8.4 Integration of citric acid cycle with other metabolic pathways

The citric acid cycle is a metabolic hub, connecting various pathways in the body. It's not just about energy production - it's also a source of building blocks for important molecules. Understanding how it links to other processes helps us see the big picture of metabolism.

This section looks at how the cycle interacts with other pathways. We'll see how it provides materials for making glucose, fats, and proteins. We'll also learn about reactions that keep the cycle balanced and running smoothly.

Biosynthetic Pathways

Gluconeogenesis

Top images from around the web for Gluconeogenesis

• 

  Regulation of Cellular Respiration · Biology View original

  Is this image relevant?

• 

  Gluconeogenesis - Wikipedia View original

  Is this image relevant?

• 

  File:Glycolytic and gluconeogenic pathways.jpg - Wikimedia Commons View original

  Is this image relevant?

• 

  Regulation of Cellular Respiration · Biology View original

  Is this image relevant?

• 

  Gluconeogenesis - Wikipedia View original

  Is this image relevant?

1 of 3

Top images from around the web for Gluconeogenesis

• 

  Regulation of Cellular Respiration · Biology View original

  Is this image relevant?

• 

  Gluconeogenesis - Wikipedia View original

  Is this image relevant?

• 

  File:Glycolytic and gluconeogenic pathways.jpg - Wikimedia Commons View original

  Is this image relevant?

• 

  Regulation of Cellular Respiration · Biology View original

  Is this image relevant?

• 

  Gluconeogenesis - Wikipedia View original

  Is this image relevant?

1 of 3

• Gluconeogenesis is the synthesis of glucose from non-carbohydrate precursors (pyruvate, lactate, glycerol, amino acids)
• Occurs primarily in the liver and kidneys during periods of fasting or prolonged exercise
• Reverses many of the steps of glycolysis but uses different enzymes (phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase, glucose-6-phosphatase)
• Requires energy input from ATP and GTP to drive the endergonic reactions
• Maintains blood glucose levels during periods of fasting or prolonged exercise (hypoglycemia prevention)

Fatty Acid and Lipid Synthesis

• Fatty acid synthesis occurs in the cytosol and uses acetyl-CoA as a building block
• Acetyl-CoA carboxylase catalyzes the rate-limiting step, converting acetyl-CoA to malonyl-CoA
• Fatty acid synthase complex catalyzes the sequential addition of malonyl-CoA to a growing fatty acid chain
• NADPH provides reducing equivalents for the synthesis of fatty acids
• Triacylglycerols are synthesized from fatty acids and glycerol-3-phosphate in the smooth endoplasmic reticulum (lipid droplets, adipose tissue)

Amino Acid Synthesis

• Amino acids are synthesized from intermediates of the citric acid cycle and other metabolic pathways
• Nitrogen is incorporated into amino acids through transamination reactions using glutamate as a nitrogen donor
• Essential amino acids cannot be synthesized by the body and must be obtained from the diet (leucine, isoleucine, valine, lysine)
• Non-essential amino acids can be synthesized from glucose and other precursors (alanine, serine, glycine)
• Amino acids serve as precursors for the synthesis of proteins, neurotransmitters, and other nitrogen-containing compounds (serotonin, dopamine, heme)

Anaplerotic and Cataplerotic Reactions

Anaplerotic Reactions

• Anaplerotic reactions replenish citric acid cycle intermediates that have been withdrawn for biosynthetic purposes
• Maintain the pool of citric acid cycle intermediates to ensure continuous operation of the cycle
• Examples of anaplerotic reactions include pyruvate carboxylase and glutamate dehydrogenase
• Pyruvate carboxylase catalyzes the carboxylation of pyruvate to form oxaloacetate, replenishing the citric acid cycle
• Glutamate dehydrogenase catalyzes the oxidative deamination of glutamate to form α-ketoglutarate, another citric acid cycle intermediate

Cataplerotic Reactions

• Cataplerotic reactions remove excess citric acid cycle intermediates to prevent accumulation
• Maintain the balance of citric acid cycle intermediates and prevent inhibition of the cycle
• Examples of cataplerotic reactions include the malic enzyme and phosphoenolpyruvate carboxykinase
• The malic enzyme catalyzes the oxidative decarboxylation of malate to form pyruvate and NADPH
• Phosphoenolpyruvate carboxykinase catalyzes the decarboxylation of oxaloacetate to form phosphoenolpyruvate, a gluconeogenic precursor

Balancing Anaplerotic and Cataplerotic Reactions

• Anaplerotic and cataplerotic reactions work together to maintain the balance of citric acid cycle intermediates
• Ensure the continuous operation of the citric acid cycle for energy production and biosynthetic purposes
• Imbalances in these reactions can lead to metabolic disorders (pyruvate carboxylase deficiency, malic enzyme deficiency)
• Regulation of these reactions is crucial for maintaining metabolic homeostasis (allosteric regulation, hormonal control)

Amino Acid Metabolism

Amino Acid Catabolism

• Amino acids can be catabolized to generate energy or serve as precursors for gluconeogenesis and ketogenesis
• Transamination reactions transfer the amino group from an amino acid to an α-keto acid, forming a new amino acid and α-keto acid
• Glutamate and α-ketoglutarate are common intermediates in transamination reactions
• Oxidative deamination of glutamate by glutamate dehydrogenase releases ammonia and generates α-ketoglutarate
• The carbon skeletons of amino acids enter the citric acid cycle at various points (acetyl-CoA, α-ketoglutarate, succinyl-CoA, fumarate, oxaloacetate)

Urea Cycle

• The urea cycle is a series of reactions that convert toxic ammonia to urea for excretion
• Occurs primarily in the liver and involves the collaboration of mitochondrial and cytosolic enzymes
• Ammonia is combined with CO2 to form carbamoyl phosphate, which then enters the urea cycle
• Ornithine and citrulline are key intermediates in the urea cycle
• Arginine is cleaved by arginase to release urea and regenerate ornithine
• Defects in urea cycle enzymes can lead to hyperammonemia and neurological damage (ornithine transcarbamylase deficiency)

Amino Acid Disorders

• Amino acid disorders result from defects in amino acid metabolism or transport
• Examples include phenylketonuria (PKU), maple syrup urine disease (MSUD), and homocystinuria
• PKU is caused by a deficiency in phenylalanine hydroxylase, leading to the accumulation of phenylalanine and its toxic metabolites
• MSUD is caused by a deficiency in branched-chain α-keto acid dehydrogenase, leading to the accumulation of branched-chain amino acids (leucine, isoleucine, valine)
• Homocystinuria is caused by a deficiency in cystathionine β-synthase, leading to the accumulation of homocysteine and its toxic effects on the cardiovascular system
• Early diagnosis and dietary management are crucial for preventing the severe consequences of these disorders (newborn screening, low-protein diets)