PDH Complex and TCA Cycle support anabolic and oxidative chemistries

What metabolic substrates yield pyruvate from glycolysis

Carbohydrates

What are the two key fates of pyruvate

Conversion to oxaloacetate and acetyl CoA

What enzyme converts pyruvate to oxaloacetate

Pyruvate carboxylase which is biotin dependent

What complex converts pyruvate to acetyl CoA

Pyruvate dehydrogenase complex (PDH) with 5 coenzymes

What two molecules combine to form citrate

Oxaloacetate and acetyl CoA

What must happen to proteins before their carbon skeletons enter metabolism

Removal of the alpha amino group

What do proteins produce after removal of the amino group

Alpha keto acids

Which amino acids yield acetyl CoA (ketogenic substrates)

Leucine and Lysine exclusively and Phe Tyr Trp Ile Thr partially

Which amino acids yield intermediates that enter the TCA cycle (glucogenic substrates)

Gly Ala Ser Cys Glu Gln Asp Asn Pro Met Arg His Val exclusively and Phe Tyr Trp Ile Thr partially

What is the source of acetyl CoA from fatty acids

Beta oxidation

What reduced cofactors are produced during beta oxidation

FADH2 and NADH

How do ketone bodies produce acetyl CoA

By cleavage of acetoacetyl CoA into two acetyl CoA molecules

Where are ketone bodies produced and from what

In the liver from excess acetyl CoA from beta oxidation and ketogenic amino acids

Which TCA intermediate supports gluconeogenesis

Malate

Which amino acids are formed as products of the urea cycle and TCA intermediates

Glu Gln Asp Asn and Arg

Which intermediate is used for porphyrin ring synthesis

Succinyl CoA

What is the function of citrate in anabolic pathways

Precursor for de novo fatty acid and cholesterol synthesis

Which enzymes catalyze oxidative decarboxylation steps in the TCA cycle

Isocitrate dehydrogenase and alpha ketoglutarate dehydrogenase complex

Which TCA cycle enzyme catalyzes the substrate-level phosphorylation producing GTP

Succinyl CoA synthetase

Which TCA enzyme is also Complex II of the ETC

Succinate dehydrogenase

What is the role of aconitase in the TCA cycle

Isomerization of citrate to isocitrate via dehydration and hydration

Which coenzyme is involved in the PDH complex and TCA dehydrogenase reactions

Thiamine pyrophosphate (TPP) among others including lipoic acid CoA FAD and NAD+

What allosterically activates isocitrate dehydrogenase

ADP and Ca2+

What allosterically inhibits isocitrate dehydrogenase

ATP and NADH

What allosterically activates alpha ketoglutarate dehydrogenase complex

Ca2+

What inhibits alpha ketoglutarate dehydrogenase complex

NADH and succinyl CoA

What happens during the reaction catalyzed by malate dehydrogenase

Oxidation of malate to oxaloacetate producing NADH

Is the reaction catalyzed by succinyl CoA synthetase reversible or irreversible

Reversible

What is a key regulatory feature of citrate synthase

Citrate competitively inhibits it by blocking oxaloacetate binding

What is the significance of maintaining oxaloacetate levels in the TCA cycle

OAA is required to combine with acetyl CoA to keep the cycle running efficiently

Why does no ATP directly form in the TCA cycle itself

Energy is captured in NADH FADH2 and GTP instead for later use in oxidative phosphorylation

What is the difference between GTP and ATP in the TCA cycle

GTP is produced by substrate-level phosphorylation but can be converted to ATP in the cell

How does the TCA cycle support anabolic processes

By providing intermediates like citrate alpha ketoglutarate and oxaloacetate for biosynthesis

Which TCA intermediate supports amino acid synthesis like glutamate and glutamine

Alpha ketoglutarate

How does succinate dehydrogenase link the TCA cycle to the electron transport chain

It is part of Complex II and transfers electrons from succinate oxidation to the ETC

What happens to citrate when it accumulates in excess in a fed state

It is exported to cytosol for fatty acid and cholesterol synthesis

Why is pyruvate carboxylase biotin dependent

Biotin acts as a CO2 carrier for the carboxylation reaction

What coenzymes are required by the pyruvate dehydrogenase complex

TPP lipoic acid CoA FAD NAD+

What are the steps in the aconitase reaction

Dehydration to form cis-aconitate followed by hydration to isocitrate

How does calcium act in the regulation of the TCA cycle

It allosterically activates isocitrate dehydrogenase and alpha ketoglutarate dehydrogenase

Why is succinyl CoA synthetase important in energy metabolism

It produces GTP via substrate-level phosphorylation

What is the role of fumarase in the TCA cycle

Hydrates fumarate to malate

How does malate dehydrogenase maintain TCA cycle flux

By oxidizing malate to regenerate oxaloacetate

What effect does high NADH concentration have on the TCA cycle

It inhibits key dehydrogenases slowing the cycle

Why is the reaction catalyzed by citrate synthase irreversible

Because it releases Coenzyme A and forms a stable citrate molecule

What is the metabolic fate of ketogenic amino acids

They are converted into acetyl CoA or acetoacetate for energy or ketone body production

