PBIO PART 2

METABOLISM AND PROTEIN

Glycolysis

Intermediate Reaction

Kreb Cycle

Electron Transport Chain

The four Major Pathway for ATP

Cytosol

This is where Glycolysis happen/occur

Embden-Meyerhof Pathway

Other name of Glycolysis

Gudtav Embden

Otto Meyerhof

Jakub Karol Parnas

They discover the Glycolysis Pathway

Enterner-Doudoroff Pathway

The other pathway for Glycolysis

ATP and Pyruvic acid

The end products of Glycolysis

2 pyruvic acid and 6 to 8 ATP

In Glycolysis 1 Glucos is equal to how many ATP and Pyruvic acid?

Aerobic Glycolysis

Anaerobic Glycolysis

The 2 kinds of Glycolysis

Aerobic Glycolysis

- involvement of oxygen; use to convert glucose to pyruvate and ATP, wherein pyruvates are burned for energy, and then converted into fats via fatty acid synthesis; could undergo TCA or KREBSCYCLE

- the final product is pyruvate along with the production of eight ATP molecules

Mitochondria

This is where the Aerobic Glycolysis happen/occur

Anaerobic Glycolysis

- includes ATP production, and has recycled NADH by making the product lactate (muscles)

- the final product is lactate along with the production of two ATP molecules.

Cytoplasm

This is where the Anaerobic Glycolysis happen/occurs

Phorphorylation

Isomerization

Phosphorylation

Formation of Cleavage

Isomerization

Oxidation

Phosphorylation

Isomerization

Dehydration

Process/Steps in Glycolysis

Hexokinase

The enzyme responsible for the phosphorylation in step 1 pf glycolysis and requires Magnesium for its activity.

Glucose-6-Phosphate

Product in Step 1 Phosphorylation in Glycolysis

Fructose-6-Phosphate

The product in step 2 Isomerization

Phosphoglucose Isomerase or Phosphohexose Isomerase

The enzyme responsible in Step 2 Isomerization in Glycolysis

Phosphofructokinase

This enzyme is the responsible for turning friuctose-6-phosphate to fructose-1,6-biphosphate and rate-limiting enzyme; requires Mg2+ion for its activity

Fructose-1,6-Biphosphate

The product in Step 3 Phosphorylation

Aldolase

The responsible enzyme for catalyzing the cleavage of Fructose-1,6- biPO4(FBP) to yield two 3-carbon molecules

Dihydroxyacetone Phosphate (DHAP)

Glyceraldehyde-3-Phosphate (GAP)

The are the two structure that was divided from Fructose-1,6-Biphosphate

Glyceraldehyde-3-Phosphate

The molecule that can already proceed to Glycolytic Pathway after caming from the division of Fructose-1,6-biphosphate.

Triphosphate Isomerase

The enzyme responsible to produce or reorganize Dihydroxyacetone Phosphate to Glyceraldehyde-3-Phosphate.

Triose-phosphate Isomerase

Other name of Triphosphate Isomerase

Glyceraldehyde-3-Phosphate Dehydrogenase

This enzyme that allows NAD to pull the Hydrogen atom off GAP → NADH, producing 3 ATPs. The phosphate groups attack the GAP molecule and release it from the enzyme to yield the final product.

1,3-Biphosphate Glycerate

Product after the Oxidation and Phosphorylation in Glycolysis.

It is an example of a high-energy phosphate group. This is the energy that is used to convert ADP to ATP

Phosphoglycero Kinase

The enzyme responsible for making 1,3-biphosphoglycerate converted to 3-phosphoglycerate

Phosphoglycerate Mutase or Phosphoglyceromutase

The enzyme that rearrange the phosphate group of 3-Phosphoglycerate to be shifted to the 2nd carbon

Enolase or Phosphopyruvate Hydratase

This enzyme convert the 2-phosphoglycerate to phosphoenolpyruvate (PEP)

