Biochemistry Chapter 8: Glycolysis Quiz

Unit II: Intermediary Metabolism

• Glycolysis is a metabolic pathway occurring in all tissues
• Glucose is broken down to generate ATP and other metabolic intermediates
• It's the central pathway for carbohydrate metabolism, converting various sugars into glucose
• Pyruvate is the end product of glycolysis in the presence of oxygen (aerobic)
• In the absence of oxygen (anaerobic), pyruvate is converted to lactate.

Chapter 8: Glycolysis

• Glycolysis is a metabolic pathway occurring in all tissues
• Glucose is transformed into energy (ATP) and other metabolic intermediates
• Glucose metabolism is a central hub, converting dietary and catabolic sugars into glucose
• Pyruvate is the end product of aerobic glycolysis in cells with mitochondria and sufficient oxygen
• In anaerobic conditions where there's limited oxygen or no mitochondria, glucose is converted into pyruvate, and NADH reduces it to lactate, producing energy

IV. Transport of glucose into cells

• Glucose requires specific transporters to cross cell membranes.
• There are 14 glucose transporter families (GLUTs)
• GLUT transporters are characterized by their unique tissue distribution and regulation.
• GLUT-1 is high in erythrocytes and blood brain barrier, with varying levels in other tissues
• GLUT-2 is present in liver, kidney, and pancreatic beta cells.
• GLUT-3 is primarily found in neurons.
• GLUT-4 is insulin-dependent and found in muscle and adipose tissue.

B. Na+-monosaccharide cotransporter system

• Sodium-dependent glucose transporters (SGLTs) move glucose against its concentration gradient.
• These transporters are crucial in the absorption of glucose from the gut and certain other tissues.
• They are located in the intestinal tract, renal tubules, and choroid plexus.

V. Reactions of glycolysis

• Glycolysis occurs in two stages: an energy investment phase and an energy generation phase.
• In the initial (energy investment) phase, glucose is phosphorylated at the expense of ATP investment.
• The subsequent phase (energy generation) results in the generation of ATP via substrate-level phosphorylation.

A. Phosphorylation of glucose

• Glucose phosphorylation is a crucial step for trapping glucose inside the cell, preventing its diffusion back out.
• Hexokinase is the primary enzyme responsible for glucose phosphorylation, with four isozymes (I-IV)
• Hexokinases I-III have high affinity for glucose.
• Hexokinase IV (glucokinase) is found in the liver and pancreatic beta cells.
• Glucokinase is importantly regulated by glucose concentration
• Hexokinase IV has a higher Km (lower affinity) for glucose than the other isozymes.

2. Hexokinase IV (Glucokinase)

• Glucokinase functions as a glucose sensor for insulin secretion in pancreatic beta cells.
• It also regulates glucose metabolism in hepatocytes (liver cells).
• The enzyme's high Km ensures it's only active at high glucose concentrations.
• It is also important in regulating glucose homeostasis.
• It plays a key role during a high carbohydrate meal
• It is involved in controlling hyperglycemia

b. Regulation by fructose 6-phosphate and glucose

• Glucokinase activity isn't allosterically inhibited by G-6-P like other hexokinases.
• It is regulated indirectly by fructose 6-phosphate.
• The regulatory protein, GKRP, regulates the activity of glucokinase in the liver.

c. Regulation by fructose 6-phosphate

• Phosphofructokinase-1 (PFK-1) is the key regulatory enzyme in glycolysis.
• The activity of PFK1 is modulated by different compounds.
• PFK-1 is inhibited by high ATP and citrate concentrations, reflecting high energy levels in the cell.
• PFK-1 is activated by high AMP and fructose 2,6-bisphosphate (F-2,6-BP).

2. Regulation by fructose 2,6-bisphosphate

• Fructose 2,6-bisphosphate (F-2,6-BP) is a potent allosteric regulator of PFK-1 and plays a central role in the regulation of glycolysis and gluconeogenesis.
• F-2,6-BisP is synthesized from fructose-6-phosphate by phosphofructokinase 2 (PFK-2.)

VII. Alternate fates of pyruvate

• Pyruvate can be oxidized to acetyl-CoA, entering the citric acid cycle.
• It can also be carboxylated to oxaloacetate, a precursor for gluconeogenesis.
• In certain microorganisms, pyruvate can be reduced to ethanol.

K. Reduction of pyruvate to lactate

• Lactate is the end product of anaerobic glycolysis in certain tissues, such as exercising muscles and red blood cells.
• The conversion of pyruvate to lactate is catalyzed by lactate dehydrogenase (LDH)

3. Lactic acidosis

• Lactic acidosis occurs when the production of lactate exceeds the body's capacity to utilize or remove it.
• This can be caused by various factors, including circulatory collapse, tissue hypoxia, and certain diseases.
• High levels of lactate in blood indicate a disruption in cellular metabolism and require medical attention.

L. Energy yield from glycolysis

• Glycolysis produces a small amount of ATP but most of the energy is stored in pyruvate or lactate.
• The citric acid cycle is required to release the energy stored in these compounds.