by: lim ju boo
This is a short refresher course in biochemistry (Part 1 and Part 2) for undergraduate and postgraduate students in biochemistry, nutrition, biochemical sciences, medical doctors, and other interested readers with some background in biological sciences and medicine.
Part 1:
1. What Is Biochemistry?
Biochemistry is the study of chemical processes in living organisms. It explains how molecules interact to sustain life, focusing on:
1. Metabolism (energy production & biomolecules).
2. Molecular biology (DNA, RNA, protein synthesis).
3. Enzymes & hormones (chemical messengers).
4. Medical applications (diseases, diagnostics, drug action).
5. Nutrition & metabolism (digestion, vitamins, diet).
Biochemistry bridges chemistry and biology and is essential for medicine, nutrition, genetics, and pharmacology.
2. The 4 Major Biomolecules
a) Carbohydrates (Sugars & Energy)
Function: Provide energy (ATP), store energy, structural support.
Examples:
Glucose (C₆H₁₂O₆) – Main energy source.
Glycogen – Energy storage in liver & muscles.
Cellulose – Plant fiber, aids digestion.
Metabolism:
Glucose+O2→ATP+CO2+H2OGlucose+O2→ATP+CO2+H2O
Carbohydrates are broken down in glycolysis to form ATP for cellular energy.
Medical Relevance:
Diabetes – Imbalance in glucose metabolism (insulin resistance).
Lactose intolerance – Inability to digest lactose due to lactase deficiency.
b) Proteins (Building Blocks of Life)
Function: Enzymes, hormones, immune response, muscle structure.
Made of: Amino acids (20 types).
Examples:
Hemoglobin – Carries oxygen in blood.
Insulin – Regulates blood sugar.
Enzymes – Speed up biochemical reactions.
Protein Metabolism:
Proteins → Amino acids → Energy or new proteins.
Excess proteins → Broken down into urea (excreted in urine).
Medical Relevance:
Kwashiorkor – Protein deficiency leads to swelling (edema).
Sickle cell anemia – Mutation in hemoglobin protein.
Enzyme deficiencies – Cause metabolic disorders (e.g., PKU).
c) Lipids (Fats & Membranes)
Function: Energy storage, cell membranes, hormone production.
Examples:
Triglycerides – Energy storage in fat cells.
Phospholipids – Form cell membranes.
Cholesterol – Needed for vitamin D & steroid hormones.
Lipid Metabolism:
Fats+O2→ATP+CO2+H2OFats+O2→ATP+CO2+H2O
Fat is broken down for energy during fasting or exercise.
Medical Relevance:
Obesity & heart disease – Excess fats lead to arterial blockages.
Ketosis – Fat breakdown produces ketones (useful in fasting & diabetes).
Omega-3 fatty acids – Reduce inflammation & support brain health.
d) Nucleic Acids (DNA & RNA – The Blueprint of Life)
Function: Store & transmit genetic information.
Examples:
DNA (Deoxyribonucleic Acid) – Stores genetic code.
RNA (Ribonucleic Acid) – Helps in protein synthesis.
DNA Replication & Protein Synthesis:
DNA → RNA (Transcription).
RNA → Protein (Translation).
Medical Relevance:
Genetic disorders (e.g., cystic fibrosis, Down syndrome).
Cancer – Mutations in DNA lead to uncontrolled cell growth.
mRNA vaccines – Used in COVID-19 to trigger immune response.
Enzymes: The Biological Catalysts:
Function: Speed up chemical reactions in the body.
Example: Amylase (digests starch into glucose).
Enzyme Characteristics
Highly specific – Act on specific substrates.
Work best at optimal temperature & pH.
Can be regulated by inhibitors (drugs or toxins).
Medical Relevance:
Liver enzymes – Used to diagnose liver diseases.
Enzyme inhibitors – Used as drugs (e.g., aspirin inhibits pain enzymes).
Metabolism:
Metabolism & Energy Production (ATP – The Energy Currency)
Metabolism: The sum of all chemical reactions in the body.