How are glucogenic amino acids utilized in metabolism

They are converted into TCA cycle intermediates for gluconeogenesis or energy

What is the biochemical importance of the TCA cycle being amphibolic

Because it functions in both energy production and biosynthesis

What is the role of pyruvate in connecting glycolysis and the TCA cycle

Pyruvate is converted to acetyl CoA to enter the TCA cycle

How does removal of the alpha amino group from amino acids facilitate their catabolism

It allows the carbon skeleton to enter metabolic pathways as keto acids

Which enzyme complex catalyzes the oxidative decarboxylation of alpha ketoglutarate

Alpha ketoglutarate dehydrogenase complex

What coenzymes are shared between the PDH complex and alpha ketoglutarate dehydrogenase complex

TPP lipoic acid CoA FAD NAD+

How does substrate-level phosphorylation occur in the TCA cycle

Succinyl CoA synthetase converts succinyl CoA to succinate producing GTP

Why is succinate dehydrogenase unique among TCA enzymes

It is embedded in the inner mitochondrial membrane and part of ETC Complex II

What is the consequence of excessive citrate accumulation in the cytosol

Citrate promotes fatty acid synthesis and inhibits glycolysis

How does acetyl CoA availability influence pyruvate metabolism

High acetyl CoA promotes pyruvate carboxylation to oxaloacetate rather than conversion to acetyl CoA

What is the biochemical function of fumarase

It catalyzes the hydration of fumarate to malate

Why is the malate to oxaloacetate reaction critical for the TCA cycle

It regenerates oxaloacetate allowing the cycle to continue

How does ADP regulate the TCA cycle

ADP activates isocitrate dehydrogenase increasing cycle flux

How does NADH regulate the TCA cycle

NADH inhibits key dehydrogenases decreasing cycle flux

What is the role of calcium ions in TCA cycle regulation

Calcium activates isocitrate dehydrogenase and alpha ketoglutarate dehydrogenase to enhance energy production

Why does the TCA cycle produce CO2

From oxidative decarboxylation steps that release carbon atoms as CO2

What happens to the carbons from acetyl CoA in the TCA cycle

They are released as CO2 over two cycles

How is ATP production linked to the TCA cycle

Via NADH and FADH2 produced by the cycle that feed electrons into oxidative phosphorylation

What is the significance of the GTP produced in the TCA cycle

It can be readily converted to ATP for cellular energy

How do ketogenic and glucogenic amino acids differ in their metabolic fates

Ketogenic amino acids yield acetyl CoA or ketone bodies glucogenic yield TCA cycle intermediates or glucose

What is the effect of succinyl CoA on alpha ketoglutarate dehydrogenase

Succinyl CoA acts as an allosteric inhibitor

What is the primary purpose of the pyruvate dehydrogenase complex

To convert pyruvate into acetyl CoA for entry into the TCA cycle

How does the PDH complex regulate the link between glycolysis and the TCA cycle

It controls flux by converting pyruvate to acetyl CoA based on energy needs

Which vitamin-derived coenzyme is essential for PDH complex function

Thiamine pyrophosphate (TPP)

What role does lipoic acid play in the PDH complex

Lipoic acid acts as a swinging arm transferring acyl groups between active sites

How does NAD+ function in the PDH complex

NAD+ accepts electrons to become NADH during pyruvate oxidation

What is the relationship between TCA cycle intermediates and amino acid biosynthesis

Intermediates serve as precursors for non-essential amino acids

Why is citrate considered a metabolic hub

Citrate links energy production to fatty acid and cholesterol synthesis

What enzyme catalyzes the first step of the TCA cycle

Citrate synthase

How does ATP influence citrate synthase activity

High ATP inhibits citrate synthase to slow the cycle

Why is the aconitase reaction important in the TCA cycle

It converts citrate to isocitrate to allow oxidative decarboxylation steps

What is the significance of the oxidative decarboxylation of isocitrate

It produces NADH and CO2 and reduces the carbon count by one

What happens in the oxidative decarboxylation of alpha ketoglutarate

Alpha ketoglutarate is converted to succinyl CoA producing NADH and CO2

How does the succinyl CoA synthetase reaction contribute to cellular energy

It generates GTP via substrate-level phosphorylation

What distinguishes FADH2 from NADH in energy metabolism

FADH2 enters the ETC at Complex II producing fewer ATP than NADH

Why is succinate dehydrogenase integral to both TCA cycle and ETC

It oxidizes succinate and passes electrons to the ETC at Complex II

How does fumarase contribute to maintaining TCA cycle continuity

By hydrating fumarate to malate to continue the cycle

What critical role does malate dehydrogenase play in the TCA cycle

It regenerates oxaloacetate and produces NADH

How is the activity of TCA cycle enzymes coordinated

Through allosteric regulation by energy charge molecules like ATP ADP NADH and Ca2+

What effect does high cellular energy status have on the TCA cycle

High ATP and NADH inhibit key enzymes to reduce cycle flux

Why is the TCA cycle called amphibolic

It functions in both catabolic energy production and anabolic biosynthesis

How do ketone bodies contribute to energy metabolism

Ketone bodies provide acetyl CoA especially during fasting or starvation