Question

Describe the general pathways and end products of carbohydrate and lipid metabolism in each of the following mammalian tissues: a) Liver b) Adipose c) Muscle (skeletal and heart) d) Brain tissues e) Blood

Answer 1

Answer- Carbohydrate and Lipid metabolism

a) Liver

Hepatocytes are metabolic overachievers in the body. They play critical roles in synthesizing molecules that are utilized elsewhere to support homeostasis, in converting molecules of one type to another, and in regulating energy balances. If you have taken a course in biochemistry, you probably spent most of that class studying metabolic pathways of the liver. At the risk of damning by faint praise, the major metabolic functions of the liver can be summarized into several major categories:

Carbohydrate Metabolism

It is critical for all animals to maintain concentrations of glucose in blood within a narrow, normal range. Maintainance of normal blood glucose levels over both short (hours) and long (days to weeks) periods of time is one particularly important function of the liver.

Hepatocytes house many different metabolic pathways and employ dozens of enzymes that are alternately turned on or off depending on whether blood levels of glucose are rising or falling out of the normal range. Two important examples of these abilities are:

• Excess glucose entering the blood after a meal is rapidly taken up by the liver and sequestered as the large polymer, glycogen (a process called glycogenesis). Later, when blood concentrations of glucose begin to decline, the liver activates other pathways which lead to depolymerization of glycogen (glycogenolysis) and export of glucose back into the blood for transport to all other tissues.
• When hepatic glycogen reserves become exhausted, as occurs when an animal has not eaten for several hours, do the hepatocytes give up? No! They recognize the problem and activate additional groups of enzymes that begin synthesizing glucose out of such things as amino acids and non-hexose carbohydrates (gluconeogenesis). The ability of the liver to synthesize this "new" glucose is of monumental importance to carnivores, which, at least in the wild, have diets virtually devoid of starch.

Fat Metabolism

Few aspects of lipid metabolism are unique to the liver, but many are carried out predominantly by the liver. Major examples of the role of the liver in fat metabolism include:

• The liver is extremely active in oxidizing triglycerides to produce energy. The liver breaks down many more fatty acids that the hepatocytes need, and exports large quantities of acetoacetate into the blood where it can be picked up and readily metabolized by other tissues.
• A bulk of the lipoproteins are synthesized in the liver.
• The liver is the major site for converting excess carbohydrates and proteins into fatty acids and triglyceride, which are then exported and stored in adipose tissue.
• The liver synthesizes large quantities of cholesterol and phospholipids. Some of this is packaged with lipoproteins and made available to the rest of the body. The remainder is excreted in bile as cholesterol or after conversion to bile acids.

b) Adipose: The regulation of lipid and lipoprotein metabolism in the liver is usually integrated with that of adipose tissue and the effectiveness of this relationship is essential for the maintenance of normolipidemic. Together, these tissues represent the poles of a large metabolic cycle in which metabolites of each tissue are used as substrates for the other. Thus, hepatic very low-density lipoprotein (VLDL) is a precursor of triacylglycerols (TAG) stored in adipose tissue, and fatty acids released from adipose tissue TAG are important precursors of hepatic VLDL.

The hydrolysis of triacylglycerol (lipolysis) is under the control of the enzyme “hormone-sensitive triacylglycerol lipase”. This enzyme may exist in one of two forms: An active form ”lipase a” which is phosphorylated, and an inactive form “lipase b” which is dephosphorylated.

Insulin enhances lipogenesis and synthesis of triglycerides by A. It increases transport of glucose into the cell (e.g. in adipose tissue) and stimulates glycolysis

? pyruvic, glycerol 3 PO4, also stimulates HMP to shunt

? NADPH+H+. B. Insulin increase activity of pyruvate dehydrogenase, acetyl-CoA carboxylase and glycerol-phosphate acyltransferase, these three enzymes are regulated by covalent modification i.e. by a phosphorylation-dephosphorylation mechanism.

c) Muscle-

A contemporary view of the reciprocal relationship between carbohydrate and fat oxidation in muscles

Lipolysis is the process in which triacylglycerides (TAGs) are broken down to produce FFAs. Increased FA turnover is triggered by various stimuli, including ?-adrenergic agonists and exercise. FA uptake in the muscle is dependent on metabolic demands and lipid availability. Once inside the cell, FAs enter the oxidative process, TAG synthesis, or if uptake exceeds metabolization, they undergo accumulation in confined compartments, often LD. Acute lipid oversupply produces inhibition of glucose oxidation, and mitochondria preferentially switch from carbohydrate to FA utilization, depicting the high degree of metabolic flexibility in skeletal muscle, In fact, the sole alteration of FA entrance machinery levels is able to modulate FA oxidation rate indicating a high level of metabolic interregulation

d) Brain

Neuronal uptake of FAs remains an important yet poorly understood process. However, it is possible that once FAs have traversed the BBB, FA transporters may also play a key role in facilitating FA uptake into neurons. For example, dissociated neurons from the VMH express both FATP1 and CD36. Specifically, important studies using Fura-2 calcium imaging and fluorometric imaging plate reader membrane potential dye, in addition to pharmacological manipulations have shown that while neurons of the VMH and ARC respond to oleic acid (OA, C18:1 n-9), this response is lost when CD36 is depleted in the VMH using an adeno-associated viral (AAV) vector expressing CD36 short hairpin RNA . Since CD38 is an established gustatory lipid sensor, it is also plausible that other lipid sensors involved in the chemoreception of long-chain fatty acids (LCFAs)/omega-3 fatty acids (?-3 FAs), such as GPR120, are also involved in neuronal lipid sensing. However, although GPR120 is functionally active in immortalized hypothalamic neurons and mediates the anti-inflammatory actions of the ?-3 FA, DHA, its role in neuronal lipid sensing in vivo has not been determined. In addition, FABP3, which is localized in neurons, facilitates brain AA but not palmitic acid (C16:0) uptake and trafficking into specific brain lipid pools .

It is also becoming more widely accepted that neurons may receive metabolic support from glial cells in a variety of forms. The “astrocyte–neuron lactate shuttle” has been postulated, whereby astrocytes metabolize glucose to release lactate, which is then taken up by the neuronally expressed monocarboxylate transporter, providing a supplemental energy source for neurons

e) Blood