Carbohydrate Metabolism 2

Flashcards covering key vocabulary terms and definitions related to carbohydrate metabolism, glycolysis, the Warburg effect, shuttle systems, the PDH complex, and their regulation, based on the provided lecture notes.

Glycolysis

The initial stage of glucose metabolism, occurring in the cytosol without oxygen, producing 2 ATPs, 2 NADH/H+, and pyruvate.

PDH Complex

Pyruvate Dehydrogenase Complex; links glycolysis to the TCA cycle by converting pyruvate into acetyl-CoA in the mitochondrial matrix.

Warburg Effect

A phenomenon where cancer cells primarily produce energy by a high rate of glycolysis followed by lactic acid fermentation (aerobic glycolysis) rather than by oxidation of pyruvate in the mitochondria, even in the presence of oxygen.

Cancer cells and glucose

These cells need more glucose than normal cells and often overexpress GLUT transporters to meet their energy demands via the Warburg Effect.

alpha-amylase

An enzyme responsible for breaking down starch into oligosaccharides (2-3 glucose units) in the digestive system.

Fed State

A metabolic state after consuming carbohydrates, where glucose is metabolized through glycolysis, stored as glycogen, or converted to acetyl-CoA, triglycerides, and VLDL.

Substrate-level phosphorylation

A type of metabolic reaction that directly generates ATP by transferring a phosphate group from a substrate molecule to ADP.

Aerobic cells (Glycolysis outcome)

In these cells, pyruvate is transported into mitochondria and oxidized by O2 to CO2, generating a large amount of ATP (36-38 mol ATP per mol glucose).

Anaerobic cells (Glycolysis outcome)

In these cells, pyruvate is reduced to lactate to regenerate NAD+, producing a net of 2 mol ATPs per mol glucose.

Glycolysis (functions beyond ATP)

Provides precursors for lipid biosynthesis in liver and adipose tissue, and precursors for some amino acids and pentoses.

Preparative phase of Glycolysis

The initial stage of glycolysis where glucose is converted to fructose-1,6-bisphosphate, consuming 2 ATPs.

ATP-generating phase of Glycolysis

The later stage of glycolysis where triosephosphates are converted to pyruvate, producing 4 ATPs and 2 NADH/H+.

Hexokinase (Glucokinase)

The first enzyme in the glycolytic pathway that converts glucose to glucose-6-phosphate (G6P) using ATP.

Kinases

Phosphorylating enzymes that transfer a phosphate group from ATP to a substrate molecule.

Glucose-6-phosphate (G6P)

A central intermediate for many catabolic and anabolic pathways, formed from glucose by hexokinase.

Phosphofructokinase-1 (PFK-1)

The third and most regulated enzyme of the glycolytic pathway, converting fructose-6-phosphate into fructose-1,6-bisphosphate (FBP) using ATP.

Pyruvate Kinase

An enzyme involved in the final step of glycolysis, converting phosphoenolpyruvate (PEP) to pyruvate and generating ATP through substrate-level phosphorylation.

NAD+/NADH

A co-factor that carries two protons and two electrons; its reduced form (NADH) contains energy equivalent to 3 ATPs when converted in the mitochondrial respiratory chain.

Shuttle systems (Glycerol-3-phosphate, Malate-aspartate)

Mechanisms (like the glycerol-3-phosphate shuttle and malate-aspartate shuttle) that transfer reduced co-factors (NADH) from the cytosol into the mitochondrial matrix because NADH cannot cross the mitochondrial membrane directly.

Redox reaction

A chemical reaction involving the transfer of electrons, where reduction is the gain of protons and electrons, and oxidation is the loss of them.

Transamination reaction

Mutual conversions of amino groups into keto groups, as seen in the malate-aspartate shuttle.

Pyruvate Dehydrogenase Complex (PDH)

A multi-enzyme complex in the mitochondrial matrix that converts pyruvate into acetyl-CoA, linking glycolysis to the TCA cycle and yielding one mol NADH/H+ per mol pyruvate.

Thiamine Pyrophosphate (TPP)

A co-enzyme of the PDH complex that binds the aldehyde generated from the decarboxylation of pyruvate.

Lipoic Acid (Lipoate)

A co-enzyme of the PDH complex that acts as a transferring 'crane arm' between TPP and co-enzyme A, transferring the acetyl-residue.

Coenzyme A (CoASH)

A co-enzyme that forms an energy-rich thioester bond with the product of the PDH reaction, becoming acetyl-CoA.

Thioesters

Energy-richer than normal esters or carboxylic acids due to the inability of free electrons at the sulfur to undergo mesomerism.

Pantothenate (Vitamin B5)

The vitamin precursor for Co-enzyme A.

Thiamine (Vitamin B1)

The vitamin precursor for Thiamine Pyrophosphate (TPP).

Riboflavin (Vitamin B2)

The vitamin precursor for FAD.

Niacin (Vitamin B3 / Nicotinic Acid)

The vitamin precursor for NAD+.

Anaerobic glycolysis locations

Occurs in red blood cells (sole energy source), muscle cells under stress, and cancer cells due to oxygen deficiency or limited mitochondrial capacity.

Yeast anaerobic metabolism

NADH from glycolysis is re-oxidized by alcohol dehydrogenase, with acetaldehyde (from pyruvate decarboxylase) as a substrate, yielding two ATPs per glucose.

Adenylate kinase

An enzyme that catalyzes the reaction 2 ADP -> AMP + ATP, providing a better indicator of cellular ATP utilization through AMP levels.

Cori Cycle

A metabolic pathway that involves cooperation between aerobic liver cells and anaerobic cells (like red blood cells or active muscle) to recycle lactate back into glucose.

Regulation of Hexokinase

Characterized by a high KM for glucose, most active after meals, and induced by insulin.

Regulation of PFK-1

The rate-limiting enzyme of glycolysis, allosterically inhibited by ATP or citrate, and stimulated by AMP, ADP, or fructose-2,6-bisphosphate.

Regulation of Pyruvate Kinase

Inhibited by phosphorylation during fasting (glucagon), activated by dephosphorylation (insulin) and fructose-1,6-bisphosphate (feed-forward mechanism), and allosterically inhibited by alanine and ATP.

Pyruvate Dehydrogenase Complex (PDH) Regulation

Activated by ADP and Ca2+, and inhibited by NADH and Acetyl CoA.