metabolism of...

Metabolism of saccharidesVladimíra Kvasnicová

Glucose transport into cells: facilitated diffusion(protein transporter GLUT – various types)

ERYTROCYTES NERVOUS TISSUE

- insulin-independent transport

The figure is found at http://www.kumc.edu/research/medicine/biochemistry/bioc800/car02fra.htm (Jan 2007)


HEPATOCYTES

- insulin-independent transport

FATTY TISSUE MUSCLES

- insulin-DEPENDENT transport

insulin increases number of glc transporters


The figure was accepted from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley-Liss, Inc., New York, 1997. ISBN 0-471-15451-2

Secondary-active transport of GLC: symport with Na+

- small intestine, kidneys


Glc-6-P !!!

+ NADPH

= hepatocyte

Choose correct statement(s) about glucose transport:

a) glc is transported in blood bound to its transport protein

b) insulin increases number of GLUT-4transporters in plasma membrane

c) secondary active transport of glc into cells is found in a small intestine and the kidneys

d) phosphorylated glucose is not transported through cellular membrane

The figure was accepted from Trends in Biochemical Sciences, reference edition, volume 6, str. 209.Elsevier/North-Holland Biomedical Press, 1981.

1st phase

2nd phase

3rd phase

G

L

Y

C

O

L

Y

S

I

S

The figure has been adopted from: J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2nd edition, Thieme 2005

glucose entering

glycolysis

The figure is found at http://web.indstate.edu/thcme/mwking/glycolysis.html (Jan 2007)

The enzymes you must know


2

2

Products of aerobic glycolysis

Products of anaerobic glycolysis

NADHwas consumed in conversion of

pyruvate to lactate

2,3-BPG shunt

IN ERYTROCYTES:

2,3-BPG ↓↓↓↓ affinity of Hb to O2


• glukagon (repression, inhibition by phosphorylation)

• ↑ ATP / AMP• acetyl-CoA

• insulin (induction)• fructose-1,6-bisphosphate (feed foreward regulation)

pyruvate kinase

• ↑↑↑↑ ATP / AMP• citrate• acidic pH

• ↓ ATP / AMP• fructose-2,6-bisphosphate(↑ if ↑ insulin / glucagon)• insulin (induction)

6-phosphofructo-1-kinase (PFK-1)

main regulatory enzyme

(key enzyme)

• fructose-6-phosphate• insulin (induction)• fructose-1-phosphate(liver)

glucokinase

• glucose-6-phosphatehexokinase

inhibitionactivationregulatory enzyme

Regulation of glycolysis


IRREVERSIBLE REACTION


The glucokinase has higher value of Kmthan hexokinase∼ glucokinase has lower affinity to glucose

(it needs more glucose to reach the reaction velocity of Vmax/2)

Km Km


= substrate level phosphorylation

(ATP formation using energy released from cleavage of an energy rich compound = macroergic compound)



= substrate level phosphorylation

Pi +


Fate of NADH+H+

MALATE-ASPARTATE SHUTTLE

Transport of reducing equivalents to mitochondria

The figure was accepted

from Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley-Liss, Inc.,

New York, 1997. ISBN 0-471-15451-2

GLYCEROL PHOSPHATE SHUTTLE



= transamination

= carboxylation = oxidative decarboxylation

= reduction

If glucose is degradated in a glycolysis

a) 2 pyruvates are formed from 1 glucose

b) 2 ATP are consumed

c) reducing equivalents are transported to mitochondria by a shuttle mechanism

d) 2,3-bisphosphoglycerate can be formed as a side product

Choose correct statement(s) about regulation of glycolysis:

a) regulatory enzymes catalyze irreversible reactions

b) glycolysis is inhibited by insulin

c) glycolysis is inhibited if ATP/ADP is high

d) glucokinase - a regulatory enzyme – has higher affinity to glc than hexokinase

The figure was found at http://www.biochem.arizona.edu/classes/bioc462/462b/graphics/GlycolysisGN

GLehn4Fig14-16.jpg (Dec 2007)

Gluconeogenesis

proceeds as a „reversed glycolysis“

with exception of

3 reactions !

