Harper's Illustrated Biochemistry, Volume 1 - Murray R. 1993

Bioenergetics and Carbohydrate and Lipid Metabolism
Intermediary Metabolism
Major Metabolic Pathways

The pattern of tissue METABOLISM is largely determined by Nutrition. In humans and various other mammals, metabolic transformations involve the products absorbed after the Digestion of dietary CARBOHYDRATES, Lipids, and Proteins—predominantly glucose, triacylglycerols, and Amino Acids. In ruminants (and to a lesser extent in other herbivores), Cellulose is digested by symbiotic microorganisms to yield lower homologous organic acids (acetic, propionic, and butyric acids); tissue metabolism in these animals is adapted to utilizing lower Fatty acids as their primary substrate.

Carbohydrate Metabolism (Fig. 16.2)

In all mammals, cellular glucose is converted into Pyruvate and lactate via a metabolic pathway known as Glycolysis. Entry into this pathway requires preliminary phosphorylation. Glycolysis can proceed in the absence of oxygen (anaerobically) when the end product is lactate. Tissues that consume oxygen (aerobic conditions) are capable of converting pyruvate into acetyl-CoA, which can subsequently enter The Citric Acid Cycle. In this cycle, acetyl-CoA is completely oxidized to CO₂ and H₂O, with a major fraction of the process's potential Free energy being conserved as ATP through Oxidative Phosphorylation (Fig.

17.2). Thus, while Glucose serves as the primary fuel for many tissues, it (along with its metabolites) also participates in other processes. 1. Glucose is converted into the polymer Glycogen, which is stored in several tissues, notably Skeletal Muscle and the Liver. 2. The substrate of the Pentose Phosphate Pathway is an intermediate of glycolysis. This pathway provides a source of reducing equivalents (2H) utilized in biosynthetic processes, such as FATTY ACID Biosynthesis, as well as ribose required for the synthesis of NUCLEOTIDES and Nucleic Acids. 3. Triose phosphate, formed at one of the stages of glycolysis, serves as a source of glycerol used in the synthesis of acylglycerols (fats). 4. Pyruvate and several Intermediates of the citric acid cycle provide carbon skeletons for Amino acid synthesis, whereas acetyl-CoA acts as a fundamental building block in the synthesis of long-chain Fatty Acids and Cholesterol—the precursor of all Steroid Hormones synthesized within the body.

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Fig. 16.2. General Overview of carbohydrate metabolism showing the principal end products.

Lipid Metabolism (Fig. 16.3)

Long-chain Fatty acids are derived from de novo synthesis from acetyl-CoA (which in turn originates from carbohydrates) and from dietary lipids. Within tissues, fatty acids can either be oxidized to acetyl-CoA (ß-Oxidation) or esterified into acylglycerols (with triacylglycerols serving as the body's primary energy reserve). The acetyl-CoA generated via ß-oxidation participates in several key processes.

1. Acetyl-CoA can be fully oxidized to CO₂ + H₂O within The Citric Acid cycle. Fatty acids serve as a significant source of energy (tissue fuel) when utilized via ß-oxidation followed by the Reactions of the citric acid cycle.

2. Acetyl-CoA serves as a carbon source for cholesterol.

3. In the liver, it is converted into acetoacetate, the primary ketone body. Ketone Bodies represent an alternative Water-soluble tissue fuel that can become an important energy source under specific conditions, such as starvation.

Amino acid metabolism (Fig. 16.4)

Amino acids are essential for Protein Synthesis. Some of these must be obtained from the diet (Essential Amino Acids) because tissues lack the capacity to synthesize them. The remaining (non-essential) amino acids are also supplied by the diet but can additionally be generated from metabolic intermediates through Transamination—The transfer of amino groups from Other Amino Acids present in excess. Following deamination, excess amino nitrogen is eliminated in the form of urea; the carbon Skeleton remaining after transamination is either oxidized to CO₂ in the citric acid cycle or converted into glucose (Gluconeogenesis) or ketone bodies.

Fig. 16.3. General overview of lipid metabolism showing the principal end products. Ketone bodies include acetoacetate, 3-hydroxybutyrate, and acetone.

Fig. 16.4. General overview of amino acid metabolism showing the principal end products.

In addition to protein synthesis, amino acids serve as precursors for a variety of vital compounds, including Purines, Pyrimidines, and hormones (such as adrenaline and thyroxine).