Biochemistry- Saccharide Metabolism

Front 1

Oligosaccarides:

Back 1

1. Sucrose
2. Lactose
3. Maltose

Front 2

Polysaccarides:

Back 2

1. Cellulose
2. Starch
3. Glycogen

Front 3

Heteroglycosides:

Back 3

1. Glycoproteins
2. Proteoglycans
3. GAGs
4. Glycolipids

Front 4

Saccharides:

Back 4

1. Polyhydroxyketones
2. Polyhydroxyaldehydes

Front 5

Chiral carbon:

Back 5

A carbon which as for different substituents connected to it.

Front 6

What is an isomer?

Back 6

Compounds that have same chemical formula but different structure

Front 7

Formula for how many chiral carbons:

Back 7

2n (where n=nr of C)

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Epimers:

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An carbohydrate isomer that differ in configuration around only one specific carbon (except the carbonyl carbon).

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Examples of isomers:

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Fructose, Glucose, Mannose and Galactose with formula: C6H12O6

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Enatiomers:

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A special type of isomerism found in pair structures that are mirror images of each other. D- and L- sugar. (Most human sugars are D-: OH- group on the asymetrical carbon farthest from the carbonyl carbon is on the right

Front 11

Classification of aldoses:
1. Trioses
2. Tetroses
3. Pentoses
4. Hexoses

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1. Glyceraldehyde
2. Erythrose
3. Ribose
4. Glucose

Front 12

Classification of ketoses:
1. Trioses
2. Tetroses
3. Pentoses
4. Hexoses

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1. Dihdroxyacetone
2. Erythrulose
3. Ribulose
4. Fructose

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Pyranoses:

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Aldohexoses (Glucose)

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Furanoses:

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Fructose and Ribose

Front 15

Anomeric carbon:

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Former carbonyl carbon that reacts with an alcohol group on the same sugar during cyclysation creating alpha and beta configurations

Front 16

Trans vs. cis configuration:

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1. Alpha configuration in Haworth projection formula the OH group on the anomeric carbon is trans to the CH2OH (6th carbon in case of hexoses)
2. In beta- configuration it is on the same side (up)

Front 17

Epimers of monosaccharides:

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1. Glucose- Mannose (2- epimer)
2. Glucose- Galactose (4- epimer)

Front 18

Where can galactose and mannose be found?

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1. Galactose is found in lactose (milk sugar)
2. Galactose and mannose are found in heteroglycosides

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Reducing sugar:

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If the hydroxyl group on the anomeric carbon of cyclized sugar is not linked to another compound by a glycosidic bond it can the ring can open and the OH can oxidize acting as a reducing agent or be reduced

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Sugar alcohols are formed:

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By reduction of the carbonyl group

Front 21

Examples of derivatives of monosaccharides:

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1. Glucose--> glucitol (sorbitol)
2. Mannose--> mannitol
3. Galactose---> galactitol

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Oxidation of monosaccharide
1. Produced:
2. Examples:

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1. Acids
2. Aldaric acid (C1 and C6 is oxidized)
Aldonic acid (C1 oxidation)
Alduronic acid (C6 oxidation)

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Esterification of monosaccharides:

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1. With phosphoric acid in intermediates of metabolism
2. With sulfuric acid in proteoglycans

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O- glycosidic bond is formed:

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Between oligo and polysaccharides and connection to proteins

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N- glycosidic bonds is formed:

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In nucleic acids and in connection to proteins

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Disaccharides:
1. Examples
2. Do they have reducing properties:

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1.
- Lactose: Beta- D- Galactopyranosyl(1-4)- D- Glucopyranose (milk)
- Maltose: alpha- D glucopyranosyl (1-4)- D- glucopyranose (beer)
- Sucrose: alpha- D- Glucopyranosyl (1-2)- B- D- Fructofuranoside
2. Only the free anomeric hydroxyl group has reducing properties

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Homopolysaccharides:

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1. Starch
2. Glycogen
3. Cellulose
4. Inuline

Front 28

Heteropolysaccharides:

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1. Glycoproteins
2. Proteoglycans

Front 29

Storage saccharides:

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1. Starch
2. Glycogen
3. Inuline

Front 30

Structural saccharides:

Back 30

1. Cellulose
2. Proteoglycans

Front 31

Starch:

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1. Amylose, amylopectine
2.
α (1-4) glycosidic bonds
α (1-6) glycosidic bonds

Front 32

Glycogen:

Back 32

Glucose bond by α- 1,4 and α-1,6 linkages

Front 33

Cellulose:

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β- 1,4 linkages between glucose

Front 34

Proteoglycans:

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Core protein and GAGs

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Glycoprotein:

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Proteins containing oligosaccharides covalently attached to the peptide side chains

Front 36

Blood glucose levels:

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3.3- 6,1 mmol/L

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Maintaining glycemia:

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1. Brain and erythrocytes need constant supply of glucose
2. Glucogenolysis form 4- 24hours after meal
3. From Gluconeogenesis from 4h- days....

