Carbohydrate Metabolism I Flashcards by J L

Metabolism of Carbohydrates: Digestion Overview
• Simple sugars:
• Absorbed in the ____ and exported into the
circulation.

• Oligosaccharides and polysaccharides:
• Enzymatically hydrolyzed to ____ for absorption.
• Polysaccharides first digested into ____.
• Additional enzymes to complete the digestion of the
oligosaccharides to simple sugars.

small intestine
simple sugars
oligosaccharides

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Storage Polysaccharides: Starch and Glycogen

Heavily hydrated, due to the formation of hydrogen bonds bt the many exposed OH groups/water

Starch (plant cells), two types of glucose polymer:
____, ____ MW: 10^3-10^6
____, highly ____ (every ____ residues), MW up to 10^8

Glycogen (animal cells), highly ____ (every ____ residues), MW > 10^6

amylose
unbranched
amylopectin
branched
24-30
branched
8-12

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Digestion of Carbohydrates: Amylases

____
____

dextrins cannot be easily degraded by ____; they are degraded by ____ (apical border of enterocyte)

salivary amylase (alpha 1>4)
pancreatic alpha amylase
amylase
dextranase

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Dietary fiber
• Portion of the diet resistant to digestion by human digestive enzymes.
• Mainly____.
• Two categories:
• Insoluble: e.g. ____ and ____.
• Soluble: e.g. ____ (abundant in fruit), mucilages, and ____.
• Intestinal bacterial flora digests ____ dietary fiber into ____,
absorbed by the intestinal cells.

plant polysaccharides
cellulose
lignin
pectins
gums
soluble

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Dietary fiber

Carbs that cannot be attacked by ____; cannot be absorbed

the bacteria in our intestines has the capability to break down plant polysacc’s

in case of ruminants, they have the capabiltiy to break down ____

amylase

cellulose

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Glucose Metabolism

• Cell entry:
• Facilitated diffusion through \_\_\_\_.
• Rapid \_\_\_\_ by \_\_\_\_ to
Glucose 6-phosphate (G6P):
• \_\_\_\_ + Glucose > ADP + \_\_\_\_

sugar transporters (GLUT proteins)
phosphorylation
hexokinase
ATP
G6P

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Glucose Metabolism
• Rapid phosphorylation by Hexokinase to ____:

Three reasons:
G6P can not be exported through GLUT proteins: ____.
Formation of G6P reduces effective intracellular [Glc]: allows ____.

Glcextracellular ↔ Glcintracellular (+ATP) ↔ Glc-6-P + ADP

• ____ for metabolic transformations.

glucose 6-phosphate
intracellular sequestration
energized molecule

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Phosphorylation of glucose happens ____ upon entering the cell

immediately

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Glucose Metabolism
Fates of G6P:
• Glycogen \_\_\_\_
• Glucose \_\_\_\_ (liver) 
• Glycolysis
• \_\_\_\_ (PPP)

synthesis
release
pentose phosphate pathway

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Glycogen
• Glucosyl units linked by ____ bonds (linear) and ____ bonds (branching).
• Branches more frequent in the ____ of the molecule than in the ____.
• The anomeric carbon not attached to another glucosyl residue (the ____) is attached to the protein ____ by a glycosidic bond.

alpha 1,4 glycosidic
alpha 1,6 glycosidic
center
periphery
reducing end
glycogenin

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Glycogenin is not a carbon; it is actually a ____ that serves to ____ the polysaccharide

protein

anchor

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Glycogen Synthesis:
S1: Formation of ____.
S2: Synthesis of ____.
S3: Glycogen ____.

glucose 6 phosphate (G6P)
UDP-glucose
polymerization

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Glycogen Synthesis: S1, Formation of G6P and Conversion to G1P

____ catalyzes the transfer of a phosphoryl group from ATP to a variety of six- carbon sugars, including glucose and mannose.

____ isomerizes G6P to G1P.

hexokinase

phosphoglucomutase

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Phosphoglucomutase primes the molecule is order to make it available in the ____ of gluocse

linearization

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Glycogen Synthesis: S2, Synthesis of UDP-Glucose
• The hydrolysis of the phosphate bond in ____ provides the energy for the formation of UDP-glucose.
• ____, released by the reaction, is cleaved to two inorganic phosphates (Pi).

