PDH Complex; Citric Acid Cycle; Glyoxylate Cycle

PDH complex catalyzes how many reactions

5

a derivative of lipoic acid is linked to the side chain of a lysine residue by an amide linkage. This has an active disulfide bond which will serve as the oxidant of the hydroxyethyl to become acetyl

lipoamide

Reaction 2 is catalyzed by E1 in which forms

acetyl-dihydrolipoamide-E2

___ catalyzes the transesterification reaction in which the acetyl group is transferred to CoA. The Acetyl CoA is removed leaving the dihydrolipoamide of this enzyme

E2

Rxn 4 is catalyzed by ___ which involved the reoxidation of dihydrolipoamide and formation of Acetyl CoA

Dihydrolipoamide dehydrogenase (E3)

Reaction 5 is the reoxidation of ____ with ____

E3; FAD

the ___ funnels the electrons to ___ , yielding ____.

FAD; NAD+ NADH

The length of lipoyllysyl arm (lipoic acid and lysine) is ____ which is deep and long enough allowing it to swing from one active site to another

14 Angstrom

Reaction 2 is the isomerization of citrate to ____ by _____. It is accomplished by a dehydration step followed by a hydration step.

isocitrate; aconitase

Reaction 4 is the oxidative decarboxylation of isocitrate to ___ by _____. This reaction produces the first CO2 and NADH

a-ketoglutarate ; isocitrate dehydrogenase

Reaction 5 is an oxidative decarboxylation reaction catalyzed by ____ forming ____ . It catalyzed the formation of 2nd CO2 and NADH.

α-KETOGLUTARATE DEHYDROGENASE complex; Succinyl CoA

reaction 5 is the cleavage of the thioester bond of succinyl CoA by ____ which is coupled to the phosphorylation of a purine NTP, usually GDP forming a 4C compound ____.

Succinyl CoA synthetase ; succinate

The last 3 reactions of Citric acid cycle is for the resynthesis of ____ from ____.

oxaloacetate; succinate

Reaction 6 of CAC is the oxidation of succinate to _____ by _____. It produces the FADH2 used in ETC.

fumarate; succinate dehydrogenase

Reaction 7 is catalyzed by ___ which catalyzes stereospecific transaddition of H+ and OH- forming ____.

fumarase; L-Malate

The need for energy regulates the citric acid cycle capacity at the ___ level and by the 3 rate controlling ___ enzymes of the cycle.

PDH complex; citrate synthase; isocitrate dehydrogenase, and a-ketoglutarate dehydrogenase

___ ATPs are produced by one glucose molecule that enters glycolysis, pyruvate dehydrogenase complex, CAC and oxidative phosphorylation assuming NADH and FADH2 are processed through aerobic metabolism.

32

In contrast to when the pyruvate is produced anaerobically, only ___ ATP are produced.

2

When pyruvate is processed through the pyruvate dehydrogenase complex, that pathway is irreversible that commits the carbon of acetyl CoA to two fates:

1. Complete oxidation to CO2 through CAC, ETC, and
2. oxidative phosphorylation
Used as a raw material for the synthesis of lipids.

Pyruvate dehydrogenase complex is inhibited by ____, _____ and ____

NADH; acetyl-CoA ; and covalent modification

In PDH complex, acetyl CoA inhibits

dihydolipoyl transacetylase (E2)

In PDH complex, NADH inhibits

dihydrolipoyl dehydrogenase (E3)

The key means of regulation of the complex in eukaryotes

Covalent Modification

Phosphorylation of the pyruvate dehydrogenase (E1) by a specific _____ switches off the activity of the complex. Deactivation is reversed by a specific______.

kinase; phosphatase

If the enzyme that deactivates it is kinase (phosphorylates the enzyme), the specific name/substrate of the enzyme is ____

pyruvate dehydrogenase kinase

When blood glucose is low and glucagon is released, pyruvate dehydrogenase complex is deactivated. ____ is activated.

Phosphatase

When blood glucose is high and insulin is released, pyruvate dehydrogenase complex is activated. _____ is activated.

kinase

At ____ , pyruvate dehydrogenase is switched off by the kinase when the energy charge is high

rest

During ____, ADP and pyruvate activates PDH by deactivating the kinase and the energy charge is low

exercise

This key control point enzyme is stimulated by oxaloacetate and acetyl CoA and inhibited by citrate

citrate synthase

The control on this enzyme is similar to that of the PDH complex. This is inhibited by succinyl Co-A and NADH as well as by high energy charge

a-Ketoglutarate Dehydrogenase

Ractions that use and therefore drain CAC intermediates

Cataplerotic reaction

One cataplerotic reaction is ___ which utilizes oxaloacetate. When glucose is much needed, oxaloacetate can be removed from CAC and converted to _____ by PEPCK.

gluconeogenesis; phosphoenolpyruvate

____ biosynthesis on the other hand, uses α‐ketoglutarate and oxaloacetate as starting materials

Amino Acid

___ biosynthesis is synthesized by reductive amination of alpha-ketoglutarate by ______.

Glutamate; glutamate dehydrogenase

__ biosynthesis is synthesized by reductive amination of oxaloacetate.

aspartate

Oxaloacetate is formed by carboxylation of pyruvate by (1). In the regulation of gluconeogenesis, (1) is activated by acetyl CoA; this enzyme is only active when the concentration of acetyl CoA is (2). It senses the flux of the cycle through the [acetyl CoA].

pyruvate carboxylase; high

When the energy is ___, oxaloacetate is converted to glucose

high

This cycle enables plants and some bacteria to grow on acetate

Glyoxylate Cycle

___ would only appear when the plant is germinating until such time that the plant can synthesize sugar during photosynthesis.