Front 38

2 ways for glucose to enter cells:

Back 38

1. By secondary active transport: Simport with Na+ (SGLT 1,3)
- SGLT: sodium glucose transporters
- Located in intestinal epithelial cells and tubular kidney cells
- Glucose moves my facilitated transporters AGAINST concentration gradient
2. By facilitated diffusion (GLUT 1-7)
- GLUT: glucose transport protein
- Insulin increases number of GLUT- 4 transporters in plasma membrane

Front 39

GLUT transporters location (Transport down the concentration gradient):

Back 39

1. GLUT 1: Erythrocytes, blood- brain barrier, INDEPENDENT on insulin
2. GLUT 2: Liver, kidney, panceratic β- cells, INDEPENDENT on insulin
3. GLUT 3: Brain (neurons)
4. GLUT 4: Adipose tissue, skeletal muscle, heart muscle. Is a insulin- SENSETIVE transporter. Nr. of GLUT 4 increases in the presence of insulin

Front 40

Glucose inside cells:

Back 40

1. To keep glucose inside the cell it is phosphorylated.
2. Catalyzed by hexokinase and glucokinase.
3. Glucose is osmotically active and can not exist as glucose inside cell and must either enter glycolysis or Gluconeogonesis (Glycogen is not osmotically active)

Front 41

Km of GLUT 4:

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Km= 12 mmol/L: Function after meals when there is hyperglycemia

Front 42

Km of GLUT 3:

Back 42

Km= 1-2 mmol/L: able to transport from blood to neurons even in hypoglycemia

Front 43

Hexokinase:

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1. Phosphorylates glucose, present in most tissues.
2. Has a low Km= high affinity to glucose and needs a low concentration to reach half of Vmax
3. Is inhibited by glucose- 6- phosphate
4. Serves as a glucose sensor in the neurons of the hypothalamus playing a key role in the adrenergic- response to hypoglycemia.

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Glucokinase:

Back 44

1. Phosphorylates glucose in parachymal cells of the liver and β-cells of the pancreas
2. Glucokinase has a high Km (low affinity to glucose and needs a high concentration to reach half of Vmax) and a high Vmax.
3. In β- cells glucokinase functions as the glucose sensor, determining the threshold for insulin secretion.

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What can the cell do with glucose?

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1. Glycolysis---> FAT or TCA cycle
2. Glycogenesis
3. Pentose phosphate pathway

Front 46

Pyruvate dehydrogenase:

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Enzyme that converts pyruvate into acetyl- CoA. Require oxygen to function

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Glycolysis consists of 3 main phases:

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1st phase: Energy investment. Glucose--> fructose 1,6 bisphosphate
2nd phase: Cleavage of 6 carbon sugar to two 3 carbon sugars. Fructose 1,6. bisphosphate--> 2 glyceraldehyde 3-phosphate
3rd phase: Energy generation. 2 glyceraldeyde 3- phosphate---> 2 Pyruvate

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Glycolysis pathway:

Back 48

1. Glucose--> Glc- 6- P (Hexokinase/glucokinase)
2. Glc- 6- P---> Fructose- 6-P (Phosphoglucose isomerase)
3. Fructose-6- P---> Fructose 1,6- bisphosphate (Phosphofructokinase- 1)
4. Fructose 1,6- bisphosphate is hydrolysed---> Glyceraldehyde- 3- phosphate + Dihydroxyacetone phosphate (Aldolase)
5. Dihydroxyacetone---> Glyceraldehyde 6- phosphate (Triose phosphate isomerase)
6. Glyceraldehyde 3- phosphate---> 1,3- Bisphosphoglycerate (Glyceraldehyde 3- phosphate dehydrogenase)
7. 1,3- Bisphosphoglycerate---> 3- phosphoglycerate (Phosphoglycerate kinase)
8. -----> 2- Phosphoglycerate (Phosphoglycerate mutase)
9. ----> Phosphoenolpyruvate/ PEP (Enolase)
10. --->Pyruvate (Pyruvate kinase)

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Energy gain by glycolysis:

Back 49

2 ATP per Glucose molecule

Front 50

2,3- BPG shunt:

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1. 1,3- Bisphosphiglycerate---> 2,3- BPG (2,3- BPG mutase)
3. 2,3- BPG---> 3- phosphoglycerate (2,3- BPG phosphatase)

Front 51

Regulation of glycolysis:

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1. Glucokinase: Activated by insulin and fructose-1- phosphate (liver). Inhibited by Fructose- 6- phosphate
2. Phosphofrukto kinase-1: Activated by low ATP/AMP ratio, fructose-2,6- bisphosphate (if high insulin/ glucagon ratio) and insulin. Inhibited by high ATP/AMP ratio, citrate and acidic pH (MAIN REGULATORY STEP!!)
3. Pyruvate kinase: Activated by insulin, fructose- 1,6- bisphosphate (feed forward). Inhibited by glucagon, acetyl- CoA and high ATP/AMP ratio.

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Irreversible reactions of glycolysis:

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1. Glucose--> glucose- 6- P
2. Fructose- 6- P---> Fructose-1,6- bisphosphate
3. PEP---> Pyruvate

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Substrate level phosphorylation steps in glycolysis (producing 4 ATP in total/ glucose):

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1. 1,3- Bisphosphoglycerate---> 3- phosphoglycerate
2. PEP---> Pyruvate

Front 54

2 ways of transporting reducing equivalents to mitochondria:

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1. Malate- aspartate shuttle:H+ from NADH is transported into the cell with Malate (1 middle man, higher energy yeld)
2. Glycerol- phosphate shuttle: NADH+ transfers H+ to Glycerol-3- phosphate which transfers H+ and reduced FAD to FADH2

Front 55

Possibilities of Pyruvate:

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1. Gluconeogenesis---> Glucose
2. Transamination---> Alanine
3. Carboxylation---> Oxaloacetate
4. Oxydative decarboxylation---> Acetyl CoA
5. Reduction: Lactate

Front 56

Gluconeogenesis
1. What?
2. Precursors:
3. Location:
4. Activation:
5. Inhibition:

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1. Synthesis pathway of glucose from various precursors
2. Aminoacids, Lactate, and Glycerol
3. 90% in liver, 10% in tubular cells of kidneys
4. Cortisol, glucagon and epinephrine
5. Insulin

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Gluconeogenesis pathway from Glycerol as a precursor:

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1. Glycerol---> glycerol-3- phosphate
2. Glycerol-3- phosphte---> Dihydroxyacetone phosphate
3. Dihydroxyacetone phosphate----> Fructose-1,6- phosphate---->----->----> Glucose

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Gluconeogenesis pathway from Pyruvate (from Alanine, other AAs or Lactate):

Back 58

1. Pyruvate---> (Pyruvate carboxylase, in mitochondria) require biotin
2. Oxaloacetate, leave mitochondria (PEP carboxy kinase, GTP dependent)--->
3. Phosphoenolpyruvate--->
4. ---->----->----->-----> Glyceraldehyde- 3- phosphate----->
5.Fructose 1,6- bisphosphate---> (Fructose-1,6- Bisphosphatase)
6. Fructose-6-P ----> (Phosphoglyco isomerase)
7. Glucose- 6-P---> (Glucose- 6- phosphatase)
6. Glucose

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The Cori Cycle:

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1. Glucose in liver is transported to muscles where it indergoes glucolysis---> 2 Pyruvate producing net 2 ATP
2. 2 Pyruvate is converted to 2 Lactat which is transported back to liver
3. In liver 2 Lactate is concerted to 2 Pyruvate which undergoes gluconeogenesis consuming 6 ATPs and produce one Glucose

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Subcellular location of gluconeogenesis:

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Mitochondria, cytoplasm and ER

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Which enzyme catalyzes conversion from Lactate to Pyruvate?

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Lactate dehydrogenase

Front 62

Hormones influencing all 3 regulatory enzymes of gluconeogenesis:

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1. Activation: Cortisol, glucagon, catecholamines
2. Inhibition: insulin

Front 63

Regulation of pyruvate carboxylase (regulatory enzyme of Gluconeogenesis):

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Activation: acetyl- CoA from beta- oxidation of FA (source of ATP)

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Regulation of Fructose- 1,6- Bisphosphatase (regulatory enzyme of Gluconeogonesis):

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Activation: Citrate, starvation
Inhibition: AMP, Fructose-2,6- Bisphosphate (if high insulin/ glucagon ratio)

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Stoichiometry of Gluconeogenesis:

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Cleavage of 6 high energy phosphate bonds and oxidation of 2 NADH with the formation of 1 glucose molecule

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Glycogen metabolism:
1. How much glycogen can the body store?
2. What is the purpose of liver glycogen?
3. What is the purpose of muscle glycogen?
4. Structure of glycogen?