Energy provided by the ____ group in G1P is not enough; you also need the UTP

UTP
pyrophosphate (PPi)
phosphate

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UDP-glucose is a ____ molecule

By using the G1P phosphate and the UTP (three hydrolysis’); you are binding the G1P to the ____ NT

highly energized

uridine

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Glycogen Synthesis,: S3, polymerization

UDP-glucose is used to ____

Glycogen synthesis requires a ____ polymer of glycogen; the glucose from UDP-glucose is added to the ____ to extend the branch until it is very long

4,6-Transferase (cleaves ____; forms ____), when long enough cleaves part of the newly formed, long branch and transfers it to the glycogen core

polymerize
preexisting
nonreducing end
1,4
1,6

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Glycogen Synthesis: S3, Polymerization
• Glycogen synthase catalyzes the transfer of a glucose molecule to a ____ end of a glycogen molecule to form an ____.
•Requires the presence of a ____

non-reducing
alpha 1,4 linkage
primer

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Glycogen Synthesis: The Glycogenin Primer

____ is a protein which starts glycogen synthesis:
• Catalyzes its own ____.
• Glucose is transferred from UDP-glucose to a ____
residue on the enzyme/protein.
• The attached glucose chain (____ glucose molecules
minimum) can function as the ____ required for ____.

glycogenin
glycosylation
tyrosine
4
primer
glycogen synthase

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Glycogen Synthesis: Regulation of Glycogen Synthase

• Highly ____ charge distribution.
• ____ by phosphorylation.
• Phosphorylation changes the net charge of the ____ and ____ of the enzyme.
• Net charges before (green, ____, ____, ____) and after (red, ____, ____, ____) complete phosphorylation are shown.
• ____ separate sites susceptible to phosphorylation.
• Regulation of this enzyme is not binary (on/off
switching) but allows ____ modulation of activity.

asymmetric
inactivated
n-, c- terminal regions
-8, +3, -8
-12, +3, -22
nine
finely tuned

Overview of Glycogen Catabolism

D1: Production of ____.
D2: Generation of ____.

glucose 1-phosphate (G1P)

glucose 6-phosphate (G6P)

Glycogen Catabolism (Glycogenolysis): D1, Production of G1P

• ____:
• Removes a single glucose residues from a ____ end of a glycogen branch.
• Reaction resembles hydrolysis except that it is carried out in the presence of Pi
(____).
• Some of the energy of the glycosidic bond
is preserved in the ____ in G1P.

glycogen phosphorylase
non-reducing
phosphorolysis
phosphate bond

Glycogen Catabolism: D1

Glycogen pohsphorylase: ____ end; stops several residues out due to ____; what is removed is ____

4,4 Transferase: removes the remaining ____ and transfer to the ____

Alpha 1,6 glucosidase: removes the ____; this glucose is released as ____

non-reducing
sterics
G1P

1,4 linkages
core

1,6 linkage
free glucose

Glycogen Catabolism (Glycogenolysis): D2, Conversion of G1P to G6P

____ isomerizes Glucose 1-P to Glucose 6-P.
Reverse step of glycogen synthesis.

phosphoglucomutase

``` Glycogen Catabolism (Glycogenolysis): Formation of free Glucose in the ____ • Liver ____ converts Glucose 6-P into Glucose. ```

liver | glucose 6-phosphatase

Glycogenolysis in liver • Free glucose is exported from the liver into the bloodstream using the GLUT transporters • In the liver, glycogen stores serve as a source of blood glucose for the ____ .

peripheral tissues (brain)

Glycogenolysis in skeletal muscle * Muscle and most other cell types: glycogen stores serve as a ____ generation of ATP. * Muscle lacks ____ – cannot release glucose to the circulation – so shuttled into the ____.

fuel source glucose 6-phosphatase glycolytic pathway (within the same cell; never leaving)

Glycogen/Glucose Homeostasis • Synthesis of glycogen after a ____ meal when blood glucose level is elevated. • Mediated by insulin.

carbohydrate-rich

Glycogen/Glucose Homeostasis • Degradation of glycogen when blood glucose level falls (____). • Mediated by glucagon. • Liver glycogen functions as a ____: • When the blood glucose level falls, glucose is released from the liver into the ____. • Muscle lacks ____ – cannot release glucose to the circulation – so shuttled into the ____.

fasting glucostat circulation glucose 6-phosphatase glycolytic pathway

Blood glucose regulates liver glycogen metabolism: ____: first enzyme in the degradation of glycogen ____: polymerization of Glucose into glycogen Infusion of glucose into the bloodstream: --inactivation of ____ --activation of ____ in the liver Mediated by insulin as primary signal for glycogen synthesis Phosphorylase: --____ in liver cells --binding of glucose to activate phosphorylase (a form) shifts its allosteric equilibrium to the ____