ATP Production Pathways
1. Glycolysis (Breaks down glucose → ATP).
2. Krebs Cycle (Converts fats, proteins, and sugars → ATP).
3. Electron Transport Chain (Most ATP produced).
Glucose+O2→CO2+H2O+38ATPGlucose+O2→CO2+H2O+38ATP
Medical Relevance:
Mitochondrial diseases – Affect ATP production, causing fatigue.
Metabolic disorders – Diabetes, obesity, and thyroid diseases..
Biochemistry of Nutrition & Vitamins:
Macronutrients (Carbohydrates, Proteins, Fats):
Provide energy & building materials.
Imbalances cause malnutrition, obesity, or metabolic diseases.
Micronutrients (Vitamins & Minerals)
Vitamin Functions & Deficiency Diseases:
Vitamin A Vision, immune function , night blindness. Vitamin B₁₂ red blood cells, anemia, nerve damage, vitamin C - collagen, immunity, scurvy; Vitamin D - bone health, rickets; Vitamin K, blood clotting, excess bleeding
Medical Relevance:
Nutritional deficiencies cause disease (e.g., scurvy, anemia).
Balanced diet prevents chronic diseases.
Hormones & Biochemistry of Disease:
Key Hormones:
Hormone function - Produced by insulin, lowers blood sugar; pancreas glucagon - raises blood sugar thyroxine controls metabolism. Thyroid cortisol; stress hormones in adrenal glands; testosterone / estrogen - reproductive hormones and gonads
Medical Relevance:
Diabetes – Insulin imbalance.
Hypothyroidism – Low thyroxine slows metabolism.
Stress disorders – High cortisol affects immunity.
That partially completes our Biochemistry refresher!
I hope biochemical and medical students including medical doctors can now have a solid understanding of:
1. Biomolecules & metabolism
2. Enzymes & ATP production
3. Nutritional biochemistry
4. Medical applications of biochemistry
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Part II
Let's now continue to talk a litter bit more on nutritional biochemistry useful to nutritionists and dieticians pertaining to:
Inborn Errors of Metabolism (IEMs) – A Medical Biochemistry Perspective
Let’s delve into inborn errors of metabolism (IEMs) from a medical and clinical perspective. These are genetic disorders affecting biochemical pathways, often leading to toxic accumulation or deficiency of essential compounds.
1. What Are Inborn Errors of Metabolism (IEMs)?
Definition: IEMs are hereditary metabolic disorders caused by enzyme defects in biochemical pathways. They are often autosomal recessive and can lead to:
1. Toxic metabolite buildup (e.g., phenylalanine in PKU).
2. Deficiency of essential molecules (e.g., energy production defects in mitochondrial disorders).
Most IEMs involve defects in:
Carbohydrate metabolism.
Amino acid metabolism.
Lipid metabolism.
Nucleotide metabolism.
Energy metabolism (mitochondrial disorders).
Lysosomal storage diseases.
Categories & Examples of IEMs
a). Carbohydrate Metabolism Disorders
Problem: Enzyme deficiencies in glycolysis, gluconeogenesis, or glycogen storage lead to hypoglycemia, acidosis, or storage issues.
Glycogen Storage Diseases (GSDs)
Type Deficient Enzyme Effect GSD I (Von Gierke’s disease), Glucose-6-phosphatase . Severe fasting hypoglycemia, hepatomegaly GSD V (McArdle’s disease), Muscle phosphorylase, Muscle cramps, exercise intolerance
Galactosemia
Deficient enzyme: Galactose-1-phosphate uridyl transferase (GALT).
Effect: Accumulation of galactose-1-phosphate causes jaundice, hepatomegaly, cataracts in infants.
Treatment: Galactose-free diet (avoid milk).
b). Amino Acid Metabolism Disorders
Problem: Defective enzymes in amino acid breakdown lead to toxic accumulation.
Phenylketonuria (PKU)
Deficient enzyme: Phenylalanine hydroxylase.
Effect: Accumulation of phenylalanine leads to intellectual disability, seizures, musty urine odor.
