CH 8: carbohydrate metabolism

metabolism

consists of anabolism and catabolism.

anabolism

synthetic pathways. Build complex molecules from simpler ones requiring energy input from ATP and reducing power from NADPH.

catabolism

degradative pathways. Complex molecules are broken down into simpler ones. Releases energy for the body to use. Examples include the breakdown of food during digestion and the conversion of glucose to produce cellular energy through cellular respiration.

step 1 of catabolism in aerobic cell

 major nutrients, protein, carbohydrates, and lipids are digested to their building blocks, amino acids, sugars, and fatty acids respectively

step 2 of catabolism in aerobic cells

 in this stage building blocks are further degraded to form ‘acetly-CoA”

step 3 of catabolism in aerobic cells

Acetyl-CoA is completely oxidized to form CO2 and water through Tri carboxylic Acid cycle and electron transport chain. During the process of oxidation, the energy rich hydrogens are transferred to the carriers like coenzyme NAD and FAD. Significant amount of energy is released when NADH and FADH2 are oxidized during the ‘Electron transport chain’. Portion of this energy is utilized for the synthesis of ATP.

How is the significant amount of free energy generated from the oxidation of NADH in ETC

as the electrons move from NADH to oxygen during ETC which is used to synthesize ATP.

amphibolic pathways

dual-function pathways where the reactions are reversible. each enzyme catalyzes both forward and reverse reactions.

examples of amphibolic pathways

Glycolysis and Gluconeogenesis in liver are the examples of dual-function pathways where one or more irreversible reactions function as highly regulated controlled points.

balance between the anabolism and catabolism

In animals this balance is maintained by the action of hormones(endocrine systems) and nervous system. Hormones are secreted by glands, flow through blood and reach to the target cells. The receptors on the cell surfaces mediate the signals to the intracellular components. The signals through the receptor are mediated through the second messenger molecules which may be Cyclic AMP, cGMP, Ca 2+ ion etc. The regulation by nervous system is mediated by neurons and neurotransmitters.

glycogen metabolism

Synthesis and degradation of glycogen is carefully regulated in order to make sufficient energy available for body’s energy needs.

what three hormones control glycogenesis and glycogenolysis

insulin, glucagon, and epinephrine.

glycogenesis

Synthesis of Glycogen from glucose. When glucose molecules enter cells, they are phosphorylated which prevents their transport out of the cells as well as may facilitate their binding to the active site of an enzyme.

what catalyzes phosphorylation in glycogenesis

hexokinase in the presence of ATP-Mg2+ complex which acts as a co substrate for the enzyme.

reversible conversion of glucose-6- phosphate to glucose-1-phosphate

occurs by enzyme phosphoglucomutase. This enzyme contains phosphoryl group attached to its reactive serine residue. During the reaction first it transfers this phosphoryl group to carbon 1 of Glucose-6-P to form Glucose 1,6-biphosphate. The phosphoryl group from carbon 6 is then transferred to the serine residue of enzyme to form Glucose-1-Phosphate.

Glucose-1-phosphate to UDP-Glucose

This is also a reversible reaction catalyzed by an enzyme UDP-glucose phosphorylase.

What drives the formation of UDP-glucose to completion

deltaGdegree’ is near zero but the reaction is still driven towards completion due to immediate hydrolysis of pyrophosphate with large loss of free energy (G’ = -8kcal/mole).

The formation of glycogen from UDP-glucose requires what two enzymes

glycogen synthase and amylo-alpha (1,4 —> 1,6)-glucosyl transferase.

glycogen synthase 

This enzyme catalyzes the transfer of glucosyl group of UDP-glucose to the nonreducing ends of glycogen.

amylo-alpha (1,4 —> 1,6)-glucosyl transferase

this enzyme creates the alpha (1,6) linkage for branches in the molecules.

what is believed to initiate glycogen syntheses

the transfer of glucose from UDP-glucose to a specific tryosine 194 residue in a “primer protein” called glycogenin.