``` glycogen phosphorylase glycogen synthase glycogen phosphorylase glycogen synthase glucose sensor inactive b form ```

Glycogen Breakdown and Synthesis Are Reciprocally Regulated The Insulin cascade promotes glycogen synthesis and inhibits glycogen catabolism: 1. Binding of insulin to its receptor activates ____. 2. PP1 dephosphorylates the inactive ____ thereby converting it to the active ____, stimulating glycogen synthesis. 3. PP1 also dephosphorylates active ____, thereby converting it to the inactive ____. 4. PP1 inactivates Phosphorylase Kinase (thus preventing activation of Glycogen Phosphorylase; see next slide). 5. Because of the inhibition of ____ and the activation of ____, glycogen is synthesized.

``` protein phosphatase 1 glycogen synthase b glycogen synthase a glycogen phosphorylase a glycogen phosphorylase b glycogen phosphorylase glycogen synthase ```

Glycogen Breakdown and Synthesis Are Reciprocally Regulated The cAMP cascade promotes glycogen catabolism and inhibits glycogen synthesis: 1. Glucagon or epinephrine activate ____ which synthesizes cAMP from ATP. 2. Binding of cAMP activates ____ (cAMP- dependent protein kinase). 3. PKA activates ____ by phosphorylation. 4. Phosphorylase Kinase phosphorylates inactive ____, thereby converting it to the active ____. 5. PKA also phosphorylates ____ to convert it to the inactive ____, preventing glycogen synthesis. 6. Because of the inhibition of ____ and the activation of ____, glycogen is degraded.

``` adenylate cyclase protein kinase A phosphorylase kinase glycogen phosphorylase b glycogen phosphorylase a glycogen synthase a glycogen synthase b glycogen synthase glycogen phosphorylase ```

Overview of glycolysis: two phases: ____ and ____

preparatory phase | payoff phase

Overview of Glycolysis: Bioenergetics • In glycolysis, a molecule of glucose is degraded in a series of enzyme-catalyzed reactions to yield two molecules of ____. • During the sequential reactions of glycolysis, some of the free energy released from glucose is conserved in the form of ____ and ____.

pyruvate ATP NADH

Glycolysis: Conversion of Glucose 6-phosphate to Fructose phosphates ____ ____: 2nd priming reaction

isomerization | phosphorylation

Glycolysis: Cleavage of Fructose 1,6-bisphosphate to the Triose phosphates • Fructose-1,6-bisphosphate (6-carbon sugar) is cleaved into two 3-carbon molecules: • ____. • ____. • Reaction is mediated by an ____. • An ____ then converts DHAP into G3P (a triose).

dihydroxyacetone phosphate (DHPA) glyceraldehyde 3-phosphate (G3P) aldolase isomerase

Glycolysis: Oxidation and Phosphorylation of Glyceraldehyde-3-Phosphate G3P oxidation to 1,3-Bisphosphoglycerate by a ____ Released free energy (deltaG) from ____ is conserved as reduced NADH + H+: first ____

dehydrogenase oxidation payoff reaction

Glycolysis: Oxidation and Phosphorylation of Glyceraldehyde-3-Phosphate NAD (____) is the coenzyme of the G3P dehydrogenase The B3 vitamin, ____, is involved in the redox reaction NADH must be regenerated to ____ for glycolysis to proceed

nicotinamide adenine dinucleotide niacin NAD+

Glycolysis: Formation of 3-phosphoglycerate ____: one phosphate group from 1,3-Bisphosphoglycerate is used to phosphorylate ADP to form ATP - ____ The reaction is mediated by a ____ Since 2 triose phosphates are produced from one hexose molecule > ____ are generated in this step

