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BIOCHEMISTRY

(CARBOHYDRATE AND METABOLISM OF


GLUCOSE)

WEEK 2
apt. Baiq Risma Fatmayanti, M.Sc.
Carbohydrate
• Carbohydrate - any of a large group of organic compounds that includes sugars, starch,
and cellulose, containing hydrogen and oxygen in the same ratio as water (2:1) and
used as structural materials and for energy storage within living tissues.
• Function of carbohydrate:
1. Provide energy source – a fuel source when catabolized during cellular respiration.
2. Provide energy storage – plants store energy in a complex carbohydrate form
called starch (amylose) whereas animals store energy in a complex carbohydrate
in their muscle tissues and liver called glycogen.
3. Structural building material – plants build their cell walls of a complex carbohydrate
material called cellulose. Animals such as arthropods build their cytoskeleton of a
complex carbohydrate called chitin. Chitin is also found in fungi.
Carbohydrate
Glucose utilization
Energy
Adipose Stores Glycogen

Glucose
Pentose Phosphate Pathway Glycolysis
or HMS

Ribose-5-phosphate & NADPH Pyruvate & NADH

NADPH: plays a role as an electron donor (hydride ion donor) in NADH: oxidized by the respiratory organ system
reduction reactions in the biosynthesis process to produce ATP
Glycolysis
• Glycolysis is a series of reactions that extract energy from glucose by
splitting it into two three-carbon molecules called pyruvates.
• Glycolysis takes place in the cytosol of a cell, and it can be broken
down into two main phases: the energy-requiring phase and the
energy-releasing phase.
• Glucose is an essential starting material for the glycolysis process.
Glycolysis doesn’t require oxygen (anaerobic).
• Output of glycolysis are 2 pyruvate, 2 ATP, and 2 NADH.
Energy-releasing phase Energy-requiring phase

10
1

9
2

8
3
Glycolysis

7
4

4
5

6
Glycolysis: Energy-requiring phase
• Step 1 - a phosphate group is transferred from ATP to glucose, making glucose-
6-phosphate. Glucose-6-phosphate is more reactive than glucose, and the
addition of the phosphate also traps glucose inside the cell since glucose with a
phosphate can’t readily cross the membrane.
• Step 2 - glucose-6-phosphate is converted into its isomer, fructose-6-phosphate.
• Step 3 - a phosphate group is transferred from ATP to fructose-6-phosphate,
producing fructose-1,6-bisphosphate.
• Step 4 - Fructose-1,6-bisphosphate splits to form two three-carbon sugars:
dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate. They are
isomers of each other, but only one glyceraldehyde-3-phosphate can directly
continue through the next steps of glycolysis.
• Step 5 – DHAP is converted into glyceraldehyde-3-phosphate. The two molecules
exist in equilibrium, but the equilibrium is “pulled” strongly downward, in the
scheme of the diagram above, as glyceraldehyde-3-phosphate is used up.
Glycolysis: Energy-releasing phase
• Step 6 - Two half reactions occur simultaneously: 1) Glyceraldehyde-3-phosphate
(one of the three-carbon sugars formed in the initial phase) is oxidized, and
2) NAD+ is reduced to NADH. The overall reaction is exergonic, releasing energy
that is then used to phosphorylate the molecule, forming 1,3-
bisphosphoglycerate.
• Step 7 - 1,3-bisphosphoglycerate donates one of its phosphate groups to ADP,
making a molecule ATP and turning into 3-phosphoglycerate in the process.
• Step 8 - 3-phosphoglycerate is converted into its isomer, 2-phosphoglycerate.
• Step 9 - 2-phosphoglycerate loses a molecule of water, becoming
phosphoenolpyruvate (PEP). PEP is an unstable molecule, poised to lose its
phosphate group in the final step of glycolysis.
• Step 10 – PEP readily donates its phosphate group to \[\text{ADP}\], making a
second molecule of ATP. As it loses its phosphate, PEP is converted to pyruvate,
the end product of glycolysis.
Pentose phosphate
• Another name for the pentose phosphate pathway is the hexose monophosphate shunt
(HMS).
• This pathway is the major site for the production of:
1. NADPH for anabolism (reductive).
2. Ribose-5-phosphate for nucleotide synthesis.
• Completely oxidizes glucose without Krebs. No ATP is used or made in this pathway.
• Tissue that carries out the pentose phosphate pathway:
1. Erythrocytes produce NADPH which is necessary to maintain glutathione in a
reduced form  maintain the integrity of cell membranes.
2. Liver, mammary glands, testes, adrenal cortex, sites of fatty acid and steroid
synthesis require NADPH. In the liver 20-30% of CO2 produced is produced from
pentose phosphate.
3. Muscle: all glucose 6-phosphate (G6P) catabolism via glycolysis and Krebs cycle.
Pentose phosphate
The different structures between NADH (from glycolysis and Krebs cycle) and
NADPH (from pentose phosphate pathway):