The figure has been adopted from J.Koolman, K.H.Röhm / Color Atlas of Biochemistry, 2nd edition, Thieme 2005

glucose entering

glycolysis

pyruvateentering

gluconeogenesis

Gluconeogenesis

= formation of glucose from

non sugarprecursors

The figure was found at http://www2.mcdaniel.edu/Chemistry/CH3321JPGs/Metabolism/Gluconeogenesis.jpg (Dec 2007)


in MITOCHONDRIA only

Cori cycle

and muscle


Glucose-alanine cycle


= tuk


• insulin (repression)• cortisol, glucagon (induction)

glucose-6-phosphatase

• ↑ AMP / ATP• fructose-2,6-bisphosphate (↑ if ↑insulin / glucagon)• insulin (repression)

• cortisol, glucagon (induction)

fructose-1,6-bisphosphatase

• insulin (repression)• cortisol, glucagon (induction)

phosphoenolpyruvatecarboxykinase

• insulin (repression)• acetyl-Co A• cortisol, glucagon (induction)

pyruvate carboxylase


Regulation of gluconeogenesis


Gluconeogenesis

Gluconeogenesis

a) starts always from pyruvate

b) is catalyzed by the same enzymes as glycolysis

c) participates in a conversion of carbon skeleton of fatty acids (e.g. palmitic acid) to glucose

d) proceeds only in the liver and the kidneys

Choose correct statement(s) about regulation of gluconeogenesis:

a) it is activated by glucagon

b) regulatory enzymes of gluconeogenesis are identical with regulatory enz. of glycolysis

c) gluconeogenesis is activated during starvation

d) pyruvate carboxylase is one of the regulatory enzymes of gluconeogenesis

GLYCOGEN (Glc)n

The figure was found at http://students.ou.edu/R/Ben.A.Rodriguez-1/glycogen.gif (October 2007)

nonreducing end reducing end

OH


Metabolism of glycogen

animation


glycogen glucose

ATP

ADPPi

• glucagon, adrenaline

(phosphorylation)

• insulin (induction)• glucose-6-phosphate

glykogen synthase(glycogen synthesis)

• ↑ ATP / AMP• glucose-6-phosphate• glucose

• glucagon, adrenaline

(phosphorylation)

• ↓ ATP / AMP• Ca2+ (muscle)

glykogenphosphorylase(glycogen degradation)


Regulation of glycogen metabolism

Glycogen

a) is synthesized by glycogen phosphorylase

b) serves as a source of blood glucose during starvation

c) is broken down if insulin/glucagon is high

d) is synthesized from UDP-glucose

The figure is found at http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-3/ch15_pentose-alternatives.jpg (Dec 2006)

Pentose cycle(= Hexose MonoPhosphate Pathway, HMPP)

IRREVERSIBLE

REVERSIBLE(interconversion of

saccharide monophosphates)

The figure is found at http://web.indstate.edu/thcme/mwking/pentose-phosphate-pathway.html (Dec 2006)

The figure is found at http://web.indstate.edu/thcme/mwking/pentose-phosphate-pathway.html (Dec 2006)

intermediates of glycolysis

synthesis of nucleotides

The figure is found at http://www.richmond.edu/~jbell2/14F34.JPG (Dec 2006)

The figure is found at http://courses.cm.utexas.edu/archive/Spring2002/CH339K/Robertus/overheads-3/ch15_pentose-alternatives.jpg (Dec 2006)

Regulation of HMPP

• on the level of substrates availability and products consumption

↑↑↑↑ NADPH / NADP+

reaction using NADP+ are inhibited by lackof the coenzyme

Pentose cycle

a) is a source of NADH+H+

b) includes reactions which are able to transform glucose to 6 CO2

c) is regulated on the level ofglucose-6-phosphate dehydrogenase

d) is interconnected with glycolysis by glc-6-P, fructose-6-P and glyceraldehyde-3-P

Metabolism of fructose in the liver


glycolysis or gluconeogenesis

synthesis of TAG

Fructose

a) can be phosphorylated either to fru-6-Por to fru-1-P

b) can be transformed to body fat

c) in a form of fru-1-P inhibits glucokinase

d) can not be transformed to glucose in the human body

Metabolism of galactose


epimerizationproceeds on the level of

UDP-derivatives


Synthesis of glucuronic acid

Glucose can be transformed to

a) ribose: HMPP participates in the conversion

b) fructose, e.g. glc → glucitol → fructose

c) glucuronic acid: by oxidation of glucose on C1

d) galactose: galactose is 2-epimer of glucose

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