Marks’ Biochemistry Ch 27 – Carbohydrates A Review.
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Transcript of Marks’ Biochemistry Ch 27 – Carbohydrates A Review.
Marks’ Biochemistry
Ch 27 – CarbohydratesA Review
Dietary Carbohydrates• Largest source of calories in US• Plant starches
– In grains, tubers, veggies– Amylopectin
• Straight-chain glycosyl α1,4, branched α1,6
– Amylose• Straight-chain glycosyl α1,4
– Fruits/veggies• Sucrose and fructose
– Fiber• Not digested• Plant polysaccharides and lignan
• Animal starches– Small amounts glycogen and glycolipids– Major dietary from animals = LACTOSE
• Glucose are NOT required– Can be synthesized– Fructose, galactose, xylulose synthesized from glucose
Carbohydrate Digestion
• Key: digest carbs to their monosaccharide counterparts!!!
• Some specificty per digestive enzyme• α-amylase
– Begins in mouth• Forms α-dextrin
– Endoglucosidase (internal α1,4)– Stomach pH inactivates– Bicarb and more enzyme released from
pancreas to breakdown• Maltose (di)• Maltotriose (tri)• Oligosaccharides = limit dextrans (4-9
glucosyl units)
Monosaccharides
Salivary/Pancreatic Amylase Activityα1,4 glucose
Little/no activity α1,6/end α1,4
No effect sugars other than glucose w/ α1,6
↓pH
stomachinactive
shortened
Limit dextrans4-9 glucosyl uits1+ α1,6 bonds
Bicarb and
reactivated
Amylase Activity
• Reduced in– EtOH-induced pancreatitis– Surgical removal– Cystic fibrosis• Mucus blocks pancreatic duct• Exocrine pancreas reduced 10%
– Still may not affect rate starch digestion– Excessive secretion
• Protein/fat digestion more strongly affected
Starch Blockers
• Marketed for losing weight• Based on bean proteins– Block amylase
• Never shown effective in aiding weight loss– Excess amylase production– Low stomach pH
• Recently from wheat– More work required
Brush Border
• Dietary disaccharides– Lactose– Sucrose
• Products starch digestion
• Glycosidases in intestinal brush border cells digest these into monosaccharides– Display some homogeneity
Glucoamylase
• Two globular domains– Each w/catalytic site
• Exoglucosidase– Begins at non-reducing ends α1,4– Release glucose– Stops at α1,6• Limit dextran down to isomaltose
• Activity progressively ↑ along small intestine
Highest activity = ileum
Sucrase-Isomaltase Complex
• Inserted through membrane• Protrudes through lumen• Intestinal protease clips to 2
attached units• 100% hydrolyze sucrose• 80% hydrolyze maltose• Activity at α1,6
– Whatever glucoamylase can’t get, this enzyme can!
Highest activity = jejunum
2 separate units
Putting it all together…
Sucrase-Isomaltase Complex Deficiency
• “Sucrose intolerance”• Digest normal amounts of starch w/o
problems– Maltase activity of glucoamylase– Residual activity of S-I complex
Trehalase
• Only 1 catalytic site• Hydrolyzes trehalose bond• Not major dietary in US
– Insects– Algae– Mushrooms– Other fungi
• Inadvertently eat and deficiency– Nausea– Vomiting– Other severe GI
β-Glycosidase Complex
• Aka Lactase-Glucosylceramidase• Again, 2 catalytic sites• Very different structure– Phosphatidylglycan anchor
• Lactase– Hydrolyzes β-bond connecting galactose and
glucose• Glucosylceramidase– Hydrolyzes β-bond b/w glucose and ceramide
Highest activity = jejunum
Indigestible Carbs
• High in amylose• Less hydrated• Colonic bt have
at it!– H2, CO2, CH4
(flatus)– Short-chain fatty
acids (SCFA)– Lactate
• We can absorb the SCFA and lactate for energy use
Lactase Deficiency
• Nonpersistant– Increases 6-8 weeks– Rises gestational (27-32 weeks)– High 1 month post-partum and declines– Decreases adult levels 5-7 years– Adult hypolactasia
• Normal condition everywhere ELSE• Again think flatulence, diarrhea and H2 = avoidance
• Nations with “milk-dependency” means lactase remain or slightly above infant levels
Lactase Deficiency
• Intestinal injury– Injury to absorptive cells diminish lactase– Secondary lactase deficiency
• Kwashiorkor• Colitis• Gastroenteritis• (Non)tropical sprue• Excessive EtOH
– Other enzymes present at excessive levels– First to be lost, last to recover
Dietary Fiber• Insoluble fiber
– Plant polysaccharide and lignan• Cellulose• Hemicellulose• lignins
• H2O-soluble fiber• Pectins• Mucilages• Gums
– Bt flora can metabolize• Gas and SCFA (for energy!)