NADH

NADPH
Pentose phosphate

1st oxidative step


Phase 1: oxidative
2nd oxidative step

Phase 2: nonoxidative
including isomerization,
epimerization and
rearrangement
Pentose phosphate
Pentose phosphate
Krebs Cycle
• Krebs cycle = citric acid cycle = tricarboxylic acid cycle (TCA)
• The Krebs cycle pathway is a commonly used pathway for oxidation of fuel molecules such as
carbohydrates, amino acids, and fatty acids. Most of these fuel molecules enter the cycle as an
acetyl Co-A.
• Krebs cycle requires oxygen (aerobic) to change molecules to become an acetyl group or carboxylic
acid group.
• The function of the cycle is to harvest high-energy electrons from fuel molecules from acetyl CoA
and use them to form NADH & FADH2 (high-energy electron carriers).

• TCA occurred at the matrix of mitochondrion.


• Starting material: pyruvate from glycolysis, acetyl Co-A, and oxaloacetate.
• Two turns are needed because glycolysis produces two pyruvic acid molecules when it splits
glucose

• Output: 2 ATP, 6 NADH, 2 FADH2, and 4 CO2 (two cycles)


Krebs Cycle
2 CO2, 2 acetyl Co-A, Decarboxylation
2 NADH oxidative
Transfer electron of NAD+ to NADH
(oxidation reaction)
H O O
H H
C C
NH 2 NH 2

+
N  2 e + H+ N

R R
+
NAD NADH

Proton gradient generates 3


ATP per NADH, & 2 ATP per
FADH2. So for 1 cycle: (9 ATP
from 3 NADH + 2 ATP from 1
FADH2) + 1 ATP from GDP.
Thus, 1 acetate unit generates
the equivalent of 12 ATP
molecules for each cycle.
Total 24 ATP for two cycles.

The Krebs cycle itself actually begins when acetyl-CoA combines with a four-carbon molecule called OAA
(oxaloacetate). This produces citric acid, which has six carbon atoms. This is why the Krebs cycle is also
called the citric acid cycle.
Glycogenesis
• Glycogenesis - glycogen synthesis occurs by adding glucose to the existing
glycogen structure.
• UDP-glucose is required for glycogenesis. Synthesis of UDP-glucose involving
glucose-1-phosphate and UTP mediated by UDP-glucose phosphorylase
enzymes.
• Once the UDP-glucose molecules are formed, they are utilized by the glycogen
synthase enzyme to form a linear chain of alpha D-glucose. An important feature
of this enzyme is that it can only elongate already existing chains of glycogen.
It cannot begin the synthesis of a new chain starting from the first residue. A
primer is always needed by the glycogen synthase enzyme to begin its process.
• Output: glycogen - glycogen is a branched polymer of alpha-glucose. The
glucose molecules are linked together via alpha 1-4 glycosidic linkages in the
linear chains while the residue at the branch points are linked via alpha 1-6
glycosidic linkages.
Glycogenesis
Glycogenesis
• UDP-glucose synthesis
Glycogenesis
• Glycogen synthesis: adds only to the non-reducing ends of glycogen.

Glycogen Synthase
Glycogen

This representation
shows glycogenin on
the reducing end of
a glycogen
molecule.

All of the non-


reducing ends serve
as substrate for
breakdown or
synthesis.
Glycogenesis: branching chain
• The next step in glycogenesis is the process of making branching so that a highly
branched molecule is formed by amylo-alpha(1-4) to alpha(1-6) transglucosidase.
• Steps for branching glycogen chain:
1. The branching enzyme removes a short chain of six to eight glucosyl residues
from the non-reducing end of the linear chain by breaking an alpha 1-4
glycosidic linkage.
2. The branching enzyme inserts this short linear branch at a non-reducing residue
of the chain via an alpha 1-6 glycosidic bond. The first residue at the branch
point is attached via an alpha 1-6 glycosidic bond while the rest of the residues
in the chain have the same alpha 1-4 glycosidic linkages.
3. Once the branch has been formed, both the chains can be further elongated by
the glycogen synthase enzyme.
Glycogenesis: branching chain
Glycogenesis

MW 250000 to > 1000000


Glycogenolysis
Glycogenolysis - the process of breakdown of glycogen to yield glucose residues. The process of
glycogenolysis takes place in the skeletal muscles as well as in the liver.

Glycogenolysis
Glycogenolysis
• Step 1: addition of phosphate at the non-reducing end which is
catalyzed by phosphorylase.
Glycogenolysis
• Step 2: conversion of glucose 1-phosphate to glucose 6-phosphate catalyzed by
phosphoglucomutase. An intermediate glucose 1,6-bisphosphate can be formed.
Summary: Metabolism of Carbohydrates
(Glucose)
GLYCOGEN

Glycogenolysis Glycogensis

GLUCOSE NADPH & Ribose 5-


Pentose phosphate
Glikolysis phosphate

Lactate/Pyruvate & ATP

Krebs cycle

ATP, NADH, FADH2

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