2nd payoff reaction substrate level phosphorylation kinase 2 ATPs

Glycolysis: Formation of Pyruvate • The lower-energy phosphate on carbon-3 in 3-PG is moved to a higher-energy bond in carbon-2 by two sequential reactions: --- Conversion of 3-PG to 2-PG by a ____. --- Dehydration (loss of water molecule) of 2-PG to form Phosphoenolpyruvate (PEP) by an ____. • PEP is a high-energy compound that can drive the synthesis of ATP from ADP: ____. --- The reaction is catalyzed by the enzyme ____. • As a result of this reaction, ____ are formed/glucose.

``` mutase enolase 3rd payoff reaction pyruvate kinase 2 ATPs ```

Alternative Fates of Pyruvate and Regeneration of NAD+ A. Pyruvate is metabolized in the ____, and the reducing power of ____ is used to synthesize ____ in the mitochondria. B. Fermentation to lactate in vigorously contracting muscle, in erythrocytes, in some other cells, and in some microorganisms: ____ and ____ form lactate, regenerating ____. C. In yeast and other microorganisms, pyruvate is converted to ____.

TCA (Krebs) cycle NADH ATP NADH pyruvate NAD+ ethanol

Fructose Metabolism • Conversion of Fructose to DHAP + G3P in red. – These two compounds are intermediates of ____ and are converted in the ____ principally to glucose, glycogen, or fatty acids. • In the liver, ____ cleaves both ____ in the pathway for fructose metabolism and ____ in the pathway for glycolysis.

``` glycolysis liver aldolase B fructose 1-phosphate fructose 1,6-bisphosphate ```

Regulatory Mechanisms in Glycolysis • Major control points in skeletal muscle and peripheral tissues: • Hexokinase: --- Feedback inhibition: ____. • Phosphofructokinase-1: --- Allosteric regulation: ____, Fructose-2,6-bisP. • Feedback inhibition: ____ (from the TCA cycle). • The regulation shown for ____ occurs only for the ____ (L) isoenzyme: --- Allosteric regulation: ____, Fructose-2,6-bisP. • Systemic (hormonal) regulation: --- Glucagon, Insulin.

``` Glc6P ATP/AMP ratio citrate pyruvate kinase liver ATP ```

Coordinated Regulation of Glucose Metabolism: PFKs • ____ regulates glycolysis: • ____ by AMP (low energy charge). • ____ by ATP (high energy charge) • ____ by citrate (TCA cycle less active). • ____ produces fructose-2,6-bisphosphate which ____ activates ____.

``` PFK-1 activated inhibited inhibited PFK-2 allosterically PFK-1 ```

The Pentose Phosphate Pathway (PPP) Two phases: • Oxidative: --- Generates ____ for biosynthesis reactions requiring reducing equivalents. --- Generates ____ for nucleotide biosynthesis (e.g.for DNA, RNA). • Non-oxidative: ---Recycles ____ molecules of pentose into five molecules of ____, to continue production of NADPH and converting Glucose 6-P (in six cycles) to ____.

NADPH ribose 5-P six glucose 6-phosphate CO2

Oxidative Phase of the Pentose Phosphate Pathway Glucose 6-P is ____ to a pentose (Ribulose 5-P) in 3 steps - -- 2 ____ are reduced to 2 ____ - -- 1 ____ is released (decarboxylation) Ribulose 5-P is ____ to Ribose 5-P - -- ribose 5-P can enter the ____; or - -- converted into glycolytic intermediaries (____)

oxidatively decarboxylated NADP+ NADPH CO2 isomerized nucleotide synthesis pathway non-oxidative PPP

Non-oxidative Phase of the Pentose Phosphate Pathway Based on reversible reactions: - -- If there no need for nucleotide biosynthesis: - ---- ribose 5-P converted into ____

glycolytic intermediaries

Non-oxidative Phase of the PPP Based on reversible reactions: If low NADPH: - -- Ribose 5-P is converted into ____ through ____ intermediary non-oxidative reaction - -- Recycles six ____ into five ____ (G6P), to continue production of ____ and converts G6P (in six cycles) to ____

``` G6P 4 pentoses hexoses NADPH CO2 ```

Non-oxidative phase of the PPP Based on reversible reactions: If high NADPH and there is need for nucleotides: - -- inhibition of ____ - -- fructose 6-P and glyceraldehyde 3-P used for ____

oxidative pathway | ribose 5-P synthesis