Review of Key Concepts in Metabolism

ATP Production Pathways

Ketosis

• An alternative pathway to produce ATP without using glucose or carbohydrates.

• Involves burning fats and utilizing them as keto.

Carbohydrate Metabolism (Glycolysis)

• Glucose is broken down into pyruvate, then pyruvate into acetyl CoA, which enters the TCA cycle.

Fatty Acid Metabolism

• Fatty acids (lipids) can convert to bioesters, similar to pyruvate.

• Fatty acids convert to acetyl CoA but do not go through the TCA cycle.

Amino Acid Metabolism

• Amino acids are the building blocks of proteins.

• Excess amino acids are not stored in the body, necessitating daily protein intake.

• Excess amino acids are excreted, primarily in the urine as urea.

• Urea is produced via the urea cycle.

Proteinuria

• Protein in the urine is abnormal and known as proteinuria.

• It can indicate nephrotic or nephritic syndrome.

• Proteins, being large molecules, should not filter through the kidneys; their presence indicates kidney damage.

• Diabetes can cause kidney damage by glycosylating the glomerulus walls.

• Proteinuria presents as frothy, bubbly urine.

Urea Cycle

• The amino group from amino acids converts to urea, which is excreted in the urine.

• Urea is toxic, necessitating its excretion.

• Kidney failure leads to urea buildup, causing encephalopathy, requiring dialysis.

• Dialysis involves cleaning the blood via a machine.

• Kidney failure is irreversible; the only solution is a kidney transplant.

Kidney Function

• The functional unit of the kidney is the glomerulus, located within nephrons.

• Each kidney contains approximately 1,000,000 nephrons.

• Nephrons die over time, with GFR decreasing with age.

• Kidney failure occurs when less than 30% of nephrons are viable.

Enzymes

• Enzymes are usually recognized by the suffix "-ase".

• Reactions in the body are driven by enzymatic reactions.

• Kinase enzymes transfer phosphate groups (important in ATP production).

Glycolysis

• Two NADH molecules generate four ATP molecules.

Alternative Metabolic Pathways

Fructose

• Fructose is a disaccharide found in sucrose, sugar, and fruits.

• Fructose is metabolized more quickly than glucose.

• It can be converted to fructose-6-phosphate, entering the glycolysis cycle.

Galactose

• Galactose is found in milk (lactose).

• It is converted to glucose-6-phosphate.

• Galactosemia: A condition where individuals lack the enzyme to digest galactose, leading to a buildup of galactose in the body.

• Galactosemia is a metabolic issue, not just a GI issue like lactose intolerance.

• Galactose buildup can cause cataracts, vascular problems, and neurological issues.

• Treatment involves avoiding foods containing galactose.

Mannose

• Mannose is found in fruits like cranberries and currants.

• Mannose is closely related to fructose.

• It can metabolize into pyruvate and works similarly to glucose.

Pyruvate Metabolism

• Pyruvate can convert into acetyl CoA (aerobic conditions) or lactate (anaerobic conditions).

Lactate

• Lactate is produced under anaerobic conditions.

• Lactic acid buildup in muscles causes soreness after intense workouts.

• It takes about three days for lactate to be cleared.

Ethanol

• Ethanol production occurs via fermentation in microorganisms, not in humans.

Clinical Relevance of Lactate

• Blood lactate levels are clinically relevant.

• Lactate levels increase when muscle needs reoxidation.

• During a heart attack, low oxygen perfusion causes muscle death, increasing lactic acid levels.

• Lactate is a sensitive but nonspecific marker for oxygen deprivation.

• Elevated lactate levels can indicate various conditions, including COPD and infections.

• Extremely high lactate levels can indicate rhabdomyolysis.

Heart Attack

• A blood clot in coronary vessels leads to a heart attack.

• Anything distal to the clot dies due to lack of perfusion, converting to lactate.

ATP Yield

• ATP is required to produce more ATP.

Blood Glucose Level

• Blood glucose level refers to the amount of glucose in the blood.

• Glucose is supposed to move to the cells and not stay in the blood.

• Normal blood glucose levels range from 80 to 120 (fasting).

• High blood glucose levels can indicate insulin problems.

• Insulin drives glucose into cells.

• Excess glucose is stored as glycogen in the liver through glucagon stimulation.

• Glucagon is a hormone from the pancreas and is inversely proportionate to insulin.

• Stored glucose can also be stored as fats.