M2C: Kreb's Cycle

β-oxidation

the metabolism that fatty acids undergo to produce acetyl-CoA, which then enters the citric acid cycle.

What do fatty acids with an even number of carbons produce?

only acetyl-CoA

What do fatty acids with an odd number of carbons produce?

acetyl-CoA and propionyl-CoA

How do we regenerate oxaloacetate after it reacts with acetyl-CoA to form citrate even though it is unfavorable to proceed forward?

Due to the continuous removal of oxaloacetate by its reaction with acetyl-CoA to form citrate, and the continuous re-oxidation of NADH in the ETC, favor oxaloacetate formation via malate dehydrogenase.

Succinate Dehydrogenase

- Aka Complex II
- Unlike other citric acid cycle enzymes, it is bound to the inner mitochondrial membrane (think "inside job")
- It catalyzes the first dehydrogenation reaction, forming fumarate.
- The enzyme contains flavin adenine dinucleotide (FAD), an electron carrier.
- It is part of the citric acid cycle and involved in the ETC
- Is the only oxidative phosphorylation complex to lack subunits encoded by the mitochondrial genome. Instead, it consists of four subunits encoded by the nuclear genome.

When the CoA of succinyl-CoA is replaced by a phosphate group, where can the phosphate group go?

- It is transferred to ADP to make ATP.
- In some cells, guanosine diphosphate (GDP) is used instead of ADP, forming guanosine triphosphate (GTP) as a product.
- Occurs in the 5th step of the Krebs cycle

How many hydrogen atoms (and their electrons) are transferred to FAD?

- Two hydrogen atoms—with their electrons—are transferred to FAD, producing FADH2
- Occurs in the 6th step of the Krebs cycle

Pyruvate dehydrogenase

- First component enzyme of the pyruvate dehydrogenase complex (PDC).
- Links the glycolysis to the citric acid cycle and releases energy via NADH.

Pyruvate decarboxylation

- The process where PDC contributes to transforming pyruvate into acetyl-CoA
- Acetyl-CoA may then be used in the citric acid cycle to carry out cellular respiration.

How are α-Ketoglutarate dehydrogenase and pyruvate dehydrogenase functionally similar?

- They are both oxidative decarboxylation enzymes
- They require the same cofactors, as follows:
Thiamine pyrophosphate (TPP) (requires vitamin B1 (thiamine)),
Lipoic acid,
Coenzyme A (CoA),
FAD (requires vitamin B2 (riboflavin)), and
Nicotinamide adenine dinucleotide (NAD+) (requires vitamin B3 (niacin))

What will a thiamine deficiency do?

- Will affect the functioning of different vitamin B1 - requiring enzymes like α-ketoglutarate dehydrogenase.
- Ex. beriberi

Pyruvate Dehydrogenase Complex

- Catalyzes the conversion of pyruvate to acetyl-CoA.
- It contains multiple copies of three enzymes and requires five cofactors
- Enzymes: pyruvate decarboxylase (aka pyruvate dehydrogenase), dihydrolipoyl transacetylase, and dihydrolipoyl dehydrogenase
- Cofactors: thiamine (B1), lipoic acid, CoA, FAD, and NAD+
- PDH kinase and PDH phosphatase regulate the complex by acting on pyruvate decarboxylase

What activates the Pyruvate Dehydrogenase Complex?

PDH phosphatase activates the PDC via dephosphorylation of pyruvate decarboxylase

What deactivates the Pyruvate Dehydrogenase Complex?

PDH kinase phosphorylates the PDH complex, rendering pyruvate decarboxylase inactive.

What intermediates of the Citric Acid Cycle can be used elsewhere?

α-ketoglutarate and succinyl coenzyme A

How is α-ketoglutarate used outside of the Citric Acid Cycle?

- It participates in ammonia metabolism (which is important since ammonia is toxic to the central nervous system (CNS))
- Glutamate can uptake an ammonia group, metabolic waste, via glutamine synthetase to make glutamine. Glutamine is a nontoxic courier of ammonia.
- We are able to form glutamate because amino acids can transfer their amino group to α-ketoglutarate via aminotransferases.

How is succinyl coenzyme A used outside of the Citric Acid Cycle?

It forms the building blocks of heme, as succinyl-CoA and glycine combine to form δ-aminolevulinic acid (ALA), the first committed intermediate of the pathway