Pyruvate kinase

The enzyme responsible for the conversion of phosphoenolpyruvate into

pyruvates

Cytosol

NADH is produce from ____

Glycerol Phosphate shuttle

This shuttle can be found in brain and skeletal muscles. 2 electrons are transferred from NADH to dihydroxyacetone PO4(DHAP) with the help of the enzyme glycerophosphate dehydrogenase, resulting a synthesis of 2 ATPs for every cytosolic NADH synthesized

Malate-Aspartate Shuttle

This shuttle can be found in heart, liver, &kidneys. It produces NADH and yields 3 ATPs on each cytosolic matrix oxidized by malate dehydrogenase

Intermediate Reaction

This reaction is mainly for the formation of Acetyl CoA

Aerobic reaction

Anaerobic reaction

The two kinds/types of Intermediate Reaction

Aerobic reaction

→ undergo oxidative decarboxylation of pyruvate

→ ENZYME: Pyruvate dehydrogenase complex

→ PRODUCT: 2 mol of Acetyl CoA that would enter Citric acid cycle or Krebs Cycle (oxidative decarboxylation)

→ Acetyl CoA product is ready for Kreb’s cycle & Fatty Acid

synthesis → PRODUCES 2 Acetyl CoA

Anaerobic reaction

→ WITHOUT the presence of OXYGEN

→ conversion of pyruvic acid/pyruvate to lactic acid

→ ENZYME: lactate dehydrogenase

→ PRODUCT: Lactic acid

Pyruvate dehydrogenase complex

Enzyme in Aerobic reaction

Lactate dehydrogenase

The enzyme in Anaerobic reaction

Tricarboxylic acid cycle or Citric acid cycle

other name of Kreb’s cycle

Kreb Cycle

This is an aerobic pathway because it requires oxygen and the final pathway where the oxidative catabolism of carbohydrates, amino acids, and fatty acids converge their carbon skeleton being converted to CO2. It occurs in Mitochondria in close proximity to ETC to oxidize the reduced co-enzymes NADH and FADH2

Hans Adolf Krebs

The Kreb Cycle is named after him.

Formation of Citrate

Formation of Isocitrate

Oxidation of Isocitrate and Formation of CO₂

Oxidation of Alpha-ketoglutarate andFormationof CO2

Thioester bond cleavage in Succinyl CoAandPhosphorylation of GDP

Oxidation of Succinate

Hydration of Fumarate

Oxidation of L-Malate to Regenerate Oxaloacetate

The steps in Kreb Cycle

Acetyl Coenzyme A

- major fuel for Kreb’s cycle

- derived from oxidative decarboxylationofpyruvate

Alpha-ketoglutarate

- an enzyme very similar to pyruvate dehydrogenase

- activated by CALCIUM and inhibited by NADH & succinyl CoA

Citrate synthase

The enzyme in Step 1: Formation of Citrate of Kreb Cycle

Aconitase

The enzyme in Step 2: Formation of Isocitrate of Kreb Cycle

Isocitrate dehydrogenase

The enzyme in Step 3: Oxidation of Isocitrate and Formationof CO2 producing alpha-kketoglutarate in Kreb Cycle

Alpha-ketoglutarate dehydrogenase complex

The enzyme in Step 4: Oxidation of Alpha-ketoglutarate and Formationof CO2 producing Succinyl CoA in Kreb Cycle

Succinyl Thiokinase or Succinyl Coa Synthetase

The enzyme in Step 5: Thioester bond cleavage in Succinyl CoA and Phosphorylation of GDP to producing succinate and GTP (Guanosine triphosphate) in Kreb Cycle

Succinate dehydrogenase

The enzyme in Step 6: Oxidation of Succinate to Fumate in Kreb Cycle

Fumarase

The enzyme in Step 7: Hydration of Fumarate to Malate in Kreb Cycle

Malate dehydrogenase

The enzyme in Step 8: Oxidation of L-Malate to Regenerate Oxaloacetate in Kreb Cycle