Back 66

1. 450g
2. Serve as glucose reserve for the maintenance of glycemia
3. Serve as energy for muscle contraction
4. Homopolymer of glucose linked by alpa.1-->4 bonds. Every 12 glucose is connected to a glucose branch with alpha- 1-6 bonds.

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Glycogenesis:

Back 67

1. Glucose---> Glc- P (Glucokinase) in hepatic cells.
2. Glc-6-P--->Glc-1-P (Phosphoglucomutase)
3. Glc- 1-P + UTP---> UDP- glucose "activated glucose" (Glc-1-P uridyltransferase)
4. UDP- glucose---> Glc is transferred to a glycogen primer or Glycogenin protein (glycogen synthase).
5. UDP is released-->+ ATP---> UTP+ ADP
6. Glycogen synthase elongate the chain by adding Glc to the nonreducing end of glycogen.
7. Amylo-(1,4.1,6)- transglycosylase branching enzyme creates alpa- 1-6 bonds and add a branch to every 12th glucose.
8. Glycogen synthase continues to add Glc in alpa-1-4 bonds on the branch

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Glycogen synthase regulation (regulatory enzyme of glycogen synthesis):

Back 68

1. Glycogen synthase is activated in nonphosphorylated form and inactive in phosphorylated form.
2. In muscle:
- Insulin dephosphorylates (activates)
- Adrenalin phosphorylates (inactivates)
In liver:
- Glucose activates
- Glucagon phosphorylates (inactivates)

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Glycogenolysis (glycogen degradation:

Back 69

1. Glycogen phosphorylase lyses the 1-->4 bonds freeing Glc-1-P
2. Glc-1-P---> Glc-6-P (phosphoglucomutase)
3. In liver and kidneys: Glc-6-P---> Glc (Glc-6- phosphatase)
4. Debranching enzymes cleaves 1-6 bonds

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Regulation of glycogen phosphorylase (regulatory enzyme of Glycogenolysis):

Back 70

1. Phosphorylated (active), dephosphorylated (inactiive)
2. Phosphorylase kinase phosphorylase glycogen phosphorylase.
3. Glucagon and epinephrine activates the enzyme, insulin inhibits it.
4. Allosteric effectors:
- Activation: AMP, Ca2+ (muscle)
- Inhibition: ATP, Glc-6-P, Free Glc

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AABB

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professional organization that
accredits and provides
technical guidance to blood banks.

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Oxidative phase of pentose cycle: (Irreversible)

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1. Glc- 6- phosphate---> 6- phosphogluconolacetone (Glc-6-P dehyndrogenase) NADPH+ H+ is released
2. 6- phosphogluconolactone is cleaved by hydration--> 6- phosphogluconate (Gluconolactonase)
3. 6- phosphogluconate is oxidized and decarboxylated--> Ribulose- 5- phosphate (6- phosphogluconate dehydrogenase) releasing NADPH+H+
4. Ribulose- 5- phosphate---> Ribose- 5- P (Ribose isomerase)

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Second phase of pentose cycle:

Back 73

1. Transketolase and transaldolase transfers C2 and C3 units forming intermediates of glycolysis
2. Producing fructose- 6- phosphate and glyceraldehyde-3- phosphate.
3. 3 Rib- 5- P---> 2 Fru- 6- P + Glyceraldehyde-3-P
4. This part is reversible and can be used to convert hexose phosphates into pentose phosphates which can be used in nucleotide synthesis.

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Regulation of pentose cycle:

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Glucose- 6- phosphate dehydrogenase is the main regulatory step and is regulated by NADPH/ NADP+ ratio. (Inhibited by NADPH)

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Metabolism of fructose in the liver:

Back 75

1. Fructose---> (Fructokinase)
2. Fructose-1-phosphate---->(Fructose-1-P aldolase)
3. Glyceraldehyde/ DHAP--->
.4 Glyceraldehyde can be used in synthesis of TAG or be converted to glyceraldehyde- 3-P and enter glycolysis or gluconeogenesis

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Metabolism of Galactose:

Back 76

Galactose----> Glucose- 6-P by changing UDP- Glucose to UDP- Galactose

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CHEMOTACTIC

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movement of cells in the direction
of the antigenic stimulus