Carbohydrate Metabolism I Flashcards

1
Q

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.

A

small intestine
simple sugars
oligosaccharides

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2
Q

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

A
amylose
unbranched
amylopectin
branched
24-30
branched
8-12
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3
Q

Digestion of Carbohydrates: Amylases

____
____

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

A

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

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4
Q

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.

A
plant polysaccharides
cellulose
lignin
pectins
gums
soluble
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5
Q

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 ____

A

amylase

cellulose

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6
Q

Glucose Metabolism

• Cell entry:
• Facilitated diffusion through \_\_\_\_.
• Rapid \_\_\_\_ by \_\_\_\_ to
Glucose 6-phosphate (G6P):
• \_\_\_\_ + Glucose > ADP + \_\_\_\_
A
sugar transporters (GLUT proteins)
phosphorylation
hexokinase
ATP
G6P
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7
Q

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.

A

glucose 6-phosphate
intracellular sequestration
energized molecule

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8
Q

Phosphorylation of glucose happens ____ upon entering the cell

A

immediately

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9
Q
Glucose Metabolism
Fates of G6P:
• Glycogen \_\_\_\_
• Glucose \_\_\_\_ (liver) 
• Glycolysis
• \_\_\_\_ (PPP)
A

synthesis
release
pentose phosphate pathway

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10
Q

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.

A
alpha 1,4 glycosidic
alpha 1,6 glycosidic
center
periphery
reducing end
glycogenin
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11
Q

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

A

protein

anchor

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12
Q
  • Glycogen Synthesis:
  • S1: Formation of ____.
  • S2: Synthesis of ____.
  • S3: Glycogen ____.
A

glucose 6 phosphate (G6P)
UDP-glucose
polymerization

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13
Q

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.

A

hexokinase

phosphoglucomutase

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14
Q

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

A

linearization

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15
Q

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

A

UTP
pyrophosphate (PPi)
phosphate

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16
Q

UDP-glucose is a ____ molecule

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

A

highly energized

uridine

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17
Q

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

A
polymerize
preexisting
nonreducing end
1,4
1,6
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18
Q

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 ____

A

non-reducing
alpha 1,4 linkage
primer

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19
Q

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 ____.

A
glycogenin
glycosylation
tyrosine
4
primer
glycogen synthase
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20
Q

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.

A
asymmetric
inactivated
n-, c- terminal regions
-8, +3, -8
-12, +3, -22
nine
finely tuned
21
Q

Overview of Glycogen Catabolism

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

A

glucose 1-phosphate (G1P)

glucose 6-phosphate (G6P)

22
Q

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.

A

glycogen phosphorylase
non-reducing
phosphorolysis
phosphate bond

23
Q

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 ____

A

non-reducing
sterics
G1P

1,4 linkages
core

1,6 linkage
free glucose

24
Q

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

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

phosphoglucomutase

25
Q
Glycogen Catabolism (Glycogenolysis): Formation of free Glucose in the \_\_\_\_
• Liver \_\_\_\_ converts Glucose 6-P into Glucose.
A

liver

glucose 6-phosphatase

26
Q

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 ____ .

A

peripheral tissues (brain)

27
Q

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 ____.
A

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

28
Q

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

A

carbohydrate-rich

29
Q

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 ____.

A

fasting
glucostat
circulation

glucose 6-phosphatase
glycolytic pathway

30
Q

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 ____

A
glycogen phosphorylase
glycogen synthase
glycogen phosphorylase
glycogen synthase
glucose sensor
inactive b form
31
Q

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.

A
protein phosphatase 1
glycogen synthase b
glycogen synthase a
glycogen phosphorylase a
glycogen phosphorylase b
glycogen phosphorylase
glycogen synthase
32
Q

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.

A
adenylate cyclase
protein kinase A
phosphorylase kinase
glycogen phosphorylase b
glycogen phosphorylase a
glycogen synthase a
glycogen synthase b
glycogen synthase
glycogen phosphorylase
33
Q

Overview of glycolysis: two phases: ____ and ____

A

preparatory phase

payoff phase

34
Q

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 ____.

A

pyruvate
ATP
NADH

35
Q

Glycolysis: Conversion of Glucose 6-phosphate to Fructose phosphates

____
____: 2nd priming reaction

A

isomerization

phosphorylation

36
Q

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).

A

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

37
Q

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 ____

A

dehydrogenase
oxidation
payoff reaction

38
Q

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

A

nicotinamide adenine dinucleotide
niacin
NAD+

39
Q

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

A

2nd payoff reaction
substrate level phosphorylation
kinase
2 ATPs

40
Q

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.

A
mutase
enolase
3rd payoff reaction
pyruvate kinase
2 ATPs
41
Q

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 ____.

A

TCA (Krebs) cycle
NADH
ATP

NADH
pyruvate
NAD+

ethanol

42
Q

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.

A
glycolysis
liver
aldolase B
fructose 1-phosphate
fructose 1,6-bisphosphate
43
Q

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.

A
Glc6P
ATP/AMP ratio
citrate
pyruvate kinase
liver
ATP
44
Q

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 ____.

A
PFK-1
activated
inhibited
inhibited
PFK-2
allosterically
PFK-1
45
Q

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 ____.

A

NADPH
ribose 5-P

six
glucose 6-phosphate
CO2

46
Q

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 (____)
A

oxidatively decarboxylated
NADP+
NADPH
CO2

isomerized
nucleotide synthesis pathway
non-oxidative PPP

47
Q

Non-oxidative Phase of the Pentose Phosphate Pathway

Based on reversible reactions:

  • – If there no need for nucleotide biosynthesis:
  • —- ribose 5-P converted into ____
A

glycolytic intermediaries

48
Q

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 ____
A
G6P
4
pentoses
hexoses
NADPH
CO2
49
Q

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 ____
A

oxidative pathway

ribose 5-P synthesis