Transcript The Cell, 5e

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
Carbohydrates are major source of calories (~40%)
• Digested by specific enzymes:
• Starch (plants) - a-amylase
• Lactose – b-galactosidase, lactase
Fig. 1 sugars
• Sucrose - sucrase
• High fructose syrup
•
Isomerized from starch
Cellulose is fiber
Glycosidases cleave carbohydrates
Overview of carbohydrate
digestion, absorption
a-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
Disaccharidases located in intestinal brush border
• Hydrolyze disaccharides
Fig. 4,5
• Anchored in membrane
•
Transmembrane N-end
• Are glycosylated
• Two enyzme activities
•
Table 1
• Ex. Sucrase-isomaltase:
• a 1,4 bond
• a 1,6; a 1,4
B-glycosidase complex
b-glycosidase complex: glycoprotein
• Anchored as phosphtidylglycan to COOH end
• Lactase hydrolyzes lactase
• Other enzyme does glycolipids (glucose-ceramide)
Fig. 10.6
Fig. 9
Fiber
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
Fig. 10
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
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
Fig. 12
Insulin and GLUT4
Insulin stimulates glucose transport into muscle
and adipose cells by increasing transporters
• Glucose goes through cells blood-brain barrier
Figs.
13,14
Synthesis of glycogen
Chapt. 28 Synthesis, degradation of glycogen
a 1.4 glycosidic, a 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
Fig. 28. 1,2
Glycogen synthesis and degradation
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 synthase
Branching enzyme
• Degradation:
Debrancher enzyme
Glycogen phosphorylase
Fig. 3
Glycogen synthesis and degradation
Glycogen has branch every 8-10 glucose residues
Synthesis:
branching helps:
solubility
more sites for synthesis
and degradation
Degradation:
Phosphorylase uses
Pi to break
Branching enzyme does
residues near branch
Branch sugar yield glucose
(not PO4)
Figs.
28.5,6
Regulation of glycogen metabolism is critical
Regulation 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
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 phosphorylase
and glucose-1-P
Fig. 11
Ch. 29 Pentose phosphate pathway, fructose, galactose
Metabolism of other sugars:
• Fructose – common in diet
•
Sucrose, high fructose corn syrup
• Galactose – from lactose
Metabolized to glycolysis intermediates
Hereditary defect diseases
• Pentose phosphate path
Forms reducing power (NADPH) for
detoxification, biosynthesis
Forms 5-C sugars for nucleotides
‘bypass part of glycolysis’
Fig. 1 fructose
Fructose
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
Fig. 3
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-glucose
Lot of galactose from Lactose; Classic galactosemic accumulates Gal-1-P
liver, impaired glycogen synthesis
Fig. 5
Pentose phosphate pathway
Pentose phosphate pathway:
• Bypass of part of glycolysis
• Generates NADPH (reducing power)
•
•
Biosynthesis fatty acids
Cholesterol, DNTP,
Detox reactions
• 5-C sugars (ribose PO4)
• Can rearrange back
into glycolysis compounds
• Regulation by cell needs
Fig. 2
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
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)
Fig. 1*
Gluconeogenesis occurs in mitochondrion and cytosol
Gluconeogenesis:
• Complex conversion of
pyruvate back to PEP
(vs. oxidation of PEP by
pyruvate kinase, PDC)
• Mitochondrion, cytosol
• Gluconeogenesis is
highly regulated
Fig. 5
Blood glucose sources
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
Fig. 20
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 disease
b. Neither child has the disease
c. Jill has the disease, not Jack
d. Jack has the diasese, not Jill
e. There is not enough information
to make a determination