CYL456: Chemistry of Life – An Introduction

Biomolecules

Common metabolic pathways

Instructor: Yashveer Singh, PhD

General, Organic, and Biological Chemistry, HS Stoker,

Brooks/Cole

Timberlake’s Chemistry: An Introduction to General, Organic, and

Biological Chemistry, KC Timberlake, Prentice Hall

6 November 2014

Metabolism

Metabolism refers to all biochemical reactions taking place in

living organisms. An average human adult whose weight remains the

same for 40 years processes about 6 tons of solid food and 10,000

gallons of water

The simplest living cells also carry out energy intensive processes

like protein synthesis, DNA replication, RNA transcription, and

membrane transport

Catabolism refers to reaction in which large biochemical

molecules are broken down to smaller ones, usually with the release

of energy (e.g., glucose oxidation)

Anabolism refers to reaction in which small biochemical molecules

are joined together to form larger ones, usually with energy input

(e.g., protein synthesis from amino acids)

Metabolism = catabolism + anabolism

Metabolic reactions in cell usually use series of consecutive

biochemical reactions to convert a starting material into the product,

and hence the term metabolic pathways

Metabolic pathways could be linear or cyclic

Since major metabolic pathways of all life forms are similar, the

term “common metabolic pathways” is used to describe them

Common metabolic pathways

Metabolism and cell structure Most of the energy is

produced in cristae of

mitochondria, hence

the term power house of

cell for mitochondria

Intermediates in metabolic pathways – adenosine

triphosphate (ATP)

ATP is a nucleotide triphosphate and used to store and release

energy

Intermediates in metabolic pathways – adenosine

triphosphate (ATP)

ATP is hydrolyzed to ADP, releasing phosphate group and energy.

ADP can be further hydrolyzed to AMP, releasing another phosphate

group and energy

Phosphate-containing compounds

in metabolic pathways are high-

energy compounds

These compounds have greater

free energy of hydrolysis than other

compounds

Have one or more highly reactive

strained bonds. Energy required to

break strained bonds is

comparatively lower

Difference between the energy

needed to break bonds and that

released during the bond formation

is much higher

Intermediates in metabolic pathways – adenosine

triphosphate (ATP)

Intermediates in metabolic pathways – adenosine

triphosphate (ATP)

Intermediates in metabolic pathways – flavin adenine

dinucleotide (FAD)

FAD is a coenzyme required in metabolic redox reactions

Intermediates in metabolic pathways – flavin adenine

dinucleotide (FAD)

FAD is converted to

FADH2 by accepting

two hydrogen and

two electrons

(reduced). The

process is reversible

and used to generate

double bonds

Intermediates in metabolic pathways – nicotinamide

adenine dinucleotide (NAD+)

NAD+ is a coenzyme required in metabolic redox reactions. It

accepts one hydrogen and converted to NADH. An additional

hydrogen remains in the system and the process is reversible

Intermediates in metabolic pathways – nicotinamide

adenine dinucleotide (NAD+)

NAD+ is

employed to

oxidize

secondary

alcohol to

ketone

Coenzyme A transfers acetyl group in metabolic pathways

Intermediates in metabolic pathways – coenzyme A

(CoA-SH)

Coenzyme A has a free thiol group (-SH), which can be acetylated

(attachment of CH3CO- group) to form acetyl CoA. The acetyl CoA

can be hydrolyzed to release the acetyl group (CH3CO- ) and free

CoA with thiol group

Intermediates in metabolic pathways – coenzyme A

(CoA-SH)