Treatment: Low-phenylalanine diet (avoid aspartame).
Alkaptonuria
Deficient enzyme: Homogentisate oxidase.
Effect: Dark urine (black on standing), arthritis, ochronosis (dark cartilage pigmentation).
Treatment: Vitamin C & diet restriction of tyrosine and phenylalanine.
Maple Syrup Urine Disease (MSUD)
Deficient enzyme: Branched-chain ketoacid dehydrogenase (BCAA metabolism).
Effect: Accumulation of leucine, isoleucine, and valine causes urine that smells like maple syrup, severe CNS damage.
Treatment: Dietary restriction of BCAAs.
c). Lipid Metabolism Disorders
Problem: Defective fatty acid oxidation leads to hypoglycemia and organ dysfunction.
Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)
Deficient enzyme: MCAD enzyme (fatty acid oxidation defect).
Effect: Hypoglycemia, lethargy, coma during fasting.
Treatment: Avoid fasting, high-carbohydrate diet.
Hyperlipoproteinemias:
Defective lipid transport proteins cause high cholesterol, cardiovascular risks.
Example: Familial hypercholesterolemia (LDL receptor defect) → early atherosclerosis.
Biochemical Lysosomal Storage Diseases (LSDs):
Lysosomal Storage Diseases (LSDs) are a group of rare inherited metabolic disorders that occur when lysosomes, the cellular organelles responsible for breaking down various substances, fail to function properly. Lysosomes contain enzymes that break down complex molecules, such as proteins, lipids, and carbohydrates. When any of these enzymes are defective or missing, the specific substrate that the enzyme normally breaks down accumulates within the lysosome. This accumulation of undigested macromolecules leads to cellular dysfunction, which ultimately damages tissues and organs over time.
Key Aspects of LSDs:
1. Defective Lysosomal Enzymes: The core problem in LSDs is the lack of specific lysosomal enzymes, which results in the inability to break down complex molecules. These defective enzymes are often the result of mutations in genes that encode them.
2. Accumulation of Substrates: When the enzymes don’t work, the macromolecules that should be broken down (e.g., lipids, carbohydrates, proteins) accumulate within lysosomes. This causes a buildup of these materials inside cells, disrupting their normal function and leading to cellular damage.
3. Symptoms and Organ Damage: The accumulation of these macromolecules often affects several organs, including the liver, spleen, heart, and brain. The symptoms vary depending on which molecules accumulate and which organs are most affected. Common symptoms include developmental delay, organ enlargement, bone abnormalities, and neurological problems.
Types of Lysosomal Storage Diseases:
There are more than 50 types of LSDs, each associated with a different enzyme deficiency. Some well-known LSDs include:
1. Gaucher Disease: Caused by a deficiency in the enzyme glucocerebrosidase, leading to the accumulation of glucocerebroside in macrophages, which causes organ enlargement and skeletal issues.
2. Tay-Sachs Disease: Caused by a deficiency in hexosaminidase A, resulting in the accumulation of GM2 gangliosides in nerve cells, leading to neurodegeneration.
3. Fabry Disease: Caused by a deficiency in alpha-galactosidase A, leading to the accumulation of globotriaosylceramide in blood vessels and various organs, causing pain, kidney damage, and heart issues.
3. Hunter Syndrome: Caused by a deficiency in iduronate-2-sulfatase, leading to the accumulation of glycosaminoglycans (GAGs) and affecting the development of bones, heart, and central nervous system.
Challenges in LSDs:
1. Progressive Nature: Many LSDs cause progressive damage, especially to the nervous system, leading to severe physical and cognitive decline.
2. Diagnosis: LSDs are often diagnosed late in life because symptoms can be vague at first, and they may not appear until the disease has already caused significant damage.
3. Treatment: While there is no cure for most LSDs, there are some treatment options available, such as enzyme replacement therapy (ERT) and substrate reduction therapy, which can help manage the disease by supplementing the missing enzyme or reducing the buildup of substrates.
