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