Intermediates in metabolic pathways – a

summary

17

Metabolism: an overview

Digestive tract

Digestion and absorption of carbohydrates

Digestion and absorption of carbohydrates

21 Stoker’s General, Organic, and Biological Chemistry, 5 Ed.

Digestion and absorption of lipids

Triacylglycerols (TAGs) are insoluble in water and water-based

salivary enzymes in the mouth have no effect on them

It undergoes a major physical change. The churning action of the

stomach breaks up triacylglycerol into small globules, or droplets,

which float as a layer above the other components of swallowed

food. This is called chyme

Along with chyme formation, about 10% of TAGs undergo

hydrolysis in the stomach due to the presence of enzyme gastric

lipase

Digestion and absorption of lipids

Arrival of chyme into small intestine triggers the release of bile

(emulsifier) stored in gall bladder through the action of the hormone

cholecystokinin

Bile emulsification action solubilizes the TAG globules and

digestion resumes with the help of enzymes pancreatic lipases,

which hydrolyze ester linkages between the glycerol and fatty acid

units of the TAGs. Complete hydrolysis does not usually occur; only

two of the three fatty acid units are liberated

Bile combines the free fatty acids and monoacylglycerols into

micelles

Digestion and absorption of lipids

Repackaging occurs within the

intestinal cells. The free fatty acids and

monoacyl glycerols are reassembled into

triacylglycerols and combined with

membrane lipids (phospholipids and

cholesterol) and water-soluble proteins to

produce a lipoprotein called a

chylomicron

A chylomicron transports

triacylglycerols- it enters the lymphatic

system through small lymphatic vessels

lining the intestine. It enters the

bloodstream through the thoracic duct (a

large lymphatic vessel just below the

collarbone), where the fluid of the

lymphatic system flows into a vein

Digestion and absorption of lipids

Digestion and absorption of lipids

In blood, TAGs are hydrolyzed to produce glycerol and free fatty

acids by lipoprotein lipases. The fatty acid and glycerol are absorbed

by the cells of the body and are either broken down to acetyl CoA for

energy or stored as lipids

TAG are stored in adipocyte, a TAG-storing cell

Adipose tissues are primarily located beneath the skin, particularly

in the abdominal region, and in areas around vital organs

Adipose cells are among the largest cells in the body and differ

from other cells in that most of the cytoplasm has been replaced

with a large TAG droplet

The hydrolysis and release of fatty acid and glycerol from TAG

in adipocytes is triggered by hormones, like epinephrine and

glucagon. Hormone interacts with membrane receptors and

stimulates production of cAMP using ATP present in adipose cells.

The cAMP activates hormone-sensitive lipase (HSL) through

phosphorylation. HSL hydrolyzes the TAG into fatty acid and

glycerol

The process of tapping the body’s TAG reserves, in adipose tissue,

for energy is called triacylglycerol mobilization

Digestion and absorption of lipids

Digestion and absorption of lipids

Digestion and absorption of lipids

Proteins supply only 10% body’s energy need, and rest comes from

carbohydrates and fats

Protein metabolism

Proteins are denatured in the stomach by the hydrochloric acid

present in gastric juice (pH 1.5-2.0). The enzyme pepsin hydrolyzes

about 10% of peptide bonds in proteins, producing a variety of

polypeptides

Enzyme trypsin, chymotrypsin, and carboxypeptidase in

pancreatic juice further hydrolyzes peptide bonds in small intestine

(pH 7.0-8.0). Aminopeptidase, secreted by intestinal mucosal cells,

also hydrolyzes the bonds

Pepsin, trypsin, chymotrypsin carboxypeptidase, and

aminopeptidase are all examples of proteolytic enzymes, which are

produced in inactive forms (zymogens)

Finally, all amino acids constituting a protein are released and

absorbed through the intestinal wall using active transport process.

Ultimately, the free amino acids enter the bloodstream and distributed

throughout the body

Protein digestion and absorption

Protein digestion and absorption

The amino acid pool is the total supply of free amino acids

available for use in the human body. The three sources of this pool

are (i) dietary proteins; (ii) protein turnover; (iii) and

biosynthesis of amino acids in the liver

Protein turnover is the repetitive process of degrading and re-

synthesizing proteins in the human body

In a healthy individual, the amount of nitrogen taken into the body

(dietary proteins) is similar to the amount of nitrogen excreted from

the body per day. Such a person is said to be in a state of nitrogen

balance

Two types of nitrogen imbalance are known:

Negative nitrogen balance. Protein degradation exceeds protein

synthesis and the amount of nitrogen in the urine exceeds the amount

of nitrogen ingested

Positive nitrogen balance. Rate of protein synthesis exceeds that

of protein degradation

Amino acid utilization

The amino acid are used in following four ways:

Protein synthesis. About 75% of the free amino acids in a healthy

individual is used for protein synthesis, as proteins are always

needed to replace old tissues (protein turnover) and/or to build new

tissue (growth)

Synthesis of non-protein nitrogen-containing compounds.

Amino acids are used for the synthesis of nitrogen-containing

nonprotein compounds (e.g., purines and pyrimidines of nucleic

acids, the heme of hemoglobin, neurotransmitters such as

acetylcholine and serotonin, the choline and ethanolamine of

phosphoglycerides, and hormones such as epinephrine)

Amino acid utilization

Synthesis of nonessential amino acids. The amino acid are used

to produce nonessential amino acids that are in short supply

Production of energy. Excess amino acids cannot be stored and

therefore degraded in the body. The degradation process is different

for each of the 20 amino acids

Amino acid utilization