Glucose Metabolism Exam #1 Study Guide

Flashcards covering key vocabulary terms related to glucose transport, glycolysis, fructose metabolism, TCA cycle, pentose phosphate pathway, and gluconeogenesis, based on the provided lecture notes.

GLUT2

A protein carrier for glucose, galactose, and fructose, primarily found in the liver, pancreatic beta cells, kidneys, and basolateral membrane of intestinal enterocytes. It functions via facilitated diffusion and is activated when blood glucose is high, allowing glucose to enter or exit.

GLUT4

An insulin-responsive glucose transporter found in the plasma membrane of adipose tissue and muscle cells, permitting increased glucose intake. Its translocation to the cell surface is triggered by insulin binding to receptors.

First Tier Insulin Response

Mediated by GLUT2, it involves pancreatic B-cells detecting high blood glucose and releasing insulin, and GLUT2 facilitating glucose entry into hepatocytes for glycogen and fatty acid synthesis. Tissues involved are pancreatic B-cells and liver.

Second Tier Reduction of Glucose

Mediated by GLUT4, it involves insulin-stimulated GLUT4 translocation to the cell surface of skeletal and adipose tissue, which increases glucose uptake into these cells from the bloodstream. Tissues involved are skeletal muscle and adipose tissue.

Fed State (Glucose Metabolism)

Characterized by elevated blood glucose, stimulating the pancreas to release insulin (triggered by GLUT2). Insulin promotes glucose uptake by tissues via GLUT4, and in the liver, GLUT2 facilitates glucose entry for storage as glycogen or conversion to fatty acids.

Fasted State (Glucose Metabolism)

The liver releases stored glucose through glycogenolysis and produces new glucose through gluconeogenesis. The body shifts to using fatty acids and ketone bodies as alternative fuels.

Defective GLUT2

Leads to elevated glucose levels, hinders glucose sensing in pancreatic B-cells (reducing insulin secretion), and causes reduced hepatic glucose uptake, perpetuating high glucose in circulation.

Defective GLUT4

Prevents muscle and adipose tissue from effectively taking up glucose. This leads to increased insulin levels as the pancreas produces more insulin in an attempt to lower glucose, a characteristic seen in Type 1 diabetes where cells do not respond.

Glycolysis

The first step in glucose utilization, occurring in the cytosol of all cell types. It converts glucose into pyruvate, with an overall net gain of 2 ATP.

Glycolysis Priming Phase

An initial phase of glycolysis that requires ATP to convert glucose into glyceraldehyde-3-phosphate.

Glycolysis Paying Off Phase

A later phase of glycolysis that generates ATP and reducing equivalents (NADH).

Aerobic Glycolysis Products

Pyruvate and a net gain of 2 ATP.

Anaerobic Glycolysis Products

Lactate and a net gain of 2 ATP.

Hexokinase

An enzyme catalyzing the initial irreversible step of glycolysis, converting glucose to glucose-6-phosphate. It is inhibited by glucose-6-phosphate.

Glucokinase

An enzyme present in the liver and pancreatic beta cells that phosphorylates glucose to glucose-6-phosphate. It is activated by fructose-1-phosphate, glucose, and insulin, and inhibited by fructose-6-phosphate.

Phosphofructokinase (PFK)

A major rate-limiting enzyme in glycolysis, converting fructose-6-phosphate to fructose-1,6-bisphosphate. Also referred to as 6-Phosphofructo-1-Kinase.

Pyruvate Kinase

An enzyme catalyzing the irreversible step of glycolysis, converting phosphoenolpyruvate to pyruvate. It is activated by fructose-1,6-bisphosphate.

Pyruvate (Liver Fed State)

Decarboxylated to acetyl-CoA by Pyruvate Dehydrogenase (PDH), which then enters the TCA cycle for energy production or fatty acid synthesis.

Pyruvate (Liver Fasted State)

Converted to lactate, which is then used as a gluconeogenic precursor to produce new glucose.

Pyruvate (Red Blood Cells)

Converted to lactate to regenerate NAD+ for continuous glycolysis, as RBCs lack mitochondria and cannot oxidize pyruvate for the TCA cycle.

Fructose Metabolism

Primarily occurs in the liver, where fructose is phosphorylated by fructokinase and cleared by Aldolase B to enter glycolytic pathways. It bypasses the phosphofructokinase-1 (PFK-1) step and does not stimulate insulin secretion.

High Fructose Intake Effects

Can promote lipogenesis and fatty acid synthesis in the liver because bypassing the PFK-1 step allows uncontrolled entry of fructose metabolites into pathways that generate acetyl-CoA, a precursor for triglyceride formation, potentially leading to fatty liver and obesity.

Pyruvate Dehydrogenase (PDH) Complex

An enzyme complex that catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA, linking glycolysis to the TCA cycle. It occurs in the mitochondria and is regulated by acetyl-CoA and NADH (feedback inhibition) and inhibited by high energy status.

Acetyl-CoA (after PDH Complex)

Can enter the TCA cycle, serve as a building block for lipogenesis (fatty acid synthesis), ketone body production, or cholesterol synthesis.

TCA Cycle (Tricarboxylic Acid Cycle)

Also known as the Krebs cycle or citric acid cycle. It oxidizes acetyl-CoA into CO2 and H2O, produces NADH and FADH2, and acts as a central hub linking catabolic and anabolic pathways. One molecule of Acetyl-CoA yields 3 NADH, 1 FADH2, and 1 GTP (equivalent to ATP).

Pentose Phosphate Pathway

An alternative route for glucose-6-phosphate metabolism. Its main functions are to produce NADPH (for reductive biosynthesis and protection against oxidative stress) and Ribose-5-Phosphate (for DNA and RNA synthesis).

Gluconeogenesis

The process of producing new glucose from non-carbohydrate precursors, primarily pyruvate. It occurs in the fasted state when blood glucose levels are low, mainly in the liver and sometimes the kidneys.

Pyruvate Carboxylase (Gluconeogenesis)

An enzyme in mitochondria that converts pyruvate to oxaloacetate, part of Bypass 1 in gluconeogenesis (Pyruvate to Phosphoenolpyruvate). It is regulated by Acetyl-CoA.

Phosphoenolpyruvate Carboxykinase (PEPCK)

A cytosolic enzyme that converts oxaloacetate to phosphoenolpyruvate, completing Bypass 1 in gluconeogenesis. Its activity is controlled by genes and influenced by glucagon.

Fructose-1,6-bisphosphatase (Gluconeogenesis)

An enzyme that converts Fructose-1,6-bisphosphate to Fructose-6-Phosphate, part of Bypass 2 in gluconeogenesis. It is inhibited by Fructose-2,6-bisphosphate.

Glucose-6-phosphatase (Gluconeogenesis)

An enzyme located in the endoplasmic reticulum that converts Glucose-6-phosphate to Glucose, part of Bypass 3 in gluconeogenesis. Its activity increases in the fasted state and is hormonally regulated, with insulin decreasing its activity.

Liver (Glucose Homeostasis)

The primary organ for maintaining systemic glucose homeostasis, balancing hepatic glucose production (through glycogenolysis and gluconeogenesis) and utilization. It releases glucose into the bloodstream via Glucose-6-phosphatase.

Kidneys (Glucose Homeostasis)

Capable of producing glucose, particularly from lactate, especially during prolonged fasting or in conditions of metabolic stress.

6-Phosphofructo-1-Kinase (PFK-1)

A key regulatory enzyme in glycolysis, activated by Fructose-2,6-bisphosphate and influenced by insulin. It converts Fructose-6-phosphate to Fructose-1,6-bisphosphate.