Core Concepts in Biochemistry: Metabolism, Genetics, and Disorders

Posted on Oct 4, 2025 in Biology

Proteins: Structure and Function

Proteins are complex molecules made up of amino acids. They perform various functions in the body, such as:

  1. Structural support (e.g., collagen)
  2. Enzymatic activity (e.g., lactase)
  3. Transport (e.g., hemoglobin)
  4. Defense (e.g., antibodies)

Classification of Proteins

  1. Based on Structure:
    • Fibrous proteins (e.g., collagen)
    • Globular proteins (e.g., enzymes, antibodies)
  2. Based on Function:
    • Enzymes
    • Hormones
    • Structural proteins
    • Transport proteins
    • Defense proteins

The Urea Cycle

The urea cycle is a series of biochemical reactions that occur in the liver to remove excess ammonia from the body. The key reactions involve:

  1. Ammonia Conversion: Ammonia is converted into urea through a series of enzyme-catalyzed reactions.
  2. Key Enzymes:
    • Carbamoyl phosphate synthetase I
    • Ornithine transcarbamylase
    • Argininosuccinate synthetase
    • Argininosuccinase
    • Arginase

Disorders of the Urea Cycle

  1. Urea Cycle Disorders: Genetic defects in enzymes involved in the urea cycle, leading to ammonia accumulation in the blood.
  2. Symptoms:
    • Vomiting
    • Lethargy
    • Seizures
    • Developmental delays

Treatment often involves dietary restrictions and medications to manage ammonia levels.

Lipids and Their Biological Roles

Lipids are biomolecules that include fats, oils, phospholipids, and steroids. They play crucial roles in:

  1. Energy storage
  2. Cell membrane structure
  3. Hormone production
  4. Insulation and protection

Ketogenesis: Producing Ketone Bodies

Ketogenesis is a metabolic process that occurs in the liver when glucose is low. It produces ketone bodies from fatty acids. Here’s how it works:

  1. Low Glucose Levels: When glucose is scarce, the liver breaks down fat for energy.
  2. Fatty Acid Breakdown: Fatty acids are converted into acetyl-CoA.
  3. Ketone Body Production: Acetyl-CoA is then converted into three types of ketone bodies:
    • Acetoacetate
    • Beta-hydroxybutyrate
    • Acetone

Ketone bodies are an alternative energy source for the brain, heart, and other organs.

Disorders of Lipid Metabolism

  1. Hyperlipidemia: High levels of lipids in the blood, increasing cardiovascular risk.
  2. Familial Hypercholesterolemia: Genetic disorder causing high cholesterol.
  3. Lipid Storage Diseases: Disorders like Gaucher’s disease, where lipids accumulate in cells.
  4. Ketosis: Excessive ketone production, often seen in diabetes or low-carb diets.

These disorders can lead to serious health issues, such as cardiovascular disease and organ damage.

Glycolysis: Glucose to Pyruvate Conversion

Glycolysis is a metabolic pathway that converts glucose into pyruvate, producing energy in the form of ATP and NADH. It occurs in the cytoplasm of cells and is a crucial step in cellular respiration.

Pathway of Glycolysis

  1. Glucose Phosphorylation: Glucose is converted into glucose-6-phosphate (G6P) using 1 ATP.
  2. Conversion to Fructose-6-phosphate: G6P is converted into fructose-6-phosphate (F6P).
  3. Phosphorylation: F6P is converted into fructose-1,6-bisphosphate (F1,6BP) using 1 ATP.
  4. Splitting: F1,6BP is split into two molecules: glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP).
  5. Pyruvate Production: G3P is converted into pyruvate, generating 4 ATP and 2 NADH molecules.

Energy Production

Glycolysis produces a net gain of 2 ATP and 2 NADH molecules per glucose molecule.

Glycogen Storage Diseases (GSD)

Glycogen storage diseases are a group of genetic disorders that affect the storage and breakdown of glycogen, a complex carbohydrate stored in the liver and muscles. Some common types include:

  • Type I (Von Gierke’s Disease): Deficiency of glucose-6-phosphatase, leading to glycogen accumulation in the liver.
  • Type II (Pompe Disease): Deficiency of acid alpha-glucosidase, leading to glycogen accumulation in muscles.