Flavin Adenine Dinucleotide

The spell ouf of FADH₂

Nicotinamide Adenine Dinucleotide

The spell out of NADH

NADH Coenzyme Qreductase

Name of Complex I in Electron Transport Chain

Complex I: NADH Coenzyme Qreductase

- for every 2 electron = 4 protons are pump

- largest protein complex containing 40sub-unitsincluding Flavin mononucleotide (FMN) or Ironsulfurprotein (FeSP)

- received electrons coming fromNADH(fromsugarmetabolism) that will go to ETC to deposit 2 high energy electrons to COMPLEX I; when these small electrons pass through complex they will passthrough a long chain of redox centers (sub-units) andwhen they finally exit complex I it will donate the 2 electrons to a coenzyme Q molecule that will transferit to complex III

Complex II: Succinate–coenzyme Qreductase

- PURPOSE: process the FADH2 fromthecitricacidcycle/Krebs cycle

- smaller consisting 4 sub-units including 2 FeSP- high-energy FADH2 molecules will enter carrying electrons to pass through the redox centersor sub-units inside this complex and when it finally exit from this complex, it will donate them to coenzyme Q that will transfer the electrons to complex III

Succinate–coenzyme Qreductase

Name of Complex II in ETC

Complex III: Coenzyme Q–cytochrome C reductase

- for every 2 electron = 4 protons are pump

- has 11 different sub-units & also includes FeSP and cytochromes

- the electron will enter this complex and will pass through redox centers before reaching cytochrome C that will deliver electrons from this complex to complex IV

Coenzyme Q–cytochrome C reductase

Name of Complex III in ETC

Complex IV: Cytochrome C oxidase

- for every 2 electron = 2 protons are pump

- has 13 sub-units including 2 cytochromes

- end of ETC

- electrons enter, where the 4 electron converts a molecule to Oxygen to produce 2 molecules of water

Cytochrome C oxidase

Name of Complex IV in ETC

Cyanide

Blocks transfer of electronsto O2. Blocks at site III

Antimycin

All intermediates before and including cyt a will be in the reduced state; all

intermediates after and including cyt c1 will be in the oxidized state. Blocks at site II.

Retenone

Blocks oxidation of NADH(site 1). NADH will become reduced; substrates such as succinate that enter via FADH will still be oxidized and make 2 ATPs/mol.

Oligomycin

Block phosphorylation of ADP. Does not inhibit uncoupled oxidations.

Atractyloside and Bongkrekate

Inhibits entry of ADP into mitochondria and ATP export. Stops electrontransport because of lack of ADP. Inside, all ADP is converted to ATP.

Phosphogluvonate Pathway

Other name of Hexose Monophosphate Shunt

Hexose Monophospahte Shunt

NADH is required for the biosynthesis of fatty acid(particularlyNADPH)

PURPOSE of this pathway is It makes NADPH for biosynthesis of fatty acids and riboses for DNA and RNA synthesis

Occurs in the cytosol

- to produce ribose-5-PO4 for nucelotide/DNA synthesis

- to produce NADPH from NADP+ for FA and steroid synthesis,maintaining reduced Gluthathione inside RBC

- to interconvert pentose and hexoses

Enzyme: Glucose-6-PO4 dehydrogenase

Glucuronic Acid Pathway

Other name for Glucose Glucuronic Pathway

Glucose Glucuronic Pathway

Concerned with with the synthesis of glucuronic acid, pentoses & Vitamin C or Ascorbic acid

Quantitatively a minor route of glucose metabolism

Involves the conversion of Glucose-6-PO4 into Glucuronic acid

LIVER is the major tissue performing this function  The enzymes involved are located in the CYTOSOL

NADPH

a reducing agent that is reserved for biosynthetic pathway particularly in the FA synthesis.Thus, HMP shunt is called upon whenre ducing equivalents and fatty acids synthesis is turned on.

