Metabolic Pathways and Diabetes Quiz

Glycolysis

• Glucose breaks down into two molecules of pyruvate (3 carbon sugar)
• 2 ATP formed in step 10 and 2 NADH = the energy product
• 2 ATP are used in steps 1 and 3, replaced in step 7

Gluconeogenesis

• Synthesis of glucose from non-carbohydrate precursors
• Main function is to supply blood glucose when carbohydrates are deficient (fasting, starvation, or low-carb diet)
• If glycogen stores are depleted, liver cells synthesize glucose
• Brain relies on glucose (120g/day)
• Non-carbohydrate precursors: lactate, pyruvate, glucogenic amino acids, glycerol, and propionate

Glycogenesis

• Synthesis of glycogen from glucose

Glycogenolysis

• Breakdown of glycogen to glucose

Pentose Phosphate Pathway

• Conversion of glucose to the 5-carbon sugar phosphate

Diabetes Mellitus

• A group of metabolic diseases with elevated blood glucose levels
• Caused by defects in insulin secretion, insulin action, or both
• Types: Type 1, Type 2, Gestational, and others

Lipid Metabolism

• Lipids are from three sources: diet, stored in adipose tissue, synthesized in the liver
• When glucose is low, triglycerides can be converted into acetyl CoA and used to generate ATP
• Fats (triglycerides) are ingested as food or synthesized by adipocytes or hepatocytes
• The main lipids in foods are fats = triglycerides
• Pancreatic lipase partially hydrolyzes triglycerides to mono- and di-glycerides, glycerol, and free fatty acids
• This process – lipolysis – takes place in the cytoplasm

Lipolysis

• Glycerol directly enters the glycolysis pathway as dihydroxyacetone phosphate (DHAP)
• Lipids are an important energy source for the body
• Triglycerides provide twice the energy per unit mass compared to carbs and proteins
• 1 molecule of a 12-carbon fatty acid yields 78 ATP total energy vs. glucose’s 32 ATP

Lipogenesis

• When glucose levels are high, excess acetyl CoA generated by glycolysis is converted into fatty acids, triglycerides, cholesterol, steroids, and bile salts
• This process creates fat from acetyl CoA and occurs in the cytoplasm of adipocytes or hepatocytes
• Triglycerides and lipids are stored in adipose tissue until needed

General Metabolism of Amino Acids

• Dietary and body proteins are broken down into amino acids (catabolic reaction)
• In transamination reactions, the amino group is removed, producing the carbon skeleton (keto acid)
• The amino group is excreted as urea
• The carbon skeleton is used for synthesizing non-essential amino acids
• It is also used for gluconeogenesis or complete oxidation
• Amino acids are used for synthesis of body proteins (anabolic reaction)

Amino Acid Degradation

• 10-15% of amino acids are broken down to CO2 and H2O, and the free energy is harvested
• The rest enter the TCA cycle in one of two ways:
  • Glucogenic amino acids are degraded to pyruvate or other TCA intermediates that will become glucose
  • Ketogenic amino acids are degraded to acetyl-CoA or acetoacetate, which can be made into fatty acids or ketone bodies

Amino Acid Metabolism Disorders

• Phenylketonuria (PKU): Absence or deficiency in the hepatic enzyme phenylalanine hydroxylase (PAH)
• When PAH is deficient, phenylalanine (Phe) accumulates because it cannot be converted to tyrosine
• Symptoms: Small head, delayed mental and social skills, seizures, and a “musty odour” to sweat, skin, and urine due to Phe conversion to phenylacetate (a ketone)
• Other disorders: Alkaptonuria (black urine), Maple syrup urine disease

Nucleic Acid Metabolism

• Nucleotides are the building blocks of nucleic acids (DNA and RNA)

Nucleotide Metabolism

• Synthesis of Nucleotides:
  • De novo Synthesis: Nucleotides are synthesized new from simple precursor molecules
  • Salvage Pathway: Recycling bases and nucleosides formed during breakdown of nucleic acids

Metabolic Disorders: Nucleotide Metabolism

• Human diseases involving abnormalities in purine metabolism: Gout – painful form of arthritis
• Caused by excess uric acid in the blood and tissues

Lipid Metabolism

• Lipids are a major source of energy.
• Triglycerides yield more energy per unit mass than carbohydrates and proteins.
• 1 molecule of a 12-carbon fatty acid provides 78 ATP, while glucose provides 32 ATP.

Lipolysis

• Glycerol can be used to produce glucose.
• Glycerol directly enters the glycolysis pathway as dihydroxyacetone phosphate (DHAP).

Lipogenesis

• Excess acetyl CoA generated by glycolysis can be converted into fatty acids, triglycerides, cholesterol, steroids, and bile salts.
• This process occurs in the cytoplasm of adipocytes or hepatocytes.
• Triglycerides and lipids are stored in adipose tissue until needed.

Amino Acid Metabolism

• Dietary proteins and body proteins are broken down into amino acids (catabolic reaction).
• Amino group removal in transamination reactions produces a carbon skeleton (keto acid).
• The amino group is excreted as urea.
• The carbon skeleton is used for synthesizing non-essential amino acids, gluconeogenesis, and complete oxidation.
• Amino acids are also used for the synthesis of body proteins (anabolic reaction).

Amino Acid Degradation

• 10-15% of amino acids are broken down to CO2 and H2O, with free energy harvested.
• The rest enter the TCA cycle through two pathways:
  • Glucogenic amino acids are broken down into pyruvate or other TCA intermediates that ultimately become glucose.
  • Ketogenic amino acids are broken down into acetyl-CoA or acetoacetate, which can be used to make fatty acids or ketone bodies.

Amino Acid Metabolism Disorders

• Phenylketonuria (PKU) is caused by a deficiency or absence of the hepatic enzyme phenylalanine hydroxylase (PAH).
• When PAH is deficient, phenylalanine (Phe) accumulates due to its inability to convert into tyrosine.
• Symptoms include small head, delayed mental and social skills, seizures, and a "musty odour" to the baby's sweat, skin, and urine resulting from the conversion of Phe to phenylacetate (a ketone).

Nucleic Acid Metabolism

• Nucleotide synthesis occurs through two pathways:
  • De novo synthesis: Nucleotides are synthesized from simple precursor molecules.
  • Salvage pathway: Recycling bases and nucleosides formed during nucleic acid breakdown.

Metabolic Disorders: Nucleotide Metabolism

• Human diseases involving abnormalities in purine metabolism include Gout.
• It is a painful form of arthritis caused by excess uric acid in the blood and tissues.

Summary: Metabolic Pathways of Glucose

Study Check

• Match the following processes:

  1. Glycolysis
  2. Glycogenesis
  3. Glycogenolysis
  4. Gluconeogenesis

  A. The synthesis of glucose from non-carbohydrates B. The breakdown of glycogen into glucose C. The oxidation of glucose to two pyruvate D. The synthesis of glycogen from glucose

Solution

• 1. Glycolysis - C. The oxidation of glucose to two pyruvate
• 2. Glycogenesis - D. The synthesis of glycogen from glucose
• 3. Glycogenolysis - B. The breakdown of glycogen into glucose
• 4. Gluconeogenesis - A. The synthesis of glucose from non-carbohydrates