Glyoxysome

the most common disease from citric acid cycle which is linked to mutations of a-ketoglutarate dehydrogenase, succinate dehydrogenase, fumarase, and succinyl-CoA synthetase

Encephalophaties

Central metabolic hub wherein the energy stored in carbon fuels are harnessed and converted into a reduced coefficient

Citric Acid Cycle

Since pyruvate cannot participate directly in CAC, it has to be converted first to

Acetyl CoA

The link between the glycolysis and Citric Acid Cycle

Pyruvate Dehydrogenase Complex

Other carbon fuels from ___ and ___ can also enter the citric acid Cycle

Amino acid and fatty acid

Electrons released from Citric Acid Cycle

Reduced coefficients NADH and FADH2

It is the oxidative BREAKDOWN of nutrients

Catabolism

The reductive SYNTHESIS of metabolites/biomolecules

Anabolism

The citric acid cycle is ___; that is, it plays a role in both catabolism and anabolism. It is the central metabolic pathway

amphibolic

The citric acid cycle is a multistep catalytic process (8 reactions) that converts acetyl groups derived from carbohydrates, fatty acids, and amino acids to

CO2, NADH, FADH2, and GTP

The pyruvate released from the glycolysis is converted to Acetyl CoA by another complex enzyme called the

pyruvate dehydrogenase complex

The reactions of TCA takes place

inside the mitochondria (matrix of mitochondria)

In CAC, 2C Acetyl CoA condenses with 4C oxaloacetate forming a 6C compound that undergoes two consecutive ____.

oxidative decarboxylation;

The dehydrogenases involved in two consecutive oxidative decarboxylation require ___ which is reduced to ___

NAD to NADH

After the two consecutive oxidative decarboxylation, there is a generation of 4C compound which is used to resynthesize

oxaloacetate

Citric acid cycle is the main metabolic hub of an organism. Carbon fuels have to enter the cycle that has to be converted to Acetyl CoA and produce ___ pairs of electrons. ___ of which is transferred to ___ and ___ to FADH2

4; 3; 1

In the conversion of pyruvate to Acetyl CoA, the process would remove ___ carbon from pyruvate as ___ and release a pair of electrons which would be received by ___ to become ____.

1; CO2; NAD+ to NADH

It is a large, highly integrated complex of three distinct enzymes. It is a homologous complex with a mass ranging from 4 to 10 million daltons

PDH

The three enzyme in PDH complex

Pyruvate dehydrogenase component with TPP (Thiamine Pyrophosphate); Dihydrolipoyl transacetylase; Dihydrolipoyl dehydrogenase

The core of the PDH complex enzyme is ___ which is the enzyme __. It has a lipoic acid that is bound to a lysine residue. It transfers acetyl groups to CoA.

dihydrolipoyl transacetylase; 2

This enzyme in PDH complex functions for the oxidative decarboxylation of pyruvate. The prosthetic group of this enzyme is ___

enzyme 1 pyruvate dehydrogenase component; thiamine pyrophosphate

This enzyme in PDH complex functions for the regeneration of the oxidized form of lipoamide.

Enzyme 3; dihydrolipoyl dehydrogenase

Reaction 1 is catalyzed by E1 where ___, decarboxylates pyruvate with the formation of a __

TPP-requiring enzyme; hydroxyethyl-TPP intermediate

Which enzyme reoxidizes back the dihydrolipoamide

Dihydrolipoamide dehydrogenase

Reaction 1 of CAC is the formation of ______ from _____ and _______ by the enzyme ______. This is a series of aldol condensation and hydrolysis.

citrate; acetyl coa and oxaloacetate; citrate synthase

In reaction 1, there is a formation of ____ intermediate which is considered a high energy compound due to its ____ which is actually the energy source for the reaction

Citryl CoA; Thioester bond

Aconitase is an ____ protein.

iron-sulfur

Reaction 8 is catalyzed by ___ which involves the oxidation of malate to form ____. This reaction also produces the 3rd NADH.

malate dehydrogenase; oxaloacetate

Each acetyl-CoA that goes into the cycle would produce 4 pairs of electrons. 3 of which are for ____ producing NADH and 1 for _____ for producing FADH2

isocitrate, malate and alpha ketoglutarate dehydrogenase; sucinnate dehydrogenase

Phosphorylation which inhibits the activity of the enzyme/complex is activated when the phosphate of the phosphorylated enzyme is removed by a specific phosphatase _____

pyruvate dehydrogenase phosphatase

This key control point enzyme is stimulated by ADP and NAD+ while ATP and NADH inhibits it

isocitrate dehydrogenase

Reactions that replenish CAC intermediates

Anaplerotic Reactions

Another cataplerotic reaction is ___ that requires Acetyl CoA.

fatty acid biosynthesis

When the energy charge is __, oxaloacetate replenishes the CAC

low

In glyoxylate cycle, there is an incorporation of __ acetyl CoA

2

Site for glyoxylate cycle

the enzymes of the glyoxylate cycle are sequestered in membrane-bounded organelles called glyoxysomes (plants) as well as in cytoplasm (yeast and algae)

The two unique enzymes in Glyoxylate Cycle

Isocitrate Lyase
Malate Synthase