• 25-38 g/day; 14g fiber per 1000 cal• Disease preventive soluble fibers
– Lower cholesterol– Binding bile acids– Oats contain β-glucan
• ↓bile resorption
– Pectin for DM• ↓ rateabsorption
• ↓blood glucose postprandium (after meals)
Sugar Absorption
• Sugars have tendency to raise blood sugar• Either near-immediate raise or slowly raise• High glycemic index– Cornflakes– Potatoes
• Low glycemic index– Skim milk– yogurt
Facilitative Transport
• Glucose is polar– Cannot diffuse across membranes
• On serosal surface– No energy expenditure!– Facilitates transport (ha, gotcha) into capillaries– Referred to as GLUT1-5
• All have 12 membrane-spanning domains
• Luminal surface too• Fructose too
– Facilitated through GLUT family– Can transport glucose, but higher affinity for
fructose• Galactose as well
Na+-dependent Transport
• Luminal side– Requires energy (Na/K-ATPase pump)– Cotransport of Na+ and glucose = symport!– Galactose too
GLUT Mechanism
• Differ among tissues– Depend on fx glucose, tissue-
specific– Mostly, rate transport NOT rate-
limiting– Isoform low Km for glucose– Or present [high]
GLUT Mechanism• GLUT1
– RBC aka erythrocyte– Km 1-7mM– Present extremely [high]– When glucose falls postprandial, glucose still adequate
• GLUT2– Liver Km relatively high– Maintenance blood glucose
• GLUT4– Adipose
• Insulin increases availability• FA and glycerol synthesis from glycolysis
– Skeletal mm• Transport by insulin• Availability for glycolysis, glycogen synthesis
Neural Glucose Transport• Hypoglycemic when glucose 18-54mg/dL• Decreased supply to brain
– Light-headed– Dizziness– Progressive into coma
• Slow rate transport = BBB• Tight junctions
– Must pass• Blood• CSF by GLUT1• Basement membrane• Finally brain by GLUT3
• Km of brain 7-11mM• Vm not much greater than rate glucose
utilization– Below fasting of 80-90mg/dL– Significant effects
Deria Voider
• Either reduction or complete avoidance• GI discomfort from inability digest lactose• Symptomatic >25g lactose ingested• Yogurt = bt lactase• Hard cheese = ↓lactose• However milk (products) good source of Ca2+
= supplement or could lead to osteoporosis• Lactose also in meds
Ann Sulin• Poorly controlled DB• Hyperglycemia• Lack of insulin = lack of glucose uptake GLUT4• Accumulates in blood
– Glycosylation end products– HbA1c– AGEs
• Important to add fibers to diet– Delay gastric emptying– Retard rate absorption
• Reduces rate blood glucose rises
• Should consume low glycemic index foods– Eat pasta and rice– Not potatoes– Incorporate breakfast cereals
Nona Melos• Inability digest sucrose/absorb fructose• Converted to gas by colonic bt• Stool pH 5, positive test for sugar• H2-breath test
– Non-portable device gas chromotagraphy– Electrodes measure current
• Deficiency in S-I complex– No fx reduction in maltase (glucoamylase)
• Urine negative test for sugar– Not absorbing, no chance to get into blood and thus to be reabsorbed by
kidney• Jejunal biopsy
– Lactase, sucrase, maltase, trehalase normal– Enzymes for fructose normal range
• Requires diet free fruit juices, other foods with fructose
Vibrio cholerae• Gram (-)• Enter water source
– Poverty– Plumbing primitive/nonexistant
• Attach brush border– Release exotoxin– ↑cAMP– Na+, anions, H2O not absorbed– Cl-, cations secreted
• Diarrhea can be deadly if >1L/hour• Na-dependant transporters NOT affected
– Co-admin glucose and Na+– Partially correct fluid loss– Also Na+ and amino acid co-admin
“Rice water” stool