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BI13.1-5 | Miscellaneous — Part 2

HIV and the Biochemical Changes in AIDS

You learned in NCERT that HIV (Human Immunodeficiency Virus) attacks the immune system. Now let's understand the biochemistry behind this.

Figure: HIV and the Biochemical Changes in AIDS

HIV is a retrovirus — it carries its genetic material as RNA, not DNA. The key enzyme that makes HIV unique is reverse transcriptase, which converts viral RNA into DNA (the reverse of the normal Central Dogma: DNA → RNA → Protein). This viral DNA then integrates into the host cell's genome using another enzyme called integrase.

The virus specifically targets CD4+ T-helper cells because the HIV envelope protein gp120 binds to the CD4 receptor on these cells — like a specific key fitting a lock.

The life cycle of HIV involves these biochemical steps:
1. Attachment — gp120 binds to CD4 and a co-receptor (CCR5 or CXCR4)
2. Fusion and entry — the viral membrane fuses with the host cell
3. Reverse transcription — reverse transcriptase converts RNA → DNA
4. Integration — integrase inserts viral DNA into the host genome
5. Replication — the host cell's own machinery makes new viral RNA and proteins
6. Assembly and budding — new virus particles are assembled and released
7. Maturation — viral protease cleaves precursor proteins into functional forms

As HIV destroys CD4+ cells over years, the immune system collapses, leading to AIDS. The biochemical changes in AIDS include:

• Immunological: CD4 count drops below 200 cells/μL (normal: 500-1500)
• Metabolic: Wasting syndrome with increased protein catabolism and negative nitrogen balance
• Lipid abnormalities: Hypertriglyceridaemia and low HDL cholesterol (worsened by some antiretroviral drugs)
• Oxidative stress: Increased free radical production with depleted antioxidant defences (low glutathione)

Every class of anti-HIV drug targets one of these biochemical steps: NRTIs and NNRTIs block reverse transcriptase, protease inhibitors block viral maturation, and integrase inhibitors prevent viral DNA insertion.

Metabolism of Alcohol — What Happens After a Drink

When a person consumes alcohol (ethanol), the liver does most of the work to break it down. Understanding this pathway explains why chronic drinking damages the liver.

Figure: Metabolism of Alcohol — What Happens After a Drink

Ethanol metabolism occurs primarily in the liver through three pathways:

1. Alcohol Dehydrogenase (ADH) Pathway — the main route:
• Ethanol → Acetaldehyde (by alcohol dehydrogenase, using NAD+ → NADH)
• Acetaldehyde → Acetate (by aldehyde dehydrogenase, again using NAD+ → NADH)
• Acetate → Acetyl-CoA → enters the citric acid cycle or is used for fatty acid synthesis

2. Microsomal Ethanol Oxidising System (MEOS):
• Uses cytochrome P450 (CYP2E1) — becomes important in chronic drinkers because it is inducible (the more you drink, the more of this enzyme the liver makes)
• This is why chronic drinkers "tolerate" more alcohol — they metabolise it faster through MEOS

3. Catalase Pathway:
• Minor role; uses hydrogen peroxide (H₂O₂)

The critical biochemical consequence is a massive shift in the NAD+/NADH ratio. Alcohol metabolism floods the cell with NADH, which disrupts multiple pathways:

• Fatty liver (steatosis): Excess NADH inhibits fatty acid oxidation → fat accumulates in liver cells. Think of it as the liver becoming "too busy" processing alcohol to burn fat
• Hypoglycaemia: NADH inhibits gluconeogenesis → fasting blood sugar drops dangerously (this is why alcoholics can have life-threatening low blood sugar)
• Lactic acidosis: Excess NADH converts pyruvate to lactate → metabolic acidosis
• Hyperuricaemia: Lactate competes with uric acid for excretion → gout risk increases

Effects of Chronic Alcoholism

Chronic alcohol consumption causes progressive liver damage through three stages:

Figure: Effects of Chronic Alcoholism

1. Fatty liver (steatosis) — reversible if alcohol is stopped; fat droplets accumulate in hepatocytes
2. Alcoholic hepatitis — inflammation with hepatocyte necrosis; acetaldehyde is the main toxic culprit — it forms protein adducts, triggers immune responses, and generates free radicals
3. Cirrhosis — irreversible scarring (fibrosis) replacing normal liver tissue; leads to liver failure

Beyond the liver, chronic alcoholism affects:

• Brain: Thiamine (Vitamin B1) deficiency → Wernicke-Korsakoff syndrome (confusion, memory loss, eye movement problems). Alcohol impairs thiamine absorption and utilisation
• Pancreas: Chronic pancreatitis with impaired insulin secretion
• Blood: Megaloblastic anaemia (folate deficiency), sideroblastic anaemia (impaired haem synthesis)
• Heart: Alcoholic cardiomyopathy — direct toxic effect of acetaldehyde on cardiac muscle

A helpful mnemonic for the metabolic effects of alcohol:
FALL-HUG — Fatty liver, Acidosis (lactic), Low glucose (hypoglycaemia), Lactate elevation, Hyperuricaemia, Urea cycle disruption, Gout risk