Biochemistry
Chemistry and Metabolism of Carbohydrates
Carbohydrate metabolism for MBBS: glycolysis, gluconeogenesis, citric acid cycle, HMP shunt, glycogen storage diseases and diabetes cut-offs, mapped to NMC codes BI3.3 to BI3.10.
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Chemistry and Metabolism of Carbohydrates
Carbohydrate metabolism for MBBS: glycolysis, gluconeogenesis, citric acid cycle, HMP shunt, glycogen storage diseases and diabetes cut-offs, mapped to NMC codes BI3.3 to BI3.10.
This chapter covers how the body extracts and stores energy from sugars. It runs through glycolysis, gluconeogenesis, the citric acid cycle, the hexose monophosphate shunt and glycogen metabolism, and links their regulation and enzyme defects to inherited disorders and the laboratory picture of diabetes.
High-yield: Chemistry and Metabolism of Carbohydrates
- Glycolysis converts one glucose to two pyruvate, with a net gain of two ATP and two NADH in the cytosol.
- Phosphofructokinase-1 is the rate-limiting and committed step of glycolysis, activated by fructose-2,6-bisphosphate and AMP, inhibited by ATP and citrate.
- Under anaerobic conditions pyruvate is reduced to lactate to regenerate NAD, allowing glycolysis to continue.
- Gluconeogenesis makes glucose from lactate, glycerol and glucogenic amino acids, using four key enzymes to bypass the irreversible steps of glycolysis.
- Pyruvate carboxylase, the first gluconeogenic bypass enzyme, requires biotin and is activated by acetyl-CoA.
- The pyruvate dehydrogenase complex needs five cofactors: thiamine pyrophosphate, lipoate, coenzyme A, FAD and NAD.
- The citric acid cycle is amphibolic and yields three NADH, one FADH2 and one GTP per acetyl-CoA; isocitrate dehydrogenase is its rate-limiting step.
- The hexose monophosphate shunt generates NADPH for biosynthesis and ribose-5-phosphate for nucleotides; glucose-6-phosphate dehydrogenase is rate-limiting.
- Glucose-6-phosphate dehydrogenase deficiency causes haemolysis with oxidant stress and shows Heinz bodies and bite cells.
- Glycogen synthesis uses glycogen synthase and a branching enzyme; glycogen breakdown uses glycogen phosphorylase and a debranching enzyme.
- Von Gierke disease is glucose-6-phosphatase deficiency causing fasting hypoglycaemia and hepatomegaly; McArdle disease is muscle phosphorylase deficiency.
- Fructose enters glycolysis via fructokinase; aldolase B deficiency causes hereditary fructose intolerance.
- Galactosaemia is classically caused by galactose-1-phosphate uridyltransferase deficiency, presenting with cataracts and liver disease in infancy.
- Fluoride inhibits enolase and arsenate uncouples the substrate-level phosphorylation of glycolysis, both classic metabolic poisons.
- Fasting blood glucose of 126 mg/dL or more, or HbA1c of 6.5% or more, is diagnostic of diabetes mellitus.
Rate-limiting enzymes to remember
- **Glycolysis:** Phosphofructokinase-1. Activated by fructose-2,6-bisphosphate and AMP.
- **Gluconeogenesis:** Fructose-1,6-bisphosphatase (and pyruvate carboxylase, the first bypass).
- **Citric acid cycle:** Isocitrate dehydrogenase.
- **HMP shunt:** Glucose-6-phosphate dehydrogenase. Source of NADPH.
NMC competencies in this chapter
- **BI3.3:** Digestion and assimilation of dietary carbohydrates
- **BI3.4:** Pathways of carbohydrate metabolism: glycolysis, gluconeogenesis, glycogen metabolism and HMP shunt
- **BI3.5:** Regulation and integration of carbohydrate metabolism and associated disorders
- **BI3.6:** The citric acid cycle as an amphibolic pathway and its regulation
- **BI3.7:** Poisons that inhibit key enzymes of carbohydrate metabolism, such as fluoride and arsenate
- **BI3.9:** Mechanism and significance of blood glucose regulation in health and disease
- **BI3.10:** Interpretation of blood glucose and related investigations in carbohydrate disorders
Frequently Asked Questions
What is the rate-limiting step of glycolysis?
Phosphofructokinase-1, which catalyses the committed step. It is activated by fructose-2,6-bisphosphate and AMP and inhibited by ATP and citrate.
Why is the citric acid cycle called amphibolic?
It is both catabolic, oxidising acetyl-CoA to carbon dioxide and reduced coenzymes, and anabolic, since its intermediates feed the synthesis of glucose, amino acids and haem.
What defect causes von Gierke disease?
Deficiency of glucose-6-phosphatase, the enzyme that releases free glucose from the liver. It presents with fasting hypoglycaemia, hepatomegaly and lactic acidosis.
How is diabetes mellitus diagnosed biochemically?
A fasting plasma glucose of 126 mg/dL or more, a two-hour post-load value of 200 mg/dL or more, or an HbA1c of 6.5% or more supports the diagnosis, confirmed on repeat testing.
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