Chapts 27-31 topics Chapts. 27-31 Carbohydrate topics Student Learning Outcomes : Explain basic...
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Transcript of Chapts 27-31 topics Chapts. 27-31 Carbohydrate topics Student Learning Outcomes : Explain basic...
Chapts 27-31 topics
Chapts. 27-31 Carbohydrate topics Student Learning Outcomes:• Explain basic processes of digestion, absorption and
transport of carbohydrates (and lactose intolerance)
• Describe formation, degradation of glycogen
• Describe essentials of other sugar metabolism:• Pentose phosphate path, fructose, galactose
• Describe the basic path of gluconeogenesis
Chapt. 27 Carbohydrates digestion
Fig. 1 sugars
Carbohydrates are major source of calories (~40%)• Digested by specific enzymes:• Starch (plants) - -amylase• Lactose – -galactosidase, lactase• Sucrose - sucrase• High fructose syrup
• Isomerized from starch
Cellulose is fiber
Glycosidases cleave carbohydrates
Overview of carbohydrate digestion, absorption-amylases (saliva, pancreas)
• Saliva starts breakdown• Pancreatic enzyme in intestine
• Disaccharidases in intestine• Monosaccharides enter blood through intestinal epithelium
facilitative diffusion transporters or Na+-dependent glucose transporters
• Fiber and remaining compounds digested by bacteria in colon
Fig. 2
Disaccharidases
Fig. 4,5
Disaccharidases located in intestinal brush border• Hydrolyze disaccharides• Anchored in membrane
• Transmembrane N-end
• Are glycosylated• Two enyzme activities
• Table 1
• Ex. Sucrase-isomaltase:• 1,4 bond• 1,6; 1,4
-glycosidase complex
Fig. 9
-glycosidase complex: glycoprotein• Anchored as phosphtidylglycan to COOH end• Lactase hydrolyzes lactase• Other enzyme does glycolipids (glucose-ceramide)
Fig. 10.6
Fiber
Fig. 10
Fiber is indigestible carbohydrates• Colonic bacteria metabolize leftover saccharides
• Generate gas (H2, CO2, CH4)
• Lactate• Short fatty acids
• Acetic, butyric• Some absorbed by body• Incomplete digestion
products lead to diarrhea
Lactose intolerance
Lactose intolerance: (see Table 2)
• Low levels lactase (late-onset) • Adult levels are low in many populations
• Injestion of lactose → pain, nausea, flatulence, diarrhea
• Can mix lactase enzyme with food first
Absorption of sugars
Fig. 12
Sugars are absorbed through intestinal epithelia:• Glucose through Na+-dependent transporters:
• let in Na+ and glucose, galactose also (can concentrate)
• Glucose through facilitated transport (GLUT 1-5)• Different isoforms• 12 membrane-spans
• Fructose and galactose
Use glucose transporters
Insulin and GLUT4
Figs. 13,14
Insulin stimulates glucose transport into muscle and adipose cells by increasing transporters
• Glucose goes through cells blood-brain barrier
Synthesis of glycogen
Fig. 28. 1,2
Chapt. 28 Synthesis, degradation of glycogen 1.4 glycosidic, 1,6 branches,
• protein glycogenin on end• Major role in liver is blood glucose• Major role in muscle is ATP• Some people have defects glycogen metabolism
Glycogen synthesis and degradation
Fig. 3
Different enzymes for synthesis, degradation• Starts and ends with glucose-1-Phosphate• Careful regulation• Synthesis:
UDP-G pyrophosphorylase costs 1 UTP (2 P~P) each UDP-G other paths
Glycogen synthaseBranching enzyme
• Degradation:
Debrancher enzyme
Glycogen phosphorylase
Glycogen synthesis and degradation
Figs. 28.5,6
Glycogen has branch every 8-10 glucose residues
Synthesis:branching helps: solubility more sites for synthesis and degradation
Degradation:Phosphorylase uses Pi to breakBranching enzyme does residues near branchBranch sugar yield glucose
(not PO4)
Regulation of glycogen metabolism is criticalRegulation of glycogen in liver:• responds to hormones glucagon, epinephrine via cAMP, PKA
Reciprocal phosphates activate, inhibit:
• Glycogen synthase PO4 inhibit
• Phosphorylase kinase• Glycogen phosphorylase PO4 activates
• Phosphatases remove PO4
Dotted lines decreased in fasting state
Fig. 8
Muscle glycogenolysis
Fig. 11
Exercise activates muscle glycogenolysis:Initiated by muscle contraction, nerve impulse or epinephrine• AMP allosteric activator of glycogen phosphorylase (Fig. 9.8)
• Nerve signal Ca2+ release, binds calmodulin (Fig. 9.10)Activates phosphorylase kinase
• Epinephrine through PKA activates same phosphorylase kinase
Result: active PO4
Glycogen phosphorylaseand glucose-1-P
Ch. 29 Pentose phosphate pathway, fructose, galactose
Fig. 1 fructose
Metabolism of other sugars: • Fructose – common in diet
• Sucrose, high fructose corn syrup
• Galactose – from lactoseMetabolized to glycolysis intermediates Hereditary defect diseases
• Pentose phosphate pathForms reducing power (NADPH) for
detoxification, biosynthesisForms 5-C sugars for nucleotides‘bypass part of glycolysis’
Fructose
Fig. 3
Fructose is metabolized to intermediates of glycolysis
• Fructokinase forms F-1-PO4
Essential fructosuria people lack enzyme• Aldolase critical: 3 isoforms All do glycolysis F 1,6-P
Only Aldolase B Cleaves F-1-P Hereditary fructose intolerance: can be fatal: accumulate F-1-P in liver impaired gluconeogenesis, glycogenolysis; hypoglycemia
Galactose
Galactose is converted to Glucose-1-P• Galactokinase forms Gal-1-P• Galatose 1-P uridylyltransferase forms Glucose 1-P uses UDP-glucose and forms UDP-galactose• Epimerase can regenerate UDP-glucoseLot of galactose from Lactose; Classic galactosemic accumulates Gal-1-P
liver, impaired glycogen synthesis
Fig. 5
Pentose phosphate pathway
Fig. 2
Pentose phosphate pathway: • Bypass of part of glycolysis• Generates NADPH (reducing power)
• Biosynthesis fatty acidsCholesterol, DNTP,
• Detox reactions
• 5-C sugars (ribose PO4)
• Can rearrange back into glycolysis compounds• Regulation by cell needs
Gluconeogenesis essentials
Gluconeogenesis in the liver makes glucose:
• Critical need for glucose especially red blood cell, brain• During fasting, liver mobilizes
glycogen, makes new glucose from noncarbohydrates
• (see also Chapters 1-3)
Fig. 2
Gluconeogenesis
Fig. 1*
Gluconeogenesis:• Main precursors are lactate, glycerol, amino acids• Many steps are reversals of
glycolysis reactions• 3 critical irreversible steps have separate enzymes (these also regulated)
Gluconeogenesis occurs in mitochondrion and cytosol
Fig. 5
Gluconeogenesis:• Complex conversion of
pyruvate back to PEP(vs. oxidation of PEP by
pyruvate kinase, PDC)• Mitochondrion, cytosol
• Gluconeogenesis is highly regulated
Blood glucose sources
Fig. 20
Sources of blood glucose in fed, fasting, starved• Liver uses glycogenolysis• Muscle uses its glycogen, not contribute to blood
level (lack G-6-Phosphatase)• Gluconeogenesis spares
body protein
Review question Chapt 27
After digestion of a piece of cake that contains flour, milk and sucrose as its primary incredients, the major carbohydrate products that enter the blood are which of the following:
a. glucose
b. fructose and galactose
c. galactose and glucose
d. fructose and glucose
e. glucose, galactose and fructose
Review question Ch. 29
29.1 Hereditary fructose intolerance is a rare recessive genetic diseases that is most commonly caused by a mutation in exon 5 of the aldolase B gene. The mutation creates a new AhaII recognition sequence. To test for the presence of the disease, DNA was extracted from parents and their two children; After PCR and enzyme digestion, DNA run on gel:
Which conclusion can be made:a.Both children have the diseaseb.Neither child has the diseasec.Jill has the disease, not Jackd.Jack has the diasese, not Jille.There is not enough information to make a determination