Question

1) Considering the iterative steps of beta-oxidation of fatty acids, what step is skipped when we encounter a trans-double bond? (biochemistry)

2) Which amino acid is responsible for delivering ammonia equivalents to the liver?

(a) glutamine

(b) aspartate

(c) asparagine

(d) glutamate

3) Describe which part of the pentose phosphate pathway is critical to a population of cells that is rapidly dividing... such as a tumor.

Answer 1

Answer 1) Beta oxidation of fatty acids- additional steps in a trans-double bond

If a double bond is present in an even-numbered carbon (e.g. the second double bond in 18:2, delta 9,12), the generation of trans- double bond instead of cis- creates a problem. Both the activities occur in the mitochondrial matrix in an indirect manner.

1) The three cycles of beta-oxidation occurs and continue normally in the presence of delta 9 double bond through the fourth cycle which produces trans-double bond in the 2-position. This step involves enoyl CoA isomerase. The fourth cycle then completes and fifth cycle begins normally, but proceeds though the acyl CoA dehydrogenase step.

2) 2.4-dienoyl CoA reductase reduces the compound with the help of NADPH + H+ leaving one trans-double bond in the wrong position. This product is a substrate for enoyl isomerse, which is also used for cis-double bond at odd-numbered carbons, which moves the double bond from the 3 to the 2 position. After this step the beta-oxidation occurs normally.

(The chemical reactions are attached as an image)

Answer 2) Option A Glutamine is the correct answer . Glutamine is a storehouse of ammonia and is present in high concentrations in the blood among other amino acids. It serves as a non-toxic storage and transport form of ammonia in the liver. It is synthesized mostly in the liver, brain, and muscle.

Other options are not correct because:

Aspartate: formed from oxaloacetate by transmission from glutamate; Acts as a nitrogen donor in the urea cycle reaction catalyzed by argininosuccinate synthetase in the cytosol. It is a precursor for four amino acids essential in humans.

Asparagine: synthesized from aspartate and glutamine. Three main functions include a) incorporation in the amino acid sequences of the protein, b) storage form of aspartate needed for the synthesis of DNA, RNA, and ATP, c) sources of amino groups for the production of other dispensable amino acids via transaminases.

Glutamate: It is an amino acid that undergoes oxidative deamination to liberate free ammonia for the synthesis of urea. This free amino acid is formed in the peripheral tissues which is transferred to the liver by glutamine for conversion to urea by glucose-alanine cycle.

Answer 3) Important part in pentose phosphate pathway critical for cancer cells

Increasing the glycolytic flux in cancer cells may indirectly affect the non-oxidative pentose phosphate pathway. The elevated glycolytic flux in cancer cells increases the abundance of F6P and G3P which is utilized in the non-oxidative pentose phosphate pathway.

G^PDH is the rate-limiting step which generates the first molecule of NADPH. Tumor cells express relatively very high levels of this enzyme. In terms of activity regulation, NADP+/NADPH ratio is one of the main modulators of the enzyme. NADPH negatively regulates the activity of G6PDH whereas NADP+ is required for the enzyme activity and for its proper conformation. In cancer cells since NADPH consumption is very high the activity of this enzyme is also very high. Hence, this part of PPP is very crucial in cancer cells.