The below mentioned article provides a short note on the Economics of Carbohydrate and Lipid Metabolism in the whole body.
Glucose is converted to fat under optimal nutritional intake. Except glycerol, fat (as fatty acid) cannot produce glucose due to the irreversibility of the oxidative decarboxylation of pyruvate to acetyl-CoA. Certain tissues are more dependent on the continued supply of glucose than others.
A minimum supply of glucose is necessary in extra hepatic tissues to maintain the integrity of TCA cycle. Glucose is the main source of glycerol-3-phosphate in tissues devoid of glycerokinase. Large quantities of glucose are also required for fetal nutrition and the synthesis of milk.
Certain mechanisms are also involved to safeguard essential supplies of glucose during shortage by allowing other substrates to spare its oxidation.
Ketone bodies and free fatty acids spare the oxidation of glucose in muscle by impairing its entry into the cell, its phosphorylation of glucose-6-phosphate, the phosphofructokinase reaction, and the oxidative decarboxylation of pyruvate. Free fatty acids and ketone bodies oxidation increases the concentration of intracellular citrate which inhibits phosphofructokinase.
Olson has justified that, under carbohydrate shortage, available fuels are oxidized in the following order of preference:
(i) Ketone bodies (and other short chain fatty acids, e.g., acetate)
(ii) Free fatty acids,
(iii) Glucose (shown in Fig. 19.4.).
Under certain conditions, fat mobilization can be reduced by the administration of non-carbohydrate calorigenic substrates. If glucose oxidation is spared by the free fatty acids and ketone bodies, more glucose will be available causing a reduction in output of free fatty acids from adipose tissue and the free fatty acid level of plasma will fall.
The combination of the effects of the free fatty acids in sparing glucose utilization in muscle and heart and the effect of the spared glucose in inhibiting free fatty acid mobilization in adipose tissue has been called the “glucose-fatty acid cycle”.
1. Under fasting condition, glucose concentration becomes less, glycogen is drawn upon to maintain the blood glucose level. Blood insulin level decreases and glucagon level increases. Since the glucose utilization in the adipose tissues decreases and the inhibitory effect of insulin on lipolysis becomes less, fat is mobilized as free fatty acids and glycerol.
The free fatty acids are esterified in the liver and the remainders are oxidized. In the liver and kidney, glycerol joins the carbohydrate pool after being converted to glycerol’s 3- P. The endogenous glucose production cannot keep pace with its utilization and oxidation.
Therefore, the liver glycogen stores become depleted and blood glucose tends to fall. Then fat is mobilized at the increased rate but in several hours the plasma-free fatty acids and the blood glucose stabilize at the fasting level. Hence, increased fatty acid oxidation takes place —resulting in the formation of ketone bodies.
2. The adipose tissues provide carbohydrate in the form of glycerol together with that provided by gluconeogenesis from protein.
3. In prolonged starvation in humans, gluconeogenesis from protein is diminished owing to the diminished release of amino acids, particularly alanine, from muscle. The brain then utilizes ketone bodies in place of glucose.
4. Free fatty acids are under most conditions mobilized in excess of oxidative requirements since a large amount is esterified even during fasting. When the carbohydrate supplies are sufficient, most of the influx is esterified and ultimately re-transported from the liver as VLDL to be utilized by other tissues.
In the case of increased influx of free fatty acids, ketogenesis is available which allows the liver to re-transport much of the influx of free fatty acids in a form which is readily utilized by extra-hepatic tissues under all nutritional conditions.
5. The carbohydrate cycle involves the release of glycerol from adipose tissue and its conversion to glucose in the liver. The lipid cycle involves the release of free fatty acids by adipose tissue, its transport to and esterification in the liver and re-transport of VLDL back to adipose tissue.
These two interrelated cycles are involved during the disturbances in carbohydrate or lipid metabolism where they interact in adipose tissue and in the liver.