what two enzymes are required for glycogen degradation

glycogen phosphorylase and amylo-alpha (1,6)-glucosidase (branching enzyme).

glycogen phosphorylase

this enzyme removes glucose  residues from the nonreducing end of the outer branches of glycogen.

amylo-alpha (1,6)-glucosidase (branching enzyme)

This enzyme hydrolyzes the alpha (1,6) glycosidic bonds at branch points. Glycogen phosphorylase utilizes inorganic phosphate and cleaves terminal glucose residue by breaking alpha (1,4) linkage to yield Glucose-1-phosphate. At branching point this enzyme stops and the debranching enzyme starts breaking alpha (1,6) linkage.

regulation of glycogen metabolism

regulated by complex mechanism involving, insulin, glucagon and epinephrine. Actions of these hormones are mediated by second messenger molecule known as ‘Cyclic AMP(cAMP)’.

glycolysis 

considered one of the most ancient biochemical
pathways. It is also known to as ‘Embden-Meyerhof-Parnas’
pathway. During glycolysis six carbon glucose is converted to three
carbon pyruvate molecules.

when pyruvate is made in glycolysis anaerobicly what does it produce

lactic acid, acetic acid, anf ethanol.

when pyruvate is made in glycolysis aerobicly what does it produce

complete oxidation CO2 and H2O.

first stage of glycolysis

Conversion of one glucose molecule to two Glyceraldehyde- 3-phosphate molecules utilizing two ATP molecules.

second stage of glycolysis

Conversion of two Glyceraldehyde-3-phosphate molecule to two pyruvate molecules yielding four molecules of ATPs and two NADH molecules.

Net yield of ATP is still two ATP molecules since two ATP molecules are utilized in first stage.

stage one of glycolysis, pt. 1

Glycolysis begins with Glucose-6-Phosphate which is
reversibly converted to Fructose-6-Phosphate by an enzyme
Phosphoglucose isomerase.

stage one of glycolysis, pt. 2

Phosphofructokinase-1(PFK-1) then catalyzes phosphorylation of Fructose-6-phoshate to Fructose-1,6 biphosphate utilizing ATP as phosphate donor. Thus the reaction proceeds with large loss of energy and is irreversible. Once this reaction takes place, the cell is committed to degrade glucose to pyruvate. The
activity of this enzyme is inhibited by high concentration of ATP and citrate while it is accelerated by high concentration of AMP.

stage one of glycolysis, pt. 3

Stage 1 glycolytic reactions end by conversion of six carbon Fructose-1,6-biphosphate to three carbon Glyceraldehyde-3- phosphate and Dihydroxyacetone phosphate. The enzyme catalyzing this reaction is ‘Aldolase’. Dihydroxyacetone phosphate is then reversibly converted to Glyceraldehyde-3-Phosphate by an enzyme Triose Phosphate isomerase. Thus at the end, one molecule of glucose is converted to two molecules of Glyceraldehyde-3- P.

stage two of glycolysis, pt. 1

 Glyceraldehyde-3-P undergoes oxidation and
phosphorylation simultaneously to form Glycerate-1,3-biphosphate.
The reaction is catalyzed by Glyceraldehyde-3-phosphate
dehydrogenase which is a tetramer composed of four identical
subunits containing one site for G-3-P and one for NAD.

stage two of glycolysis, pt. 2

in this step Glycerate-1,3-biphosphate donates one
phosphate to ADP to generate one ATP and Glycerate-3-Phosphate.
The reaction is catalyzed by an enzyme Phosphoglycerate kinase.
This is an example of substrate level phosphorylation where ATP is
synthesized by transfer of phosphoryl group from substrate.

stage two of glycolysis, pt. 3

Since Glycerate-3-P has low phosphoryl group transfer potential (-3kcal/mole) it can not be used for the formation of ATP. Cell converts Glycerate-3-P to Phophoenolpyruvate with very high phosphate group transfer potential (-14kcal/mole). In first step Glycerate-3-P is converted to Glycerate-2-P by Phosphoglycerate mutase with Glycerate-2,3-bisphosphate as an intermediate.

