Ch. 10 Carbohydrate metabolism pt. 2

_____ contains a high-energy thioester bond that can be used to drive other reactions when hydrolysis occurs

Acetyl-CoA

how is Acetyl-CoA formed

from pyruvate via pyruvate dehydrogenase complex

pyruvate dehydrogenase is inhibited by

acetyl-CoA and NADH

pyruvate dehydrogenase (PDH) oxidized pyruvate, creating CO2; it requires ___ _____ and Mg²⁺

thiamine pyrophosphate (vitamin B₁, TPP)

____ ____ oxidizes the remaining two-carbon molecule using lipoic acid, and transfers the resulting acetyl group to CoA, forming acetyl-CoA

dihydrolipoyl transacetylase

_____ _____ uses FAD to reoxidize lipoic acid, forming FADH₂. This FADH₂ can later transfer electrons to NAD+, forming NADH that can feed into the electron transport chain (ETC)

dihydrolipoyl dehydrogenase

_____ _____ _____ phosphorylates PDH when ATP or acetyl-CoA levels are high, turning it off

pyruvate dehydrogenase kinase

_____ ______ _____ dephosphorylates PDH when ADP levels are high, turning it on

pyruvate dehydrogenase phosphatase

Acetyl-CoA can be formed from __ ___, which enter the mitochondria using carriers

fatty acids

the fatty acid couples with CoA in the cytosol to form____ ____, which moves to the intermembrane space

fatty acyl-CoA

the acyl (fatty acid) group is transferred to ___ to form acyl-carnitine, which crosses the inner membrane

carnitine

the acyl group is transferred to a mitochondrial CoA to reform fatty acyl-CoA, which can undergo ______ to form acetyl-CoA

β-oxidation

acetyl-CoA can be formed from the

• carbon skeletons of ketogenic amino acids

• ketone bodies

• alochol

the citric acid cycle (Krebs) takes place in the

mitochondrial matrix

Krebs main purpose is to

oxidize carbons in intermediates of CO2 and generate high-energy electron carriers (NADH and FADH2) and GTP

key enzymes of the Krebs cycle

• citrate synthase

• aconitase

• isocitrate dehydrogenase

• α-ketoglutarate dehydrogenase

• succinyl-CoA synthetase

• succinate dehydrogenase

• fumarase

• malate dehydrogenase

citrate synthase

couples acetyl-CoA to oxaloacetate and then hydrolyzes the resulting product, forming citrate and CoA-SH

citrate synthase is regulated by

negative feedback from ATP, NADH, succinyl-CoA, and citrate

acontiase

isomerizes citrate to isocitrate

isocitrate dehydrogenase

oxidized and decarboxylates isocitrate to from α-ketoglutarate. It generates the first CO2 and first NADH of the cycle. AS THE RATE LIMITING STEP of the Krebs cycle, it is heavily regulated

inhibitors and activators of isocitrate dehydrogenase

• inhibitors → ATP and NADH

• activators → ADP and NAD+

α-ketoglutarate dehydrogenase complex

acts similarly to PDH complex, metabolizing α-ketoglutarate to form succinyl-CoA. α-ketoglutarate dehydrogenase is an enzyme that generates the second CO2 and the second NADH of the cycle.

α-ketoglutarate dehydrogenase complex inhibitors and activators

• inhibitors → ATP, NADH, succinyl-CoA

• activators → ADP and Ca2+

succinyl-CoA synthetase

hydrolyzes the thioester bond in succinyl-CoA to form succinate and CoA-SH. generates the one GTP generated in the cycle

succinate dehydrogenase

oxidizes succinate to form fumarate. succinate dehydrogenase is a flavoprotein is anchored to the inner mitochondrial membrane because it requires FAD, which is reduced to create the one FADH2 generated in the cycle

fumarase

hydrolyzes the alkene bond of fumarate, forming malate

malate dehydrogenase

oxidizes malate to oxaloacetate (OAA) malate dehydrogenase generates the third and final NADH of the cycle

the electron transport chain (ETC) takes place on the

matrix-facing surface of the inner mitochondrial membrane

____ donates electrons to the chain, which are passed from one complex to the next. As the ETC progresses, reduction potentials increase until ____, which has the highest reduction potential, receives electrons

NADH, O2

complex 1 (NADH-CoQ oxidoreductase)

uses an iron-sulfur cluster to transfer electrons from NADH to flavin mononucleotide (FMN) and then to coenzyme Q (CoQ), forming CoQH₂. Four protons are translocated by this complex

complex 2 (succinate-CoQ oxidoreductase)

uses an iron-sulfur cluster to transfer electrons from succinate to FAD, and then to CoQ, forming CoQH₂. No proton pumping occurs in this complex

complex 3 (CoQH₂ -cytochrome c oxidoreductase)

uses an iron-sulfur cluster to transfer electrons from CoQH2 to heme, forming cytochrome c as part of the Q cycle. Four protons are translocated by this complex

complex 4 (cytochrome c oxidase)

uses cytochromes and Cu2+ to transfer electrons in the form of hydride ions (H-) from cytochrome c to oxygen, forming water. Two protons are translocated by this complex

____ cannot cross the inner mitochondrial membrane. Therefore, one of two available shuttle mechanisms to transfer electrons in the mitochondrial matrix must be used

NADH

The 2 shuttle mechanisms

• glycerol 3-phosphate shuttle

• malate-aspartate shuttle

glycerol 3-phosphate shuttle

electrons are transferred from NADH to dihydroxyacetone phosphate (DHAP), forming glycerol 3-phosphate. These electrons can then be transferred to mitochondrial FAD, forming FADH₃

malate-aspartate shuttle

electrons are transferred from NADH to oxaloacetate (OAA), forming malate. Malate can then cross the inner mitochondrial membrane and transfer the electrons to mitochondrial NAD+, forming NADH

the proton-motive force is

the electrochemical gradient generated by the electron transport chain across the inner mitochondrial membrane. The intermembrane space has a higher concentration of protons than the matrix; this gradient stores energy, which can be used to form ATP via chemiosmotic coupling

____ ___ is the enzyme responsible for generating ATP from ADP and and inorganic phosphate (P_i)

ATP synthase

the F₀ and the F₁ portion of ATP synthase

• F0→ ion channel, allowing protons to flow down the gradient from the intermembrane space to the matrix

• F1 → uses the energy released by the gradient to phosphorylate ADP into ATP

glycolysis generates

2 NADH and 2 ATP

pyruvate dehydrogenase generates

1 NADH per molecule of pyruvate. Each glucose forms two molecules of pyruvate from glycolysis, so this complex produces 2 NADH

the citric acid cycle (Krebs) generates

3 NADH, 1 FADH₂, 1GTP (6 NADH, 2 FADH₂, and 2 GTP per molecule of glucose)

each NADH yields ___ ATP; 10 NADH forms ___ 25 ATP

2.5, 25

each FADH₂ yields ___ ATP; 2 FADH₂ form ___ ATP

1.5, 3

GTP are converted to

ATP

__ ATP from glycolysis + __ ATP (GTP) from the Krebs cycle + __ATP from NADH + __ ATP from FADH₂ = 32 ATP per molecule of glucose (optimal) → inefficiencies of the system and variability between cells make 30-31 ATP/glucose

2,2,25,3