Symptoms include hypoglycemia, fatigue, and muscle weakness. Treatment often involves dietary management and enzyme replacement therapy.

Gluconeogenesis: Generating Glucose

Gluconeogenesis is a metabolic pathway that generates glucose from non-carbohydrate sources like amino acids, lactate, and glycerol. The key reactions are:

  1. Pyruvate to Oxaloacetate: Pyruvate is converted to oxaloacetate via pyruvate carboxylase.
  2. Oxaloacetate to Phosphoenolpyruvate (PEP): Oxaloacetate is converted to PEP via PEP carboxykinase.
  3. Conversion to Fructose-1,6-bisphosphate: PEP is converted through several steps to fructose-1,6-bisphosphate.
  4. Fructose-1,6-bisphosphate to Fructose-6-phosphate: Fructose-1,6-bisphosphate is converted to fructose-6-phosphate via fructose-1,6-bisphosphatase.
  5. Glucose-6-phosphate Production: Fructose-6-phosphate is converted to glucose-6-phosphate.
  6. Glucose Production: Glucose-6-phosphate is converted to glucose via glucose-6-phosphatase.

Gluconeogenesis is essential for maintaining blood glucose levels, especially during fasting or low-carb diets.

Electron Transport Chain (ETC)

The Electron Transport Chain is a series of protein complexes located in the mitochondrial inner membrane. It is the primary mechanism for generating ATP during oxidative phosphorylation.

Key Steps of the ETC

  1. Electron Transfer: Electrons from NADH and FADH2 are passed through a series of protein complexes.
  2. Proton Pumping: As electrons flow through the complexes, protons (H+ ions) are pumped across the membrane, creating a proton gradient.
  3. ATP Synthesis: The proton gradient drives ATP synthase to produce ATP from ADP and Pi.

Importance

The Electron Transport Chain is crucial for generating most of the ATP produced during cellular respiration, making it essential for energy production in cells.

Transamination

Transamination is a chemical reaction that transfers an amino group (–NH2) from an amino acid to a keto acid, resulting in the formation of a new amino acid and a new keto acid.

Key Points

  • Enzyme: Catalyzed by transaminase enzymes.
  • Importance: Essential for the synthesis of non-essential amino acids and nitrogen metabolism.

Transamination plays a vital role in amino acid metabolism and nitrogen balance in the body.

Enzymes and Co-enzymes

Enzymes are biological molecules, typically proteins, that significantly speed up the rate of virtually all chemical reactions that take place within cells. They are vital for life and serve as catalysts in the body’s various biochemical processes.

Co-enzymes

Co-enzymes are organic molecules that work in conjunction with enzymes to facilitate the enzyme’s action. They often act as carriers of specific functional groups or electrons.

IUB Classification of Enzymes

The International Union of Biochemistry (IUB) classifies enzymes into six main categories based on the type of reaction they catalyze:

  1. Oxidoreductases: Catalyze oxidation/reduction reactions.
    • Example: Lactate dehydrogenase
  2. Transferases: Catalyze the transfer of functional groups.
    • Example: Transaminases
  3. Hydrolases: Catalyze hydrolysis reactions.
    • Example: Lipase
  4. [Classification continues]

Diabetes Mellitus: Causes, Symptoms, and Management

Diabetes Mellitus is a chronic metabolic disorder characterized by high blood sugar levels due to:

  • Insulin deficiency (Type 1 diabetes) or
  • Insulin resistance (Type 2 diabetes)

Symptoms

  1. Increased thirst and urination
  2. Fatigue
  3. Blurred vision
  4. Slow healing of wounds

Complications

  1. Cardiovascular disease
  2. Kidney damage (nephropathy)
  3. Nerve damage (neuropathy)
  4. Vision loss (retinopathy)

Management

  1. Medications (oral or injectable)
  2. Lifestyle changes (diet, exercise)
  3. Insulin therapy (for Type 1 and some Type 2 cases)

Early diagnosis and proper management can help control symptoms and prevent complications.