LSDs are a vivid reminder of how delicate our biochemical systems are, and the importance of enzymes in maintaining cellular health and function.
Treatment: Enzyme replacement therapy (ERT) is available for Gaucher’s, Fabry’s, and Pompe’s disease.
Energy Metabolism Disorders (Mitochondrial Diseases):
Problem: Defective mitochondria impair ATP production, affecting organs with high energy demand (brain, muscle).
Leigh Syndrome
Defective enzyme: Pyruvate dehydrogenase.
Effect: Lactic acidosis, progressive neurodegeneration.
MELAS Syndrome (Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like Episodes)
Defective mitochondrial DNA mutations.
Effect: Muscle weakness, stroke-like episodes.
Diagnosis of IEMs
Newborn Screening (Guthrie Test, Mass Spectrometry)
Blood spot tests detect PKU, MCADD, Galactosemia, MSUD.
Early detection prevents severe outcomes.
Biochemical Tests
Blood ammonia, lactate – High in urea cycle & mitochondrial disorders.
Urine organic acids – Diagnoses MSUD, PKU, and others.
Genetic Testing
Identifies specific mutations in enzyme genes.
Treatment Strategies for IEMs:
Dietary Modifications
PKU → Low-phenylalanine diet.
Galactosemia → Avoid dairy.
MSUD → Restrict BCAAs.
Enzyme Replacement Therapy (ERT)
Used for Gaucher’s, Fabry’s, Pompe’s diseases.
Gene Therapy (Emerging Treatment)
Future potential in mitochondrial diseases & enzyme defects.
Avoiding Catabolic Stress
MCADD & mitochondrial disorders → Avoid fasting, high-carb intake.
Liver Transplant (Severe Cases)
Used in urea cycle disorders & severe metabolic diseases.
Clinical Perspective
1. IEMs are genetic metabolic disorders affecting enzyme function.
2. Early diagnosis (newborn screening) is crucial for preventing complications.
3. Dietary modifications, enzyme replacement, and emerging gene therapy offer treatments.
4. Research is ongoing to find advanced therapies (CRISPR gene editing, metabolic engineering).
Let us now go a very little bit on:
Metabolic Pathways and Cellular Signaling – A Biochemical Perspective
Since by now readers already have some idea in medical biochemistry, let's go deeper into the types of metabolic pathways and cellular signaling mechanisms, focusing on their medical relevance.
1. Metabolic Pathways
Metabolism consists of highly coordinated anabolic (biosynthetic) and catabolic (breakdown) pathways that regulate energy and biomolecule production.
A. Catabolic Pathways (Breakdown Pathways)
Purpose: Break down complex molecules to release energy (ATP) and provide building blocks for biosynthesis.
Glycolysis (Glucose Breakdown)
Location: Cytoplasm.
Key steps:
1. Glucose → Pyruvate (via hexokinase, phosphofructokinase (PFK-1)).
ATP production (substrate-level phosphorylation).
Fate of Pyruvate:
Aerobic: Converted to Acetyl-CoA → enters TCA cycle.
Anaerobic: Converted to lactate (in RBCs, muscles).
Clinical Relevance: Pyruvate kinase deficiency → hemolytic anemia (RBCs lack ATP).
2. Citric Acid Cycle (Krebs/TCA Cycle)
Location: Mitochondrial matrix.
Function: Generates NADH, FADH₂, and GTP from Acetyl-CoA.
Clinical Relevance: Thiamine (B1) deficiency → Beriberi, Wernicke-Korsakoff syndrome (PDH complex dysfunction).
3. Electron Transport Chain (Oxidative Phosphorylation)
Location: Inner mitochondrial membrane.
Function: Uses NADH & FADH₂ to generate ATP via ATP synthase.
Clinical Relevance: Cyanide poisoning inhibits complex IV, leading to tissue hypoxia.
4. Beta-Oxidation (Fatty Acid Breakdown)
Location: Mitochondria.
Function: Breaks down fatty acids to Acetyl-CoA → enters TCA cycle.
