacid
PAT1
SLC36A1
5q33.1
Proline, glycine, β-alanine, GABA, taurine, D-serine
H+ with NHE3
Small intestine, colon
Apical
SLC38 FAMILY
A
SNAT2
SLC38A2
12q
Alanine, asparagine, cysteine, glutamine, glycine, histidine, methionine, proline, serine
Na+
Small intestine
Basolateral
A
SNAT4
SLC38A4
12q13
Alanine, asparagine, cysteine, glycine, threonine
Na+
Small intestine
Basolateral
N
SNAT5
SLC38A5
Xp11.23
Glutamine, histidine, serine, asparagine, alanine
Na+, H+
Small intestine (crypt cells)
Apical
SLC43 FAMILY
LAT4
LAT4
SLC43A2
17p13.3
Branched-chain amino acids, phenylalaninine
None
Small intestine
Basolateral You may also need
Digestion and Absorption of Protein
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