Metabolism and Energy Homeostasis – Comprehensive Review

These flashcards review fundamental concepts of metabolism, hormonal regulation, energy expenditure, and metabolic disease, providing a thorough set of Q&A prompts for exam preparation.

What is metabolism?

All chemical reactions and pathways that occur in the body to maintain life, coordinated to regulate processes and maintain energy homeostasis.

What are the two major categories of metabolic reactions?

Catabolic reactions that break down macronutrients to generate ATP, and anabolic reactions that build complex molecules using ATP.

Which two intermediates connect many metabolic pathways?

Pyruvate and acetyl-CoA.

What primarily determines the direction of a metabolic pathway?

The cell’s energy status, reflected by levels of ATP, ADP, AMP, acetyl-CoA, citrate, and malonyl-CoA.

Where are regulatory enzymes usually located within a metabolic pathway?

At key, often irreversible, steps.

How are most metabolic regulatory enzymes controlled?

Allosterically; some are also controlled by covalent modification such as phosphorylation.

Which metabolites signal low cellular energy status?

Low acetyl-CoA, citrate, ATP, malonyl-CoA, and high ADP, AMP.

Which metabolites signal high cellular energy status?

High acetyl-CoA, citrate, ATP, and malonyl-CoA.

What is the metabolic role of malonyl-CoA?

It regulates fatty acid metabolism by inhibiting CPT-I, thereby preventing long-chain fatty acids from entering mitochondria for β-oxidation.

How does AMPK activity affect malonyl-CoA levels?

High AMP activates AMPK, which inhibits ACC, lowers malonyl-CoA, increases CPT-I activity, and enhances fatty acid oxidation.

When energy is abundant, how is malonyl-CoA affected?

ACC converts acetyl-CoA to malonyl-CoA, promoting fatty acid synthesis and inhibiting β-oxidation.

What activates AMP-activated protein kinase (AMPK)?

A low ATP/high AMP ratio, certain dietary phytochemicals, and the drug metformin.

List three major effects of activated AMPK.

Increases GLUT4 translocation, enhances fatty acid uptake (via CD36), and suppresses fatty acid synthesis while promoting catabolic ATP-producing pathways.

Where does glycolysis occur and how is it classified?

In the cytosol of all tissues; it is an amphibolic pathway.

What are the tissue, compartment, and type of gluconeogenesis?

Occurs in liver and kidneys; partly in mitochondria and cytosol; anabolic.

Where does β-oxidation take place?

In mitochondria of liver and muscle; it is a catabolic pathway.

Which pathway generates ketone bodies and where?

Ketogenesis in the cytosol of liver cells; anabolic.

Why can’t humans convert fatty acids into carbohydrate?

Because the pyruvate → acetyl-CoA reaction is irreversible, preventing net conversion of acetyl-CoA (from fat) back to glucose.

Which portions of fat CAN contribute to gluconeogenesis?

The glycerol backbone of triglycerides and propionyl-CoA from odd-chain fatty acids.

Define glucogenic amino acids.

Amino acids whose carbon skeletons can be converted into glucose via gluconeogenesis.

Why is the TCA cycle considered amphibolic?

It serves both catabolic functions (energy release) and anabolic functions (providing biosynthetic precursors).

Name two TCA intermediates that link to amino acid metabolism.

α-Ketoglutarate (precursor to glutamate) and oxaloacetate (precursor to aspartate).

How does citrate connect carbohydrate and lipid metabolism?

Citrate exits mitochondria and is cleaved into oxaloacetate and acetyl-CoA; the acetyl-CoA is used for fatty acid synthesis in the cytosol.

What role does malate play in fatty acid synthesis?

Malate can be converted to pyruvate, generating NADPH required for fatty acid synthesis.

State the liver’s central metabolic roles.

Processes and distributes fuels, stores glycogen, performs gluconeogenesis, synthesizes lipoproteins, and carries out amino acid metabolism.

What are the main fuels for skeletal muscle?

Glucose and fatty acids; muscle can also utilize ketone bodies during fasting.

Why can red blood cells rely only on glucose for energy?

They lack mitochondria and thus depend on anaerobic glycolysis.

Contrast hexokinase and glucokinase by tissue distribution and affinity for glucose.

Hexokinase is in most tissues, has low Km (high affinity) and is inhibited by G6P; glucokinase is in liver and pancreatic β-cells, has high Km (low affinity) and is not inhibited by G6P.

What hormonal profile characterizes the fed state (0–3 h post-meal)?

High insulin and low glucagon.

List three key metabolic processes dominant in the fed state.

Glycogenesis, glycolysis, lipogenesis (and protein synthesis).

During the post-absorptive state (3–18 h), what is the primary source of blood glucose?

Hepatic glycogenolysis.

Name two major substrates for gluconeogenesis in the post-absorptive state.

Lactate (Cori cycle) and alanine (glucose-alanine cycle); glycerol also contributes.

What is the main glucose source during the fasting state (18–48 h)?

Gluconeogenesis from amino acids, glycerol, and lactate.

Which fuel becomes increasingly important during prolonged fasting/starvation?

Ketone bodies from hepatic ketogenesis.

What is the primary metabolic goal during starvation (>48 h)?

To spare protein to preserve essential functions; the brain shifts to ketone bodies to reduce glucose demand.

Which hormone is considered the master anabolic regulator?

