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