Ketoacidosis: Metabolic Complication

Ketoacidosis is a serious metabolic complication that occurs when the body produces high levels of ketones, acidic substances that can poison the body. It is often associated with:

  • Diabetes: Diabetic ketoacidosis (DKA) occurs when insulin levels are too low, causing the body to break down fat for energy.
  • Fasting or Starvation: Prolonged fasting or starvation can lead to ketoacidosis.
  • Alcoholism: Alcoholic ketoacidosis can occur in individuals who consume large amounts of alcohol.

Formation of Ketone Bodies

Ketone bodies are formed in the liver when fatty acids are broken down for energy. The three main ketone bodies are:

  1. Acetoacetate
  2. Beta-hydroxybutyrate
  3. Acetone

The formation of ketone bodies occurs through the following steps:

  1. Fatty Acid Breakdown: Fatty acids are broken down into acetyl-CoA.
  2. Ketogenesis: Acetyl-CoA is converted into ketone bodies in the liver.
  3. Release into Bloodstream: Ketone bodies are released into the bloodstream, where they can be used as energy by the brain, heart, and other organs.

In normal circumstances, ketone bodies are a useful energy source. However, in excess, they can lead to ketoacidosis, a potentially life-threatening condition.

Enzyme Inhibition

Enzyme inhibition is a process where the activity of an enzyme is reduced or blocked by a molecule called an inhibitor. Inhibitors can be classified into two main types:

Main Types of Inhibitors

  1. Competitive Inhibitors: Compete with the substrate for binding to the active site of the enzyme.
  2. Non-competitive Inhibitors: Bind to a different site on the enzyme, altering its shape and reducing its activity.

Types of Inhibition

  1. Reversible Inhibition: The inhibitor binds to the enzyme in a reversible manner.
  2. Irreversible Inhibition: The inhibitor covalently binds to the enzyme, permanently disabling it.

Importance

Enzyme inhibition is a crucial regulatory mechanism in biological systems and is also exploited in the development of drugs and pesticides.

DNA Replication

DNA replication is the process by which a cell makes an exact copy of its DNA before cell division. This process is crucial for the transmission of genetic information from one generation of cells to the next.

Key Steps in DNA Replication

  1. Initiation: DNA replication begins at specific regions called origins of replication, where helicase unwinds the DNA double helix.
  2. Unwinding: DNA helicase continues to unwind the DNA, creating a replication fork.
  3. Synthesis: DNA polymerase reads the template strands and matches nucleotides to the base pairing rules (A-T and G-C), synthesizing new complementary DNA strands.
  4. Leading Strand: DNA is synthesized continuously in the 5′ to 3′ direction.
  5. Lagging Strand: DNA is synthesized in short, discontinuous segments called Okazaki fragments.
  6. Ligation: DNA ligase seals the gaps between Okazaki fragments, forming a continuous strand.

Importance

DNA replication ensures that each new cell receives a complete and accurate set of genetic instructions, allowing for the continuation of cellular functions and the transmission of genetic traits.

RNA Transcription

RNA transcription is the process of creating a complementary RNA molecule from a DNA template. The stages involved are:

  1. Initiation: RNA polymerase binds to the promoter region of the DNA, unwinding the DNA double helix.
  2. Elongation: RNA polymerase reads the DNA template and synthesizes a complementary RNA strand by adding nucleotides.
  3. Termination: RNA polymerase reaches a termination signal, releasing the RNA transcript and detaching from the DNA.

These stages result in the creation of a single-stranded RNA molecule that can be used for protein synthesis or other cellular processes.

Hyperuricemia and Gout

Hyperuricemia: Elevated levels of uric acid in the blood, which can lead to Gout.

Gout: A type of arthritis characterized by sudden, severe joint pain, swelling, and redness, often affecting the big toe. It is caused by the deposition of urate crystals in joints due to high uric acid levels.

Causes of Hyperuricemia

  1. Overproduction of uric acid
  2. Underexcretion of uric acid
  3. Dietary factors (e.g., purine-rich foods)

Symptoms of Gout

  1. Sudden, intense joint pain
  2. Swelling and redness
  3. Limited mobility

Treatment

  1. Medications to reduce uric acid levels
  2. Anti-inflammatory medications for pain relief
  3. Lifestyle changes (diet, hydration)

Managing hyperuricemia and gout involves a combination of medical treatment and lifestyle modifications.