Insulin.

Which hormones are primary catabolic regulators?

Glucagon, epinephrine, and cortisol.

How does insulin affect glycogenesis?

It increases glycogenesis in liver and skeletal muscle.

What is the effect of glucagon on hepatic glycogenolysis?

Glucagon stimulates glycogenolysis in the liver.

How does epinephrine influence lipolysis?

Epinephrine increases lipolysis in adipose tissue and skeletal muscle.

Name the three major components of total energy expenditure (TEE).

Basal metabolic rate (BMR), thermic effect of food (TEF), and physical activity.

Which component contributes the most to TEE in most individuals?

Basal metabolic rate (50–70 % of TEE).

Which macronutrient has the highest thermic effect of food (TEF)?

Protein (about 20–30 %).

What is the respiratory quotient (RQ) for pure carbohydrate oxidation?

1.0.

What does an RQ of 0.7 indicate?

Predominant oxidation of fat.

What RQ value is typical for protein oxidation?

Approximately 0.8.

What clinical defect characterizes type 1 diabetes mellitus?

Autoimmune destruction of pancreatic β-cells leading to absolute insulin deficiency.

What is the primary defect in type 2 diabetes mellitus?

Insulin resistance in peripheral tissues, followed by compensatory hyperinsulinemia and eventual β-cell failure.

How does obesity promote insulin resistance?

By increasing adipose tissue inflammation and releasing pro-inflammatory cytokines and free fatty acids.

List the tissue, compartment, and classification of glycogenesis.

Liver and muscle; cytosol; anabolic.

Identify the tissue and compartment for lipolysis.

Adipose tissue and muscle; cytosol; catabolic.

Which pathway operates in all tissues except red blood cells and where?

The TCA cycle in the mitochondrial matrix; it is amphibolic.

What enzyme converts acetyl-CoA to malonyl-CoA?

Acetyl-CoA carboxylase (ACC).

Which transporter does AMPK stimulate to enhance glucose uptake in muscle?

GLUT4.

Which fatty-acid transporter’s activity is increased by AMPK?

CD36.

What is the largest single source of NADPH for fatty acid synthesis in most tissues?

The pentose phosphate pathway (noted indirectly through malate → pyruvate conversion producing NADPH).

Which hormone can exhibit both anabolic and catabolic effects depending on context?

Growth hormone.

What is the effect of glucagon on hepatic gluconeogenesis?

It stimulates gluconeogenesis in the liver.

How does cortisol influence protein metabolism?

It promotes proteolysis in muscle to supply amino acids for hepatic gluconeogenesis.

Which hormone primarily stimulates ketogenesis during fasting?

Glucagon (with supportive roles from low insulin and high fatty acid supply).

Why do red blood cells produce lactate even in oxygen-rich conditions?

Because they lack mitochondria and rely solely on anaerobic glycolysis, converting pyruvate to lactate.

What is the approximate RQ of a mixed diet in a normal, well-fed individual?

About 0.85.

Where is hexokinase found and what are its features?

Most tissues, low Km (high affinity), low Vmax, not inhibited by G6P

In the fed state, what is the hormonal profile?

High insulin, low glucagon

What are the main fuel sources?

Dietary (exogenous) glucose, fatty acids from chylomicrons/VLDL, amino acids from diet

Key processes in fed state?

Glycogenesis, glycolysis, lipogenesis, protein synthesis

What is the hormonal profile of the post-absorptive state (3-18 hours)?

Decreased insulin, increased glucagon

What is the primary glucose source during the post-absorptive state?

hepatic glycogenolysis

What are other contributors to blood glucose during the post-absorptive state?

gluconeogenesis from lactate (Cori Cycle), alanine (glucose-alanine cycle), glycerol

What is the main glucose source during the fasting state?

Gluconeogenesis (amino acids, glycerol, lactate)

Additional fuel adaptations during the fasting state?

Ketogenesis from fatty acid oxidation, increased lipolysis

Main adaptation goal during the starvation state?

Spare proteins to preserve vital functions

How does the fuel shift during the starvation state?

The brain uses more ketone bodies, glucose use decreases, and lipolysis provides the most energy

Which hormone is the master anabolic regulator?

Insulin

Which hormones are the main catabolic regulators?

Glucagon, epinephrine, and cortisol

Which hormone can be anabolic or catabolic?

Growth hormone

Effect of insulin on glycogenesis?

Increases in liver and skeletal muscle

Effect of glucagon on glycogenolysis?

Increases in liver

Effect of epinephrine on lipolysis?

Increased in adipose and muscle

What are the three main components of TEE?

Basal metabolic rate, thermic effect of food, physical activity

Largest contributor to TEE?

BMR (50-70%)

Which macronutrient has the highest thermic effect of food?

Protein (20-30%)

What is the respiratory quotient for carbohydrate oxidation?

1.0

RQ for fat oxidation?

~0.8

What does an RQ approaching 1 indicate?

More carbohydrate being oxidized

Main defect in type 1 diabetes?

Autoimmune destruction of pancreatic beta cells leading to a lack of insulin

Main defect in type 2 diabetes?

Insulin resistance in peripheral tissues leading to compensatory hyperinsulinemia leading to beta cell failure

How does obesity promote insulin resistance?

Increased adipose tissue inflammation, release of pro-inflammatory cytokines and free fatty acids