It is also used to keep the cellular and mitochondria glutathione in the reduced form through the action of the glutathione reductase

Glucuronic acid

a component of glycosaminoglycans (which is used in the detoxification of non-polar toxic compounds such as bilirubin & steroid hormones)

D-glucornate

- serves as the detoxifying agent for foreign organic cmpds

1. Conversion of GLUCOSE-6-PO4 to UDP glucose

2. Conversion of UDP glucose to UDP glucuronate

3. Unused UDP glucuronate can be converted into a pentose phosphate pathway, which then can be connected to glycolysis through the non-oxidative phase of the HMP shunt

3 stages of Glucose Glucuronic Pathway:

Glycogenesis

The process where in the Glycogen is synthesized from molecules of the alpha-D-glucose

or glucose to glycogen

Location: Cytosol

Hormone responsible: Insulin

Glycogenolysis

Opposite of glycogenesis; lysis or breakdown or the degradation of glycogen or glycogen to glucose

Glycogeneogenesis

Glucose is synthesized from non-carbohydratesubstance(lactate, glycerol, amino acids) proteins, fats, and other sources

Sugar is derived from other sources aside fromglycogen[comesfrom non-carbohydrate substrate e.g. glycerol, lactate, andotherglucogenic amino acids]

Glucose-6- phosphate

Enzyme deficient in Von Gierke’s disease

Lysosomal alpha- glucosidase

Enzyme deficient in Pompe’s disease

Debranching enzyme

Enzyme deficient in Cor’s disease

Branching enzyme

Enzyme deficient in Andersen’s disease

Muscle glycogen phosphorylase

Enzyme deficient in McArdle’s disease

Hepatic/Liver glycogen phosphorylase

Enzyme deficient in Her’s disease

Phosphofructokinase

Enzyme deficient in Tarui’s disease

Proteins

complex, organic nitrogenous substances with very high molecular weights, found in all plant and animal cells, and consisting largely or entirely of alpha-amino acids united in peptide linkage and ythe third major nutrient needed in the body

Proteios

Protein came from greek work ___ means “primary” or “holding first place” or “of first importance”

Amino acid

→ basic unit of proteins joined together by peptidebonds

→ resembles the alphabets

→ total amino acids: 21

1. Enzyme Catalysts

2. Transport storage

3. Coordinated motion

4. Mechanical support

5. Immune protection

6. Generation and Transmission of Nerve

7. Control of Growth and Differentiation

8. Cell signaling

9. Hormones

10. Major components of biological membranes

Biomedical importance of Protein

Simple proteins

This classification of protein is made up of amino acids only

Albumin

- the most abundant protein in human blood plasma, produced by the liver to keep fluid inside blood vessels and carry vital substances.

- soluble in water and dilute aqueous salt soln

- heat-coagulable or coagulated by heat

- dissolve in acids and alkali

Globulins

- a group of essential proteins in the blood that help fight infections, clot blood, and transport nutrients.

- insoluble in water but soluble in aqueous soln

- heat-coagulable

Glutelin

- a major class of water-insoluble plant storage proteins found in the endosperm of grass family seeds like rice, wheat, rye, and barley

- from grass family (ex. Oryzenin - protein found in rice)

- soluble in dilute acids and alkalis

- heat-coagulable

Complete protein

- contains all essential amino acids

- sustain life by itself

- e.g. proteins in milk, meats, and eggs

Incomplete protein

- lack one or more of the essential amino

- cannot sustain life by itself

Prolamine

- a group of plant storage proteins found in cereal grains that dissolve in strong alcohol but not in water

- soluble in alcohol

- ZEIN is a protein from corn

Albuminoid/Sceroprotein

- a major class of structural proteins that are completely insoluble in water, salt solutions, and dilute acids or bases.

- least soluble

- found in exoskeleton structures (hairs and nails)

Histone

- a highly basic, positively charged proteins in eukaryotic and archaeal cell nuclei that act as structural spools to compact and organize chromosomal DNA into repeating units called nucleosomes

- a basic protein

- soluble in water

- found in combination with DNA

Protamine

- simplest or basic protamine

- soluble in water, dilute ammonia, acid, and alkali

- found in spermatozoa