stage two of glycolysis, pt. 4

 Enzyme ‘Enolase’ catalyzes the dehydration of Glycerate- 2-Phosphate to Phosphoenolpyruvate(PEP).

stage two of glycolysis, pt. 5

 In the final step of glycolysis, enzyme ‘Pyruvate kinase’ catalyzes the transfer of a phosphoryl group from PEP to ADP to form ATP and pyruvate. Thus end of glycolysis converts one molecule of Glucose to two molecules pyruvate and produces two molecules of ATP. Because of exceptional high energy of PEP, this reaction is irreversible.

fate of pyruvate, aerobic conditions

 Under aerobic conditions pyruvate is converted to Acetyl-CoA. Acetyl-CoA is then channeled through citric acid cycle to form CO2. During series of oxidation-reduction reactions hydrogen is transferred via NAD/FAD to the electron transport chain to form ATPs.

fate of pyruvate, anaerobic conditions

Under anaerobic conditions pyruvate is metabolized by living cells in many different ways. For example muscle cells and some bacteria(Lactobacillus sp.) convert puruvate to lactic acid with formation of NAD which is utilized during the glycolysis. Some organisms form more than one type of organic acids along with lactic acid, for example, propionic acid and butyrate.

Yeast and several bacteria

 ferment sugar to form alcohol. In yeast pyruvate is decarboxylated to form acetaldehyde, which is reduced by NADH to form ethanol. Certain bacteria such as Clostridiun acetobutylicum, produces butanol instead of ethanol.

Hexokinase, PFK-1, and Pyruvate kinase

 The rate of glycolytic reactions are regulated by allosteric regulation of the enzymes.

what hormones also control gylcolysis

Insulin and glucagon primarily control glycolysis, promoting or inhibiting glucose metabolism based on the body's energy needs.

what does glucagon do in glycolysis

inhibits the synthesis of fructose-2,6-biphosphate

what does insulin do in glycolysis

 romotes synthesis of fructose-2,6-biphosphate.

gluconeogenesis 

it is the pathway through which glucose is formed from non carbohydrate precursors mainly in liver cells. The organic precursors include: lactate, pyruvate, glycerol, and certain alpha-keto acids. Gluconeogenesis is the means by which liver cells provide glucose to the body cells when glycogen is depleted.

the reactions of gluconeogenesis

Most of the gluconeogenesis reactions are reverse of glycolysis reactions. The irreversible glycolytic reactions are bypassed by energetically more favorable reactions. These unique reactions are synthesis of PEP.

synthesis of PEP 

Two enzymes are involved:pyruvate
carboxylase and PEP carboxykinase. Pyruvate carboxylase converts
pyruvate to oxaloacetate(OAA) with consumption of ATP. OAA is
decarboxylated and phosphorylated by PEP carboxykinase in a
reaction driven by the hydrolysis of Guanosine triphosphate (GTP).

Fructose-1,6-biphosphate to Fructose-6-phosphate

This reaction is catalyzed by an allosteric enzyme Fructose- 1,6-biphosphatase. Its activity is stimulated by citrate and inhibited by AMP and Fructose-2,6-biphosphate.

glucose-6-phosphate to glucose

The enzyme Glucose-6-phosphatase only found in liver and kidney, catalyzes irreversible conversion of glucose-6-phosphate to glucose and Pi. Glucose thus formed is subsequently released in blood. Gluconeogenesis is energy consuming process and utilizes six molecules of ATP.

gluconeogenesis regulation

The four key enzymes in gluconeogenesis: Pyruvate carboxylase, PEP carboxykinase, Fructose-1,6-biphosphatase and Glucose-6-phosphatase are regulated allosterically. Fructose-1,6-biphosphatase is stimulated by ATP and inhibited by AMP and fructose-2,6-biphosphate. Pyruvate carboxylase is activated by Acetyl-coA. Since the synthesis of the allosteric modulators are affected by hormones, they also regulate the rate of reactions of gluconeogenesis.