Clinical Relevance: MCAD deficiency → hypoglycemia, sudden infant death syndrome (SIDS).
5. Pentose Phosphate Pathway (PPP)
Location: Cytoplasm.
Function: Produces NADPH (for biosynthesis) & Ribose-5-phosphate (for nucleotides).
Clinical Relevance: G6PD deficiency → hemolysis in oxidative stress (favism).
Anabolic Pathways (Biosynthetic Pathways):
Purpose: Build complex molecules from simple precursors.
1. Gluconeogenesis (Glucose Synthesis)
Location: Liver & kidneys.
Function: Converts non-carbohydrate sources (lactate, amino acids, glycerol) into glucose.
Clinical Relevance: Defects lead to fasting hypoglycemia.
2. Fatty Acid Synthesis
Location: Liver, adipose tissue (cytoplasm).
Function: Converts Acetyl-CoA → Fatty Acids.
Regulation: Activated by insulin.
Clinical Relevance: Excess leads to fatty liver disease.
3. Cholesterol Synthesis
Location: Liver (cytoplasm).
Key step: HMG-CoA reductase converts Acetyl-CoA to cholesterol.
Clinical Relevance: Statins inhibit HMG-CoA reductase to lower LDL cholesterol.
4. Amino Acid & Nucleotide Biosynthesis
Amino acids: Essential for proteins, neurotransmitters (e.g., serotonin from tryptophan).
Nucleotides: Required for DNA/RNA synthesis (Purine & Pyrimidine pathways).
Clinical Relevance: Defects cause metabolic disorders (e.g., Lesch-Nyhan syndrome – HGPRT deficiency, causing excess uric acid).
Let's now go a little bit on Cellular Signaling Pathways
Cells communicate via biochemical signaling pathways to regulate metabolism, immunity, growth, and responses to stress.
A. Types of Cell Signaling
B. Major Cellular Signaling Pathways
Key Mechanisms: Receptors → Secondary Messengers → Cellular Response
1. G-Protein Coupled Receptors (GPCRs)
Example: β-adrenergic receptor (epinephrine).
Second messenger: cAMP (activates PKA).
Clinical Relevance: GPCR mutations → hormonal disorders, cancers.
2. Receptor Tyrosine Kinase (RTK)
Example: Insulin receptor, Growth factors (EGFR).
Pathway: RAS-MAPK & PI3K-AKT.
Clinical Relevance: Mutations → cancers (EGFR in lung cancer, HER2 in breast cancer).
3. JAK-STAT Pathway (Cytokine Signaling)
Example: Interferons, Erythropoietin.
Function: Activates immune responses & hematopoiesis.
Clinical Relevance: Defects → SCID (severe combined immunodeficiency).
4. mTOR Pathway (Cell Growth & Metabolism)
Function: Regulates cell growth, protein synthesis.
Clinical Relevance: Hyperactivation → cancer, metabolic disorders.
5. β-Catenin Pathway
Function: Controls cell proliferation & embryonic development.
Clinical Relevance: Overactivation → colorectal cancer.
6. NF-κB Pathway (Inflammation & Immunity)
Function: Regulates inflammation, immune responses.
Clinical Relevance: Chronic activation → autoimmune diseases, cancer.
Integration of Metabolic & Signaling Pathways in Medicine
1. Diabetes: Insulin signaling defects → dysregulated glucose metabolism.
2. Cancer: Oncogenic signaling (e.g., RTK mutations) → uncontrolled growth.
3. Neurodegeneration: Defective mitochondrial metabolism (e.g., Parkinson’s, Alzheimer’s).
4. Obesity & Metabolic Syndrome: Dysregulation of lipid metabolism & mTOR signaling.
Summary:
Metabolism and signaling are deeply interconnected – nutrient availability affects cell signaling, and signaling pathways regulate metabolic homeostasis.
Understanding these mechanisms helps in diagnosing & treating metabolic diseases.
I hope this is an easy to understand summary in biochemistry for nutritionists, medical doctors and clinical scientists
